Sample records for f-18 choline pet

  1. 18F-choline PET/MRI in suspected recurrence of prostate carcinoma.

    PubMed

    Riola-Parada, C; Carreras-Delgado, J L; Pérez-Dueñas, V; Garcerant-Tafur, M; García-Cañamaque, L

    2018-05-21

    To evaluate the usefulness of simultaneous 18 F-choline PET/MRI in the suspicion of prostate cancer recurrence and to relate 18 F-choline PET/MRI detection rate with analytical and pathological variables. 27 patients with prostate cancer who received local therapy as primary treatment underwent a 18 F-choline PET/MRI due to suspicion of recurrence (persistently rising serum PSA level). 18 F-choline PET/MRI findings were validated by anatomopathological analysis, other imaging tests or by biochemical response to oncological treatment. 18 F-choline PET/MRI detected disease in 15 of 27 patients (detection rate 55.56%). 4 (15%) presented exclusively local recurrence, 5 (18%) lymph node metastases and 7 (26%) bone metastases. Mean PSA (PSA med ) at study time was 2.94ng/mL (range 0.18-10ng/mL). PSA med in patients with positive PET/MRI was 3.70ng/mL (range 0.24-10ng/mL), higher than in patients with negative PET/MRI, PSA med 1.97ng/mL (range 0.18-4.38ng/mL), although without statistically significant differences. Gleason score at diagnosis in patients with a positive study was 7.33 (range 6-9) and in patients with a negative study was 7 (range 6-9), without statistically significant differences. 18 F-choline PET/MRI detection rate was considerable despite the relatively low PSA values in our sample. The influence of Gleason score and PSA level on 18 F-choline PET/MRI detection rate was not statistically significant. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT.

    PubMed

    Ribeiro, Thalles H; S, Raul; Castro, Ana Carolina G; Paulino, Eduardo; Mamede, Marcelo

    2017-02-01

    Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

  3. 68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT

    PubMed Central

    Bluemel, Christina; Krebs, Markus; Polat, Bülent; Linke, Fränze; Eiber, Matthias; Samnick, Samuel; Lapa, Constantin; Lassmann, Michael; Riedmiller, Hubertus; Czernin, Johannes; Rubello, Domenico; Bley, Thorsten; Kropf, Saskia; Wester, Hans-Juergen; Buck, Andreas K.; Herrmann, Ken

    2016-01-01

    Purpose Investigating the value of 68Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative 18F-choline-PET/CT. Patients and Methods One hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an 18F-choline-PET/CT. If negative, an additional 68Ga-PSMA-PET/CTwas offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional 68Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on 18F-choline-PET/CT and those who declined the additional 68Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel). Results The overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for 18F-choline-PET/CT alone. 68Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and 18F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of 68Ga-PSMA-PET/CT in 18F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively. Conclusions The sequential imaging approach designed to limit 68Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. 68Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative 18F-choline PET/CT scans. PMID:26975008

  4. PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

    PubMed

    Calabria, Ferdinando; Chiaravalloti, Agostino; Cicciò, Carmelo; Gangemi, Vincenzo; Gullà, Domenico; Rocca, Federico; Gallo, Gianpasquale; Cascini, Giuseppe Lucio; Schillaci, Orazio

    2017-08-01

    The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body. We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients. 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands. Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a

  5. Evaluation of Prostate Cancer with 11C- and 18F-Choline PET/CT: Diagnosis and Initial Staging.

    PubMed

    Nitsch, Sascha; Hakenberg, Oliver W; Heuschkel, Martin; Dräger, Desiree; Hildebrandt, Guido; Krause, Bernd J; Schwarzenböck, Sarah M

    2016-10-01

    Early diagnosis and adequate staging are crucial for the choice of adequate treatment in prostate cancer (PC). Morphologic and functional imaging modalities, such as CT and MRI, have had limited accuracy in the diagnosis and nodal staging of PC. Molecular PET/CT imaging with 11 C- or 18 F-choline-labeled derivatives is increasingly being used, but its role in the diagnosis and initial staging of PC is controversial because of limitations in sensitivity and specificity for the detection of primary PC. For T staging, functional MRI is superior to 11 C- or 18 F-choline PET/CT. For N staging, 11 C- or 18 F-choline PET/CT can provide potentially useful information that may influence treatment planning. For the detection of bone metastases, 11 C- or 18 F-choline PET/CT has had promising results; however, in terms of cost-effectiveness, the routine use of 11 C- or 18 F-choline PET/CT is still debatable. 11 C- or 18 F-choline PET/CT might be used in high-risk PC before radiation treatment planning, potentially affecting this planning (e.g., regarding dose escalation). This review provides an overview of the diagnostic accuracy and limitations of 11 C- or 18 F-choline PET/CT in the diagnosis and staging of PC. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  6. 3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

    PubMed

    Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

    2007-02-01

    Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

  7. F-18 choline PET does not detect increased metabolism in F-18 fluoroethyltyrosine-negative low-grade gliomas.

    PubMed

    Roelcke, Ulrich; Bruehlmeier, Matthias; Hefti, Martin; Hundsberger, Thomas; Nitzsche, Egbert U

    2012-01-01

    Positron emission tomography (PET) with radiolabeled amino acids provides information on biopsy target and chemotherapy response in patients with low-grade gliomas (LGG). In this article, we addressed whether PET with F-18 choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)-negative LGG patients. Six LGG patients with nongadolinium-enhancing (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of interest were positioned over tumor and contralateral brain. Uptake of FET and CHO was quantified as count ratio of tumor to contralateral brain. The mean FET uptake ratio for FET-negative LGG was 0.95 ± 0.03 (mean ± standard deviation). Five tumors did not show increased uptake ratios for CHO (0.96 ± 0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which, however, was not associated with tumor visualization. Amino acid and choline uptake appear to behave similar in nongadolinium-enhancing LGG. For clinical purposes, CHO PET is not superior to FET PET.

  8. Comparison Between 64Cu-PSMA-617 PET/CT and 18F-Choline PET/CT Imaging in Early Diagnosis of Prostate Cancer Biochemical Recurrence.

    PubMed

    Cantiello, Francesco; Crocerossa, Fabio; Russo, Giorgio Ivan; Gangemi, Vincenzo; Ferro, Matteo; Vartolomei, Mihai Dorin; Lucarelli, Giuseppe; Mirabelli, Maria; Scafuro, Chiara; Ucciero, Giuseppe; De Cobelli, Ottavio; Morgia, Giuseppe; Damiano, Rocco; Cascini, Giuseppe Lucio

    2018-06-04

    To evaluate the diagnostic performance of 64 Cu-PSMA-617 positron emission tomography (PET) with computed tomography (CT) for restaging prostate cancer after biochemical recurrence (BCR) and to compare it with 18 F-choline PET/CT in a per-patient analysis. An observational study was performed of 43 patients with BCR after laparoscopic radical prostatectomy who underwent 64 Cu-PSMA-617 PET/CT and subsequently 18 F-choline PET/CT for restaging. The detection rates (DR) of 64 Cu-PSMA-617 PET/CT and of 18 F-choline PET/CT were calculated by standardized maximum uptake value (SUV max ) at 4 hours and SUV max at 1 hour as reference, respectively. Furthermore, univariate logistic regression analysis was carried out to identify independent predictive factors of positivity with 64 Cu-PSMA-617 PET/CT. An overall positivity with 64 Cu-PSMA-617 PET/CT was found in 32 patients (74.4%) versus 19 (44.2%) with 18 F-choline PET/CT. Specifically, after stratifying for prostate-specific antigen (PSA) values, we found a good performance of 64 Cu-PSMA-617 PET/CT at low PSA levels compared to 18 F-choline PET/CT, with a DR of 57.1% versus 14.3% for PSA 0.2-0.5 ng/mL (P = .031), and of 60% versus 30% with PSA 0.5-1 ng/mL. At univariate binary logistic regression analysis, PSA level was the only independent predictor of 64 Cu-PSMA-617 PET/CT positivity. No significant difference in terms of DR for both 64 Cu-PSMA-617 PET/CT and 18 F-choline PET/CT was found according to different Gleason score subgroups. In our study cohort, a better performance was observed for 64 Cu-PSMA-617 PET/CT compared to 18 F-choline PET/CT in restaging after BCR, especially in patients with low PSA values. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. An Incidental Renal Oncocytoma: 18F-Choline PET/MRI

    PubMed Central

    Mallia, Andrew; Bashir, Usman; Stirling, James; Wolfe, Konrad; Goh, Vicky; Cook, Gary

    2016-01-01

    PET/MRI is a new hybrid imaging modality and has the potential to become a powerful imaging tool. It is currently one of the most active areas of research in diagnostic imaging. The characterisation of an incidental renal lesion can be difficult. In particular, the differentiation of an oncocytoma from other solid renal lesions such as renal cell carcinoma (RCC) represents a diagnostic challenge. We describe the detection of an incidental renal oncocytoma in a 79-year gentleman who underwent a re-staging 18F-Choline PET/MRI following a rise in PSA values (4.07, nadir 1.3).

  10. 18F-Choline PET/CT scan in staging and biochemical recurrence in prostate cancer patients: Changes in classification and radiotherapy planning.

    PubMed

    Cardona Arboniés, J; Rodríguez Alfonso, B; Mucientes Rasilla, J; Martínez Ballesteros, C; Zapata Paz, I; Prieto Soriano, A; Carballido Rodriguez, J; Mitjavila Casanovas, M

    To evaluate the role of the 18 F-Choline PET/CT in prostate cancer management when detecting distant disease in planning radiotherapy and staging and to evaluate the therapy changes guided by PET/TC results. A retrospective evaluation was performed on 18 F-Choline PET/CT scans of patients with prostate cancer. Staging and planning radiotherapy scans were selected in patients with at least 9 months follow up. There was a total of 56 studies, 33 (58.93%) for staging, and 23 (41.07%) for planning radiotherapy. All scans were obtained using a hybrid PET/CT scanner. The PET/CT acquisition protocol consisted of a dual-phase procedure after the administration of an intravenous injection of 296-370MBq of 18 F-Choline. There were 43 out of 56 (76.8%) scans considered as positive, and 13 (23.2%) were negative. The TNM staging was changed in 13 (23.2%) scans. The PET/CT findings ruled out distant disease in 4 out of 13 scans, and unknown distant disease was detected in 9 (69.3%) scans. 18 F-Choline PET/CT is a useful technique for detecting unknown distant disease in prostate cancer when staging and planning radiotherapy. The inclusion of 18 F-choline PET/CT should be considered in prostate cancer management protocols. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  11. 68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT.

    PubMed

    Bluemel, Christina; Krebs, Markus; Polat, Bülent; Linke, Fränze; Eiber, Matthias; Samnick, Samuel; Lapa, Constantin; Lassmann, Michael; Riedmiller, Hubertus; Czernin, Johannes; Rubello, Domenico; Bley, Thorsten; Kropf, Saskia; Wester, Hans-Juergen; Buck, Andreas K; Herrmann, Ken

    2016-07-01

    Investigating the value of Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative F-choline-PET/CT. One hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an F-choline-PET/CT. If negative, an additional Ga-PSMA-PET/CT was offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on F-choline-PET/CT and those who declined the additional Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel). The overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for F-choline-PET/CT alone. Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of Ga-PSMA-PET/CT in F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively. The sequential imaging approach designed to limit Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT scans.

  12. Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results.

    PubMed

    Nanni, Cristina; Schiavina, Riccardo; Boschi, Stefano; Ambrosini, Valentina; Pettinato, Cinzia; Brunocilla, Eugenio; Martorana, Giuseppe; Fanti, Stefano

    2013-07-01

    We assessed the rate of detection rate of recurrent prostate cancer by PET/CT using anti-3-(18)F-FACBC, a new synthetic amino acid, in comparison to that using (11)C-choline as part of an ongoing prospective single-centre study. Included in the study were 15 patients with biochemical relapse after initial radical treatment of prostate cancer. All the patients underwent anti-3-(18)F-FACBC PET/CT and (11)C-choline PET/CT within a 7-day period. The detection rates using the two compounds were determined and the target-to-background ratios (TBR) of each lesion are reported. No adverse reactions to anti-3-(18)F-FACBC PET/CT were noted. On a patient basis, (11)C-choline PET/CT was positive in 3 patients and negative in 12 (detection rate 20%), and anti-3-(18)F-FACBC PET/CT was positive in 6 patients and negative in 9 (detection rate 40%). On a lesion basis, (11)C-choline detected 6 lesions (4 bone, 1 lymph node, 1 local relapse), and anti-3-(18)F-FACBC detected 11 lesions (5 bone, 5 lymph node, 1 local relapse). All (11)C-choline-positive lesions were also identified by anti-3-(18)F-FACBC PET/CT. The TBR of anti-3-(18)F-FACBC was greater than that of (11)C-choline in 8/11 lesions, as were image quality and contrast. Our preliminary results indicate that anti-3-(18)F-FACBC may be superior to (11)C-choline for the identification of disease recurrence in the setting of biochemical failure. Further studies are required to assess efficacy of anti-3-(18)F-FACBC in a larger series of prostate cancer patients.

  13. Impact of time-of-flight PET on quantification accuracy and lesion detection in simultaneous 18F-choline PET/MRI for prostate cancer.

    PubMed

    Mühlematter, Urs J; Nagel, Hannes W; Becker, Anton; Mueller, Julian; Vokinger, Kerstin N; de Galiza Barbosa, Felipe; Ter Voert, Edwin E G T; Veit-Haibach, Patrick; Burger, Irene A

    2018-05-31

    Accurate attenuation correction (AC) is an inherent problem of positron emission tomography magnetic resonance imaging (PET/MRI) systems. Simulation studies showed that time-of-flight (TOF) detectors can reduce PET quantification errors in MRI-based AC. However, its impact on lesion detection in a clinical setting with 18 F-choline has not yet been evaluated. Therefore, we compared TOF and non-TOF 18 F-choline PET for absolute and relative difference in standard uptake values (SUV) and investigated the detection rate of metastases in prostate cancer patients. Non-TOF SUV was significantly lower compared to TOF in all osseous structures, except the skull, in primary lesions of the prostate, and in pelvic nodal and osseous metastasis. Concerning lymph node metastases, both experienced readers detected 16/19 (84%) on TOF PET, whereas on non-TOF PET readers 1 and 2 detected 11 (58%), and 14 (73%), respectively. With TOF PET readers 1 and 2 detected 14/15 (93%) and 11/15 (73%) bone metastases, respectively, whereas detection rate with non-TOF PET was 73% (11/15) for reader 1 and 53% (8/15) for reader 2. The interreader agreement was good for osseous metastasis detection on TOF (kappa 0.636, 95% confidence interval [CI] 0.453-0.810) and moderate on non-TOF (kappa = 0.600, CI 0.438-0.780). TOF reconstruction for 18 F-choline PET/MRI shows higher SUV measurements compared to non-TOF reconstructions in physiological osseous structures as well as pelvic malignancies. Our results suggest that addition of TOF information has a positive impact on lesion detection rate for lymph node and bone metastasis in prostate cancer patients.

  14. Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

    PubMed

    Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

    2017-03-01

    Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV

  15. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial.

    PubMed

    Nanni, Cristina; Zanoni, Lucia; Pultrone, Cristian; Schiavina, Riccardo; Brunocilla, Eugenio; Lodi, Filippo; Malizia, Claudio; Ferrari, Matteo; Rigatti, Patrizio; Fonti, Cristina; Martorana, Giuseppe; Fanti, Stefano

    2016-08-01

    To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse. This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference. In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities

  16. Robustness of Radiomic Features in [11C]Choline and [18F]FDG PET/CT Imaging of Nasopharyngeal Carcinoma: Impact of Segmentation and Discretization.

    PubMed

    Lu, Lijun; Lv, Wenbing; Jiang, Jun; Ma, Jianhua; Feng, Qianjin; Rahmim, Arman; Chen, Wufan

    2016-12-01

    Radiomic features are increasingly utilized to evaluate tumor heterogeneity in PET imaging and to enable enhanced prediction of therapy response and outcome. An important ingredient to success in translation of radiomic features to clinical reality is to quantify and ascertain their robustness. In the present work, we studied the impact of segmentation and discretization on 88 radiomic features in 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) and [ 11 C]methyl-choline ([ 11 C]choline) positron emission tomography/X-ray computed tomography (PET/CT) imaging of nasopharyngeal carcinoma. Forty patients underwent [ 18 F]FDG PET/CT scans. Of these, nine patients were imaged on a different day utilizing [ 11 C]choline PET/CT. Tumors were delineated using reference manual segmentation by the consensus of three expert physicians, using 41, 50, and 70 % maximum standardized uptake value (SUV max ) threshold with background correction, Nestle's method, and watershed and region growing methods, and then discretized with fixed bin size (0.05, 0.1, 0.2, 0.5, and 1) in units of SUV. A total of 88 features, including 21 first-order intensity features, 10 shape features, and 57 second- and higher-order textural features, were extracted from the tumors. The robustness of the features was evaluated via the intraclass correlation coefficient (ICC) for seven kinds of segmentation methods (involving all 88 features) and five kinds of discretization bin size (involving the 57 second- and higher-order features). Forty-four (50 %) and 55 (63 %) features depicted ICC ≥0.8 with respect to segmentation as obtained from [ 18 F]FDG and [ 11 C]choline, respectively. Thirteen (23 %) and 12 (21 %) features showed ICC ≥0.8 with respect to discretization as obtained from [ 18 F]FDG and [ 11 C]choline, respectively. Six features were obtained from both [ 18 F]FDG and [ 11 C]choline having ICC ≥0.8 for both segmentation and discretization, five of which were gray-level co-occurrence matrix

  17. Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

    PubMed

    Chondrogiannis, Sotirios; Marzola, Maria Cristina; Ferretti, Alice; Grassetto, Gaia; Maffione, Anna Margherita; Rampin, Lucia; Fanti, Stefano; Giammarile, Francesco; Rubello, Domenico

    2014-07-01

    To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng

  18. Volumetric modulated arc therapy planning for primary prostate cancer with selective intraprostatic boost determined by 18F-choline PET/CT.

    PubMed

    Kuang, Yu; Wu, Lili; Hirata, Emily; Miyazaki, Kyle; Sato, Miles; Kwee, Sandi A

    2015-04-01

    This study evaluated expected tumor control and normal tissue toxicity for prostate volumetric modulated arc therapy (VMAT) with and without radiation boosts to an intraprostatically dominant lesion (IDL), defined by (18)F-choline positron emission tomography/computed tomography (PET/CT). Thirty patients with localized prostate cancer underwent (18)F-choline PET/CT before treatment. Two VMAT plans, plan79 Gy and plan100-105 Gy, were compared for each patient. The whole-prostate planning target volume (PTVprostate) prescription was 79 Gy in both plans, but plan100-105 Gy added simultaneous boost doses of 100 Gy and 105 Gy to the IDL, defined by 60% and 70% of maximum prostatic uptake on (18)F-choline PET (IDLsuv60% and IDLsuv70%, respectively, with IDLsuv70% nested inside IDLsuv60% to potentially enhance tumor specificity of the maximum point dose). Plan evaluations included histopathological correspondence, isodose distributions, dose-volume histograms, tumor control probability (TCP), and normal tissue complication probability (NTCP). Planning objectives and dose constraints proved feasible in 30 of 30 cases. Prostate sextant histopathology was available for 28 cases, confirming that IDLsuv60% adequately covered all tumor-bearing prostate sextants in 27 cases and provided partial coverage in 1 case. Plan100-105 Gy had significantly higher TCP than plan79 Gy across all prostate regions for α/β ratios ranging from 1.5 Gy to 10 Gy (P<.001 for each case). There were no significant differences in bladder and femoral head NTCP between plans and slightly lower rectal NTCP (endpoint: grade ≥ 2 late toxicity or rectal bleeding) was found for plan100-105 Gy. VMAT can potentially increase the likelihood of tumor control in primary prostate cancer while observing normal tissue tolerances through simultaneous delivery of a steep radiation boost to a (18)F-choline PET-defined IDL. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Gleason score at diagnosis predicts the rate of detection of 18F-choline PET/CT performed when biochemical evidence indicates recurrence of prostate cancer: experience with 1,000 patients.

    PubMed

    Cimitan, Marino; Evangelista, Laura; Hodolič, Marina; Mariani, Giuliano; Baseric, Tanja; Bodanza, Valentina; Saladini, Giorgio; Volterrani, Duccio; Cervino, Anna Rita; Gregianin, Michele; Puccini, Giulia; Guidoccio, Federica; Fettich, Jure; Borsatti, Eugenio

    2015-02-01

    The objective of this study was to explore the ability of the initial Gleason score (GS) to predict the rate of detection of recurrent prostate cancer (PCa) with (18)F-choline PET/CT in a large cohort of patients. Data from 1,000 patients who had undergone (18)F-choline PET/CT because of biochemical evidence of relapse of PCa between 2004 and 2013 were retrieved from databases at 4 centers. Continuous data were compared by the Student t test or ANOVA, and categoric variables were compared by the χ(2) test. Univariable and multivariable analyses were performed by logistic regression. The GS at diagnosis was less than or equal to 6 in 257 patients, 7 in 347 patients, and greater than 7 in 396 patients. The results of 645 PET/CT scans were positive for PCa recurrence. Eighty-one percent of the positive PET/CT results were found in patients with a PSA level of greater than or equal to 2 ng/mL, 43% were found in patients with a PSA level of 1-2 ng/mL, and 31% were found in patients with a PSA level of less than or equal to 1 ng/mL; 78.8% of patients with positive PET/CT results had a GS of greater than 7. The results of (18)F-choline PET/CT scans were negative in 300 patients; 44% had a GS of less than or equal to 6, 35% had a GS of 7, and 17% had a GS of greater than 7. PET/CT results were rated as doubtful in only 5.5% of patients (median PSA, 1.8 ng/mL). When the GS was greater than 7, the rates of detection of (18)F-choline PET/CT were 51%, 65%, and 91% for a PSA level of less than 1 ng/mL, 1-2 ng/mL, and greater than 2 ng/mL, respectively. In univariable and multivariable analyses, both a GS of 7 and a GS of greater than 7 were independent predictors for positive (18)F-choline PET/CT results (odds ratios, 0.226 and 0.330, respectively; P values for both, <0.001). A high GS at diagnosis is a strong predictive factor for positive (18)F-choline PET/CT scan results for recurrent PCa, even when the PSA level is low (i.e., ≤1 ng/mL). © 2015 by the Society of Nuclear

  20. Diagnostic value of combining ¹¹C-choline and ¹⁸F-FDG PET/CT in hepatocellular carcinoma.

    PubMed

    Castilla-Lièvre, Maria-Angéla; Franco, Dominique; Gervais, Philippe; Kuhnast, Bertrand; Agostini, Hélène; Marthey, Lysiane; Désarnaud, Serge; Helal, Badia-Ourkia

    2016-05-01

    In this prospective study, our goal was to emphasize the diagnostic value of combining (11)C-choline and (18)F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease. Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death). Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of (11)C-choline, (18)F-FDG and combined (11)C-choline and (18)F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with (18)F-FDG-positive lesions than those with (18)F-FDG-negative lesions (p < 0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with (18)F-FDG-positive lesions than in those with (18)F-FDG-negative lesions (p < 0.05). The combined use of (11)C-choline and (18)F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.

  1. Influence of hormonal therapy in prostate cancer patients undergoing [18F]fluoromethyl choline PET/CT: a retrospective study.

    PubMed

    Palumbo, Barbara; Sivolella, Silvio; Palumbo, Isabella; Buresta, Tommaso; Radicchia, Valentina; Fravolini, Mario L; Ferretti, Francesca; Bellavita, Rita; Mearini, Luigi; Scialpi, Michele; Aristei, Cynthia; Pelliccia, Gianfranco

    2016-12-01

    Patients with suspected recurrence of prostate cancer undergoing [18F]fluoromethyl choline ([18F]FCH) PET/CT were retrospectively evaluated to investigate the influence of hormonal therapy (HT) in [18F]FCH uptake. [18F]FCH PET/CT was performed in 102 surgically treated patients with suspected recurrence (PSA increase >0.2 ng/mL) of prostate cancer, divided in two groups: under HT (N.=54) and without HT (N.=48) at the time of PET scanning. PET/CT was carried out by an integrated system (Biograph 6, CTI/Siemens, Knoxville, TN, USA) intravenously by administering 4.1 MBq/kg of [18F]FCH to each patient; images were acquired 60 minutes later. On the total number of patients, 66 were found to be true positives (TP), 9 false positives (FP), 5 false negatives (FN) and 22 true negatives (TN), sensitivity to [18F]FCH PET/CT was 93%, specificity 71%, accuracy 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 81%. In the 54 patients under HT, 38 were TP, 6 FP, 3 FN and 7 TN, sensitivity was 93%, specificity 54%, accuracy 83%, PPV 86% and NPV was 70%. In the 48 patients receiving no HT, 28 were TP, 3 FP, 2 FN and 15 TN, sensitivity was 93%, specificity 83%, accuracy 90%, PPV 90% and NPV 88%. A χ2 test showed that sensitivity, accuracy and PPV did not differ among patients with and without HT, while specificity and NPV were significantly lower (P<0.001) in HT treated patients. Sensitivity, accuracy and PPV were similar in patients with and without HT. Specificity and NPV were reduced in patients under HT, but further data are necessary to support if this reduction is casual or related to therapy and it could be confirmed in a larger series of patients.

  2. F-18 Choline PET angiography of the pelvic arteries: evaluation of image quality and comparison with contrast-enhanced CT.

    PubMed

    Freesmeyer, Martin; Drescher, Robert

    2015-01-01

    The purpose was to show the feasibility of F-18 choline positron emission tomography (PET) angiography for the evaluation of abdominal and iliac arteries. Thirty-five patients were examined and image quality was scored. Findings were correlated with contrast-enhanced computed tomography. Image quality was best in the aorta and common iliac arteries (100% and 93% of vessels). Negative predictive values of PET angiography were excellent (100%), and positive predictive values were impaired by disease overestimation. PET angiography is technically feasible and of good image quality in large arteries. In selected cases, it may become an alternative to established angiographic methods. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Compartmental model of 18F-choline

    NASA Astrophysics Data System (ADS)

    Janzen, T.; Tavola, F.; Giussani, A.; Cantone, M. C.; Uusijärvi, H.; Mattsson, S.; Zankl, M.; Petoussi-Henß, N.; Hoeschen, C.

    2010-03-01

    The MADEIRA Project (Minimizing Activity and Dose with Enhanced Image quality by Radiopharmaceutical Administrations), aims to improve the efficacy and safety of 3D functional imaging by optimizing, among others, the knowledge of the temporal variation of the radiopharmaceuticals' uptake in and clearance from tumor and healthy tissues. With the help of compartmental modeling it is intended to optimize the time schedule for data collection and improve the evaluation of the organ doses to the patients. Administration of 18F-choline to screen for recurrence or the occurrence of metastases in prostate cancer patients is one of the diagnostic applications under consideration in the frame of the project. PET and CT images have been acquired up to four hours after injection of 18F-choline. Additionally blood and urine samples have been collected and measured in a gamma counter. The radioactivity concentration in different organs and data of plasma clearance and elimination into urine were used to set-up a compartmental model of the biokinetics of the radiopharmaceutical. It features a central compartment (blood) exchanging with organs. The structure describes explicitly liver, kidneys, spleen, plasma and bladder as separate units with a forcing function approach. The model is presented together with an evaluation of the individual and population kinetic parameters, and a revised time schedule for data collection is proposed. This optimized time schedule will be validated in a further set of patient studies.

  4. Dose-escalation using intensity-modulated radiotherapy for prostate cancer - evaluation of quality of life with and without (18)F-choline PET-CT detected simultaneous integrated boost.

    PubMed

    Pinkawa, Michael; Piroth, Marc D; Holy, Richard; Klotz, Jens; Djukic, Victoria; Corral, Nuria Escobar; Caffaro, Mariana; Winz, Oliver H; Krohn, Thomas; Mottaghy, Felix M; Eble, Michael J

    2012-01-30

    In comparison to the conventional whole-prostate dose escalation, an integrated boost to the macroscopic malignant lesion might potentially improve tumor control rates without increasing toxicity. Quality of life after radiotherapy (RT) with vs. without (18)F-choline PET-CT detected simultaneous integrated boost (SIB) was prospectively evaluated in this study. Whole body image acquisition in supine patient position followed 1 h after injection of 178-355MBq (18)F-choline. SIB was defined by a tumor-to-background uptake value ratio > 2 (GTV(PET)). A dose of 76Gy was prescribed to the prostate (PTV(prostate)) in 2Gy fractions, with or without SIB up to 80Gy. Patients treated with (n = 46) vs. without (n = 21) SIB were surveyed prospectively before (A), at the last day of RT (B) and a median time of two (C) and 19 month (D) after RT to compare QoL changes applying a validated questionnaire (EPIC - expanded prostate cancer index composite). With a median cut-off standard uptake value (SUV) of 3, a median GTV(PET) of 4.0 cm(3) and PTV(boost) (GTV(PET) with margins) of 17.3 cm(3) was defined. No significant differences were found for patients treated with vs. without SIB regarding urinary and bowel QoL changes at times B, C and D (mean differences ≤3 points for all comparisons). Significantly decreasing acute urinary and bowel score changes (mean changes > 5 points in comparison to baseline level at time A) were found for patients with and without SIB. However, long-term urinary and bowel QoL (time D) did not differ relative to baseline levels - with mean urinary and bowel function score changes < 3 points in both groups (median changes = 0 points). Only sexual function scores decreased significantly (> 5 points) at time D. Treatment planning with (18)F-choline PET-CT allows a dose escalation to a macroscopic intraprostatic lesion without significantly increasing toxicity.

  5. [18F]Fluoromethyl-[1,2-2H4]-choline: A novel radiotracer for imaging choline metabolism in tumors by positron emission tomography

    PubMed Central

    Leyton, Julius; Smith, Graham; Zhao, Yongjun; Perumal, Meg; Nguyen, Quang-De; Robins, Edward; Årstad, Erik; Aboagye, Eric O.

    2009-01-01

    Current radiotracers for positron emission tomography (PET) imaging of choline metabolism have poor systemic metabolic stability in vivo. We describe a novel radiotracer, [18F]fluoromethyl-[1,2-2H4]-choline (D4-FCH), that employs deuterium isotope effect to improve metabolic stability. D4-FCH proved more resistant to oxidation than its non-deuterated analog, [18F]fluoromethylcholine (FCH), in plasma, kidneys, liver and tumor, while retaining phosphorylation potential. Tumor radiotracer levels, a determinant of sensitivity in imaging studies, was improved by deuterium substitution; tumor uptake values expressed as %injected dose/voxel at 60 min were 7.43 ± 0.47 and 5.50 ± 0.49 for D4-FCH and FCH, respectively, (P = 0.04). D4-FCH was also found to be a useful response biomarker. Treatment with the mitogenic extracellular kinase inhibitor, PD0325901, resulted in a reduction in tumor radiotracer uptake that occurred in parallel with reductions in choline kinase A expression. In conclusion, D4-FCH is a very promising metabolically stable radiotracer for imaging choline metabolism in tumors. PMID:19773436

  6. Thoracic staging in lung cancer: prospective comparison of 18F-FDG PET/MR imaging and 18F-FDG PET/CT.

    PubMed

    Heusch, Philipp; Buchbender, Christian; Köhler, Jens; Nensa, Felix; Gauler, Thomas; Gomez, Benedikt; Reis, Henning; Stamatis, Georgios; Kühl, Hilmar; Hartung, Verena; Heusner, Till A

    2014-03-01

    Therapeutic decisions in non-small cell lung cancer (NSCLC) patients depend on the tumor stage. PET/CT with (18)F-FDG is widely accepted as the diagnostic standard of care. The purpose of this study was to compare a dedicated pulmonary (18)F-FDG PET/MR imaging protocol with (18)F-FDG PET/CT for primary and locoregional lymph node staging in NSCLC patients using histopathology as the reference. Twenty-two patients (12 men, 10 women; mean age ± SD, 65.1 ± 9.1 y) with histopathologically confirmed NSCLC underwent (18)F-FDG PET/CT, followed by (18)F-FDG PET/MR imaging, including a dedicated pulmonary MR imaging protocol. T and N staging according to the seventh edition of the American Joint Committee on Cancer staging manual was performed by 2 readers in separate sessions for (18)F-FDG PET/CT and PET/MR imaging, respectively. Results from histopathology were used as the standard of reference. The mean and maximum standardized uptake value (SUV(mean) and SUV(max), respectively) and maximum diameter of the primary tumor was measured and compared in (18)F-FDG PET/CT and PET/MR imaging. PET/MR imaging and (18)F-FDG PET/CT agreed on T stages in 16 of 16 of patients (100%). All patients were correctly staged by (18)F-FDG PET/CT and PET/MR (100%), compared with histopathology. There was no statistically significant difference between (18)F-FDG PET/CT and (18)F-FDG PET/MR imaging for lymph node metastases detection (P = 0.48). For definition of thoracic N stages, PET/MR imaging and (18)F-FDG PET/CT were concordant in 20 of 22 patients (91%). PET/MR imaging determined the N stage correctly in 20 of 22 patients (91%). (18)F-FDG PET/CT determined the N stage correctly in 18 of 22 patients (82%). The mean differences for SUV(mean) and SUV(max) of NSCLC in (18)F-FDG PET/MR imaging and (18)F-FDG PET/CT were 0.21 and -5.06. These differences were not statistically significant (P > 0.05). The SUV(mean) and SUV(max) measurements derived from (18)F-FDG PET/CT and (18)F-FDG PET

  7. 18F-fluorocholine PET-guided target volume delineation techniques for partial prostate re-irradiation in local recurrent prostate cancer.

    PubMed

    Wang, Hui; Vees, Hansjörg; Miralbell, Raymond; Wissmeyer, Michael; Steiner, Charles; Ratib, Osman; Senthamizhchelvan, Srinivasan; Zaidi, Habib

    2009-11-01

    We evaluate the contribution of (18)F-choline PET/CT in the delineation of gross tumour volume (GTV) in local recurrent prostate cancer after initial irradiation using various PET image segmentation techniques. Seventeen patients with local-only recurrent prostate cancer (median=5.7 years) after initial irradiation were included in the study. Rebiopsies were performed in 10 patients that confirmed the local recurrence. Following injection of 300 MBq of (18)F-fluorocholine, dynamic PET frames (3 min each) were reconstructed from the list-mode acquisition. Five PET image segmentation techniques were used to delineate the (18)F-choline-based GTVs. These included manual delineation of contours (GTV(man)) by two teams consisting of a radiation oncologist and a nuclear medicine physician each, a fixed threshold of 40% and 50% of the maximum signal intensity (GTV(40%) and GTV(50%)), signal-to-background ratio-based adaptive thresholding (GTV(SBR)), and a region growing (GTV(RG)) algorithm. Geographic mismatches between the GTVs were also assessed using overlap analysis. Inter-observer variability for manual delineation of GTVs was high but not statistically significant (p=0.459). In addition, the volumes and shapes of GTVs delineated using semi-automated techniques were significantly higher than those of GTVs defined manually. Semi-automated segmentation techniques for (18)F-choline PET-guided GTV delineation resulted in substantially higher GTVs compared to manual delineation and might replace the latter for determination of recurrent prostate cancer for partial prostate re-irradiation. The selection of the most appropriate segmentation algorithm still needs to be determined.

  8. Detection of osseous metastasis by 18F-NaF/18F-FDG PET/CT versus CT alone.

    PubMed

    Sampath, Srinath C; Sampath, Srihari C; Mosci, Camila; Lutz, Amelie M; Willmann, Juergen K; Mittra, Erik S; Gambhir, Sanjiv S; Iagaru, Andrei

    2015-03-01

    Sodium fluoride PET (18F-NaF) has recently reemerged as a valuable method for detection of osseous metastasis, with recent work highlighting the potential of coadministered 18F-NaF and 18F-FDG PET/CT in a single combined imaging examination. We further examined the potential of such combined examinations by comparing dual tracer 18F-NaF18/F-FDG PET/CT with CT alone for detection of osseous metastasis. Seventy-five participants with biopsy-proven malignancy were consecutively enrolled from a single center and underwent combined 18F-NaF/18F-FDG PET/CT and diagnostic CT scans. PET/CT as well as CT only images were reviewed in blinded fashion and compared with the results of clinical, imaging, or histological follow-up as a truth standard. Sensitivity of the combined 18F-NaF/18F-FDG PET/CT was higher than that of CT alone (97.4% vs 66.7%). CT and 18F-NaF/18F-FDG PET/CT were concordant in 73% of studies. Of 20 discordant cases, 18F-NaF/18F-FDG PET/CT was correct in 19 (95%). Three cases were interpreted concordantly but incorrectly, and all 3 were false positives. A single case of osseous metastasis was detected by CT alone, but not by 18F-NaF/18F-FDG PET/CT. Combined 18F-NaF/18F-FDG PET/CT outperforms CT alone and is highly sensitive and specific for detection of osseous metastases. The concordantly interpreted false-positive cases demonstrate the difficulty of distinguishing degenerative from malignant disease, whereas the single case of metastasis seen on CT but not PET highlights the need for careful review of CT images in multimodality studies.

  9. [(18)F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results.

    PubMed

    Pasqualetti, Francesco; Panichi, Marco; Sainato, Aldo; Matteucci, Fabrizio; Galli, Luca; Cocuzza, Paola; Ferrazza, Patrizia; Coraggio, Gabriele; Pasqualetti, Giuseppe; Derosa, Lisa; Sollini, Martina; Mannelli, Lorenzo; Ortori, Simona; Monzani, Fabio; Ricci, Sergio; Greco, Carlo; Fabrini, Maria Grazia; Erba, Paola Anna

    2016-01-22

    A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [(18)F]Choline ([(18)F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [(18)F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [(18)F]FMCHPET/CT. A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. Repeated salvage [(18)F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.

  10. Cancer Localization in the Prostate with F-18 Fluorocholine Positron Emission Tomography. Addendum

    DTIC Science & Technology

    2010-01-01

    of malignancy in anatomical sextants of the prostate gland. The rationale for evaluating fluorocholine as an oncologic tracer applicable to...interest in radiolabeled choline deriv- atives as oncologic tracers for positron emission tomogra- phy (PET) [6, 7]. This approach has shown feasibility in...prostate cancer using the tracer fluorine-18 fluor- omethylcholine (18F-choline) [8–11]. As a preliminary step in evaluating 18F-choline PET/CT as a

  11. Combined early dynamic (18)F-FDG PET/CT and conventional whole-body (18)F-FDG PET/CT provide one-stop imaging for detecting hepatocellular carcinoma.

    PubMed

    Wang, Shao-Bo; Wu, Hu-Bing; Wang, Quan-Shi; Zhou, Wen-Lan; Tian, Ying; Li, Hong-Sheng; Ji, Yun-Hai; Lv, Liang

    2015-06-01

    It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (P<0.05). ED (18)F-FDG PET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P<0.001 and P>0.05, respectively). One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

    PubMed

    Chen, Wei; Cloughesy, Timothy; Kamdar, Nirav; Satyamurthy, Nagichettiar; Bergsneider, Marvin; Liau, Linda; Mischel, Paul; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

    2005-06-01

    3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0

  13. Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma.

    PubMed

    Valentini, Maria Consuelo; Mellai, Marta; Annovazzi, Laura; Melcarne, Antonio; Denysenko, Tetyana; Cassoni, Paola; Casalone, Cristina; Maurella, Cristiana; Grifoni, Silvia; Fania, Piercarlo; Cistaro, Angelina; Schiffer, Davide

    2017-10-31

    Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value ( 18 F-FDG SUV max ), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable. 18 F-FDG SUV max , Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables. Combined MRI and 18 F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB.

  14. Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma

    PubMed Central

    Valentini, Maria Consuelo; Mellai, Marta; Annovazzi, Laura; Melcarne, Antonio; Denysenko, Tetyana; Cassoni, Paola; Casalone, Cristina; Maurella, Cristiana; Grifoni, Silvia; Fania, Piercarlo; Cistaro, Angelina; Schiffer, Davide

    2017-01-01

    Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value (18F-FDG SUVmax), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable. 18F-FDG SUVmax, Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables. Combined MRI and 18F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB. PMID:29207673

  15. [18F]Fluorocholine PET/CT Imaging of Liver Cancer: Radiopathologic Correlation with Tissue Phospholipid Profiling.

    PubMed

    Kwee, Sandi A; Sato, Miles M; Kuang, Yu; Franke, Adrian; Custer, Laurie; Miyazaki, Kyle; Wong, Linda L

    2017-06-01

    [ 18 F]fluorocholine PET/CT can detect hepatocellular carcinoma (HCC) based on imaging the initial steps of phosphatidylcholine synthesis. To relate the diagnostic performance of [ 18 F]fluorocholine positron emission tomography (PET)/x-ray computed tomography (CT) to the phospholipid composition of liver tumors, radiopathologic correspondence was performed in patients with early-stage liver cancer who had undergone [ 18 F]fluorocholine PET/CT before tumor resection. Tumor and adjacent liver were profiled by liquid chromatography mass spectrometry, quantifying phosphatidylcholine species by mass-to-charge ratio. For clinical-radiopathologic correlation, HCC profiles were reduced to two orthogonal principal component factors (PCF1 and PCF2) accounting for 80 % of total profile variation. Tissues from 31 HCC patients and 4 intrahepatic cholangiocarcinoma (ICC) patients were analyzed, revealing significantly higher levels of phosphocholine, CDP-choline, and highly saturated phosphatidylcholine species in HCC tumors relative to adjacent liver and ICC tumors. Significant loading values for PCF1 corresponded to phosphatidylcholines containing poly-unsaturated fatty acids while PCF2 corresponded only to highly saturated phosphatidylcholines. Only PCF2 correlated significantly with HCC tumor-to-liver [ 18 F]fluorocholine uptake ratio (ρ = 0.59, p < 0.0005). Sensitivity for all tumors based on an abnormal [ 18 F]fluorocholine uptake ratio was 93 % while sensitivity for HCC based on increased tumor [ 18 F]fluorocholine uptake was 84 %, with lower levels of highly saturated phosphatidylcholines in tumors showing low [ 18 F]fluorocholine uptake. Most HCC tumors contain high levels of saturated phosphatidylcholines, supporting their dependence on de novo fatty acid metabolism for phospholipid membrane synthesis. While [ 18 F]fluorocholine PET/CT can serve to identify these lipogenic tumors, its imperfect diagnostic sensitivity implies metabolic heterogeneity across HCC

  16. [18F]fluorocholine PET/CT imaging of liver cancer: radiopathologic correlation with tissue phospholipid profiling

    PubMed Central

    Kwee, Sandi A; Sato, Miles M; Kuang, Yu; Franke, Adrian; Custer, Laurie; Miyazaki, Kyle; Wong, Linda L

    2017-01-01

    BACKGROUND [18F]fluorocholine PET/CT can detect hepatocellular carcinoma (HCC) based on imaging the initial steps of phosphatidylcholine synthesis. To relate the diagnostic performance of [18F]fluorocholine PET/CT to the phospholipid composition of liver tumors, radiopathologic correspondence was performed in patients with early-stage liver cancer who had undergone [18F]fluorocholine PET/CT before tumor resection. METHODS Tumor and adjacent liver were profiled by liquid chromatography mass spectrometry, quantifying phosphatidylcholine species by mass-to-charge ratio. For clinical-radiopathologic correlation, HCC profiles were reduced to two orthogonal principal component factors (PCF1 and PCF2) accounting for 80% of total profile variation. RESULTS Tissues from 31 HCC patients and 4 intrahepatic cholangiocarcinoma (ICC) patients were analyzed, revealing significantly higher levels of phosphocholine, CDP-choline, and highly-saturated phosphatidylcholine species in HCC tumors relative to adjacent liver and ICC tumors. Significant loading values for PCF1 corresponded to phosphatidylcholines containing poly-unsaturated fatty acids while PCF2 corresponded only to highly-saturated phosphatidylcholines. Only PCF2 correlated significantly with HCC tumor-to-liver [18F]fluorocholine uptake ratio (ρ = 0.59, p < 0.0005). Sensitivity for all tumors based on an abnormal [18F]fluorocholine uptake ratio was 93%, while sensitivity for HCC based on increased tumor [18F]fluorocholine uptake was 84%, with lower levels of highly-saturated phosphatidylcholines in tumors showing low [18F]fluorocholine uptake. CONCLUSION Most HCC tumors contain high levels of saturated phosphatidylcholines, supporting their dependence on de-novo fatty acid metabolism for phospholipid membrane synthesis. While [18F]fluorocholine PET/CT can serve to identify these lipogenic tumors, its imperfect diagnostic sensitivity implies metabolic heterogeneity across HCC and a weaker lipogenic phenotype in some

  17. Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment.

    PubMed

    Richter, José A; Rodríguez, Macarena; Rioja, Jorge; Peñuelas, Iván; Martí-Climent, Josep; Garrastachu, Puy; Quincoces, Gemma; Zudaire, Javier; García-Velloso, María J

    2010-04-01

    The purpose of this study was to evaluate a dual tracer 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) and (11)C-choline positron emission tomography (PET) protocol in the detection of biochemical prostate cancer relapse. Seventy-three patients (median Prostate Specific Antigen (PSA) Test value 2.7 ng/ml (1.1-5.4)) after radical treatment. PET scans were performed by means of a ECAT-Exact HR+ in the first 18 patients and in a PET/computed tomography Biograph II in the remaining 55 patients. The sensitivity of (11)C-choline and FDG was 60.6% and 31%. In PSA levels over 1.9 ng/ml, sensitivity increased to 80% and 40%, respectively. In the group receiving adjuvant hormone therapy, the diagnostic yields were 71.2% and 43%, respectively. While (11)C-choline-PET could not differentiate well and poorly differentiated Gleason score patients, FDG-PET results were almost significant (p = 0.058). A PSA value higher than 1.9 ng/ml determines a significant increase in the diagnostic yield. Adjuvant hormonotherapy has no influence on the PET results. FDG has a better correlation with the Gleason score than (11)C-choline.

  18. Recent Developments of 18F-FET PET in Neuro-oncology.

    PubMed

    Muoio, Barbara; Giovanella, Luca; Treglia, Giorgio

    2017-11-23

    From the past decade to date several studies about O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) positron emission tomography (PET) in brain tumours have been published in the literature. Objective The aim of this narrative review is to summarize the recent developments and the current role of 18F-FET PET in brain tumours according to recent literature data. Methods Main findings from selected recently published and relevant articles on the role of 18F-FET PET in neuro-oncology were described. Results 18F-FET PET may be useful in the differential diagnosis between brain tumours and non-neoplastic lesions and between low-grade and high-grade gliomas. Integration of 18F-FET PET into surgical planning allows better delineation of the extent of resection beyond margins visible with standard MRI. For biopsy planning, 18F-FET PET is particularly useful in identifying malignant foci within non-contrast-enhancing gliomas. 18F-FET PET may improve the radiation therapy planning in patients with gliomas. This metabolic imaging method may be useful to evaluate treatment response in patients with gliomas and it improves the differential diagnosis between brain tumours recurrence and post-treatment changes. 18F-FET PET may provide useful prognostic information in high-grade gliomas. Conclusions Based on recent literature data 18F-FET PET may provide additional diagnostic information compared to standard MRI in neuro-oncology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model.

    PubMed

    Liu, Ren-Shyan; Chou, Ta-Kai; Chang, Chih-Hsien; Wu, Chun-Yi; Chang, Chi-Wei; Chang, Tsui-Jung; Wang, Shih-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

    2009-04-01

    2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), [(18)F]fluoroacetate ([(18)F]FAc) and [(18)F]fluoromisonidazole ([(18)F]FMISO) were all considered to be positron emission tomography (PET) probes for tumor diagnosis, though based on different rationale of tissue uptake. This study compared the biodistribution, pharmacokinetics and imaging of these three tracers in a sarcoma- and inflammation-bearing mouse model. C3H mice were inoculated with 2x10(5) KHT sarcoma cells in the right thigh on Day 0. Turpentine oil (0.1 ml) was injected in the left thigh on Day 11 to induce inflammatory lesion. Biodistribution, pharmacokinetics and microPET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc were performed on Day 14 after tumor inoculation. The inflammatory lesions were clearly visualized by [(18)F]FDG/microPET and autoradiography at 3 days after turpentine oil injection. The tumor-to-muscle and inflammatory lesion-to-muscle ratios derived from microPET imaging were 6.79 and 1.48 for [(18)F]FMISO, 8.12 and 4.69 for [(18)F]FDG and 3.72 and 3.19 for [(18)F]FAc at 4 h post injection, respectively. Among these, the tumor-to-inflammation ratio was the highest (4.57) for [(18)F]FMISO compared with that of [(18)F]FDG (1.73) and [(18)F]FAc (1.17), whereas [(18)F]FAc has the highest bioavailability (area under concentration of radiotracer vs. time curve, 116.2 hxpercentage of injected dose per gram of tissue). MicroPET images and biodistribution studies showed that the accumulation of [(18)F]FMISO in the tumor is significantly higher than that in inflammatory lesion at 4 h post injection. [(18)F]FDG and [(18)F]FAc delineated both tumor and inflammatory lesions. Our results demonstrated the potential of [(18)F]FMISO/PET in distinguishing tumor from inflammatory lesion.

  20. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma.

    PubMed

    Beuthien-Baumann, B; Strumpf, A; Zessin, J; Bredow, J; Kotzerke, J

    2007-10-01

    In patients with medullary thyroid carcinoma (MTC), rising levels of the tumour markers calcitonin and CEA after primary surgery indicate tumour recurrence or metastases. The only chance of cure is the resection of localised tumour tissue. For positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) and (18)F-dihydroxyphenylalanine ((18)F-DOPA), sensitivities of 78% and 63% have been reported, but in a considerable percentage of MTC patients the source of tumour marker elevation is not detected. The aim of this retrospective data evaluation was to compare the value of PET with (18)F-FDG, (18)F-DOPA and the amino acid tracer 3-O-methyl-6-[(18)F]fluoro-DOPA ((18)F-OMFD) in the detection of MTC recurrence. Fifteen patients with elevated calcitonin were investigated with PET as part of their individual clinical work-up. All patients underwent (18)F-FDG PET and (18)F-DOPA PET, and ten patients underwent (18)F-OMFD PET. With (18)F-FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, (18)F-DOPA revealed suspicious foci; five of these seven patients showed partially corresponding uptake of (18)F-FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were verified. With (18)F-OMFD, a small focus in the liver was suspected in one patient without a correlate on (18)F-FDG PET, (18)F-DOPA PET or conventional imaging. (18)F-FDG and (18)F-DOPA showed foci that were highly suspicious for local recurrence or metastasis of MTC, although histological verification in these patients with numerous previous surgical interventions was performed in only two patients. The amino acid tracer (18)F-OMFD had no diagnostic impact in these patients.

  1. Optimizing a 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer

    PubMed Central

    Simoncic, Urban; Perlman, Scott; Liu, Glenn; Jeraj, Robert

    2015-01-01

    Background The 18F-NaF/18F-FDG cocktail PET/CT imaging has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castrate-resistant prostate cancer (mCRPC). Materials and methods Study was done on 6 patients with mCRPC that had analyzed a total of 26 lesions. Patients had 18F-NaF and 18F-FDG injections separated in time. Dynamic PET/CT imaging recorded uptake time course for both tracers into osseous metastases. 18F-NaF and 18F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of 18F-NaF and 18F-FDG Standardized Uptake Value (SUV) images. Peak, mean and total SUVs were evaluated for both tracers and all visible lesions. The 18F-NaF/18F-FDG cocktail was optimized under the assumption that contribution of both tracers to the image formation should be equal. SUV images for combined 18F-NaF/18F-FDG cocktail PET/CT imaging were generated for cocktail compositions with 18F-NaF:18F-FDG ratio varying from 1:8 to 1:2. Results The 18F-NaF peak and mean SUVs were on average 4-5 times higher than the 18F-FDG peak and mean SUVs, with inter-lesion coefficient-of-variations (COV) of 20%. 18F-NaF total SUV was on average 7 times higher than the 18F-FDG total SUV. When the 18F-NaF:18F-FDG ratio changed from 1:8 to 1:2, typical SUV on generated PET images increased by 50%, while change in uptake visual pattern was hardly noticeable. Conclusion The 18F-NaF/18F-FDG cocktail has equal contributions of both tracers to the image formation when the 18F-NaF:18F-FDG ratio is 1:5. Therefore we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the 18F-NaF/18F-FDG cocktail composition in any 18F-NaF/18F-FDG cocktail PET/CT exams. PMID:26378490

  2. Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer.

    PubMed

    Peterson, Lanell M; O'Sullivan, Janet; Wu, Qian Vicky; Novakova-Jiresova, Alena; Jenkins, Isaac; Lee, Jean H; Shields, Andrew; Montgomery, Susan; Linden, Hannah M; Gralow, Julie R; Gadi, Vijayakrishna K; Muzi, Mark; Kinahan, Paul E; Mankoff, David A; Specht, Jennifer M

    2018-05-10

    Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18 F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18 F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18 F-FDG PET and 18 F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18 F-FDG PET and 18 F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUV max and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18 F-FDG PET and 18 F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE ( P = <0.001) and TTP ( P = 0.044). Higher FDG SUV max at scan2 predicted a shorter time to tSRE ( P = <0.001). A multivariable model using FDG SUV max of the index lesion at scan1 plus the difference in SUV max of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by 18 F-FDG PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) ( P = 0.007, 0.028 respectively), with a trend toward improved survival ( P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18 F-NaF PET was associated with longer OS ( P = 0.027). Conclusion: Changes in 18 F-FDG PET parameters

  3. Predictive factors of 18F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

    PubMed

    Johnson, Alison C; Dugué, Audrey Emmanuelle; Silva, Marlon; Moise, Laura; Tillou, Xavier; Joly, Florence; Aide, Nicolas

    2016-12-01

    The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with 18 F-choline (CH) PET/CT after external beam radiation therapy (EBRT). In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent 18 F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA. Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence. In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt). 18 F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups. We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive

  4. Fully automated SPE-based synthesis and purification of 2-[18F]fluoroethyl-choline for human use.

    PubMed

    Schmaljohann, Jörn; Schirrmacher, Esther; Wängler, Björn; Wängler, Carmen; Schirrmacher, Ralf; Guhlke, Stefan

    2011-02-01

    2-[(18)F]Fluoroethyl-choline ([(18)F]FECH) is a promising tracer for the detection of prostate cancer as well as brain tumors with positron emission tomography (PET). [(18)F]FECH is actively transported into mammalian cells, becomes phosphorylated by choline kinase and gets incorporated into the cell membrane after being metabolized to phosphatidylcholine. So far, its synthesis is a two-step procedure involving at least one HPLC purification step. To allow a wider dissemination of this tracer, finding a purification method avoiding HPLC is highly desirable and would result in easier accessibility and more reliable production of [(18)F]FECH. [(18)F]FECH was synthesized by reaction of 2-bromo-1-[(18)F]fluoroethane ([(18)F]BFE) with dimethylaminoethanol (DMAE) in DMSO. We applied a novel and very reliable work-up procedure for the synthesis of [(18)F]BFE. Based on a combination of three different solid-phase cartridges, the purification of [(18)F]BFE from its precursor 2-bromoethyl-4-nitrobenzenesulfonate (BENos) could be achieved without using HPLC. Following the subsequent reaction of the purified [(18)F]BFE with DMAE, the final product [(18)F]FECH was obtained as a sterile solution by passing the crude reaction mixture through a combination of two CM plus cartridges and a sterile filter. The fully automated synthesis was performed using as well a Raytest SynChrom module (Raytest, Germany) or a Scintomics HotboxIII module (Scintomics, Germany). The radiotracer [(18)F]FECH can be synthesized in reliable radiochemical yields (RCY) of 37±5% (Synchrom module) and 33±5% (Hotbox III unit) in less than 1 h using these two fully automated commercially available synthesis units without HPLC involvement for purification. Detailed quality control of the final injectable [(18)F]FECH solution proved the high radiochemical purity and the absence of Kryptofix2.2.2, DMAE and DMSO used in the course of synthesis. Sterility and bacterial endotoxin testing following standard

  5. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

    PubMed

    Fu, Yilong; Ong, Lai-Chun; Ranganath, Sudhir H; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K H; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials.

  6. A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model

    PubMed Central

    Ranganath, Sudhir H.; Zheng, Lin; Kee, Irene; Zhan, Wenbo; Yu, Sidney; Chow, Pierce K. H.; Wang, Chi-Hwa

    2016-01-01

    Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 ± 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/ 18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID:26844770

  7. Fluorine-18 NaF PET imaging of child abuse.

    PubMed

    Drubach, Laura A; Sapp, Mark V; Laffin, Stephen; Kleinman, Paul K

    2008-07-01

    We describe the use of 18F-NaF positron emission tomography (PET) whole-body imaging for the evaluation of skeletal trauma in a case of suspected child abuse. To our knowledge, 18F NaF PET has not been used in the past for the evaluation of child abuse. In our patient, this technique detected all sites of trauma shown by initial and follow-up skeletal surveys, including bilateral metaphyseal fractures of the proximal humeri. Fluorine-18 NaF PET has potential advantage over Tc-99m-labeled methylene diphosphonate (MDP) based upon superior image contrast and spatial resolution.

  8. Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients.

    PubMed

    Johnbeck, Camilla B; Knigge, Ulrich; Langer, Seppo W; Loft, Annika; Berthelsen, Anne Kiil; Federspiel, Birgitte; Binderup, Tina; Kjaer, Andreas

    2016-12-01

    Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18 F-FLT PET as a prognostic marker for NENs in comparison with 18 F-FDG PET and Ki-67 index. One hundred patients were PET-scanned with both 18 F-FLT and 18 F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18 F-FLT uptake was also investigated. Thirty-seven percent of patients had a positive 18 F-FLT PET scan, and 49% had 18 F-FDG PET-positive foci. Patients with a high 18 F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18 F-FLT uptake. No correlation was found between Ki-67 index and 18 F-FLT uptake. In a multivariate analysis 18 F-FLT, 18 F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18 F-FDG and Ki-67 remained significant. 18 F-FLT PET has prognostic value in NEN patients but when 18 F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18 F-FLT PET only adds information regarding PFS but not OS, whereas 18 F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18 F-FLT in addition to 18 F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18 F-FLT PET in NENs remains to be established. © 2016 by the Society of Nuclear Medicine and Molecular

  9. Evaluation of the Outcome of Lung Nodules Missed on 18F-FDG PET/MRI Compared with 18F-FDG PET/CT in Patients with Known Malignancies.

    PubMed

    Sawicki, Lino M; Grueneisen, Johannes; Buchbender, Christian; Schaarschmidt, Benedikt M; Gomez, Benedikt; Ruhlmann, Verena; Umutlu, Lale; Antoch, Gerald; Heusch, Philipp

    2016-01-01

    The lower detection rate of (18)F-FDG PET/MRI than (18)F-FDG PET/CT regarding small lung nodules should be considered in the staging of malignant tumors. The purpose of this study was to evaluate the outcome of these small lung nodules missed by (18)F-FDG PET/MRI. Fifty-one oncologic patients (mean age ± SD, 56.6 ± 14.0 y; 29 women, 22 men; tumor stages, I [n = 7], II [n = 7], III [n = 9], IV [n = 28]) who underwent (18)F-FDG PET/CT and subsequent (18)F-FDG PET/MRI on the same day were retrospectively enrolled. Images were analyzed by 2 interpreters in random order and separate sessions with a minimum of 4 wk apart. A maximum of 10 lung nodules was identified for each patient on baseline imaging. The presence, size, and presence of focal tracer uptake was noted for each lung nodule detected on (18)F-FDG PET/CT and (18)F-FDG PET/MRI using a postcontrast T1-weighted 3-dimensional gradient echo volume-interpolated breath-hold examination sequence with fat suppression as morphologic dataset. Follow-up CT or (18)F-FDG PET/CT (mean time to follow-up, 11 mo; range, 3-35 mo) was used as a reference standard to define each missed nodule as benign or malignant based on changes in size and potential new tracer uptake. Nodule-to-nodule comparison between baseline and follow-up was performed using descriptive statistics. Out of 134 lung nodules found on (18)F-FDG PET/CT, (18)F-FDG PET/MRI detected 92 nodules. Accordingly, 42 lung nodules (average size ± SD, 3.9 ± 1.3 mm; range, 2-7 mm) were missed by (18)F-FDG PET/MRI. None of the missed lung nodules presented with focal tracer uptake on baseline imaging or follow-up (18)F-FDG PET/CT. Thirty-three out of 42 missed lung nodules (78.6%) in 26 patients were rated benign, whereas 9 nodules (21.4%) in 4 patients were rated malignant. As a result, 1 patient required upstaging from tumor stage I to IV. Although most small lung nodules missed on (18)F-FDG PET/MRI were found to be benign, there was a relevant number of undetected

  10. Relationship Between Clinicopathological Characteristics and PET/CT Uptake in Esophageal Squamous Cell Carcinoma: [18F]Alfatide versus [18F]FDG.

    PubMed

    Dong, Yinjun; Wei, Yuchun; Chen, Guanxuan; Huang, Yong; Song, Pingping; Liu, Shuguang; Zheng, Jinsong; Cheng, Monica; Yuan, Shuanghu

    2018-06-04

    To assess a novel radiotracer aluminum [ 18 F]fluoride-1,4,7-triazacyclononane-triacetic acid-pegylated dimeric RGD ([ 18 F]ALF-NOTA-PRGD 2 , denoted as [ 18 F]Alfatide) for positron emission tomography (PET)/X-ray computed tomography (CT) and explore the relationships between clinicopathological characteristics and maximum standard uptake values in primary (SUV P ) and metastatic lymph nodes (SUV LN ) of patients with esophageal squamous cell carcinoma (ESCC), as verified by pathologic examination and compared with those obtained with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]DG) PET. We prospectively enrolled patients with newly diagnosed ESCC who agreed to undergo [ 18 F]Alfatide PET/CT or [ 18 F]FDG PET/CT scans before surgery at Shandong Cancer Hospital from May 2011 to July 2017. SUVs and the pathological tumor-node-metastasis (pTNM) stages of primary tumors and metastatic lymph nodes (LNs) were measured and confirmed pathologically. Immunohistochemical (IHC) staining for integrin αvβ3 was performed on tumor samples (both primary tumors and metastatic LNs) collected from nine patients. Of 61 patients who underwent PET/CT scans, 46 then underwent curative surgery and were included in our analysis (n = 21 for [ 18 F]Alfatide PET/CT and n = 25 for [ 18 F]FDG PET/CT). No significant differences in the SUV P on [ 18 F]Alfatide PET/CT or [ 18 F]FDG PET/CT were observed among the cohorts according to gender, pathological stage, T stage, status of LNs, and differentiation (all P > 0.05). The SUV LN differed significantly between the pathological stages and status of LNs both on [ 18 F]Alfatide PET/CT (P = 0.03, 0.003) and [ 18 F]FDG PET/CT (P = 0.001. < 0.001), but not according to gender (P = 0.128, 0.129), T stage (P = 0.791, 0.727), or tumor differentiation (P = 0.049, 0.053). Significant positive correlations were observed between the SUV LN on [ 18 F]Alfatide PET/CT and [ 18 F]FDG PET/CT, and pathological stage (r = 0

  11. PET Tracer 18F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models.

    PubMed

    Oka, Shuntaro; Kanagawa, Masaru; Doi, Yoshihiro; Schuster, David M; Goodman, Mark M; Yoshimura, Hirokatsu

    2017-01-01

    18 F-Fluciclovine ( trans -1-amino-3- 18 F-fluorocyclobutanecarboxylic acid; anti - 18 F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14 C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3 H-2-deoxy-2-fluoro-D-glucose ( 3 H-FDG), 3 H-choline chloride ( 3 H-choline), and 99m Tc-hydroxymethylene diphosphonate ( 99m Tc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14 C-fluciclovine, 3 H-FDG, and 3 H-choline, but not 99m Tc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99m Tc-HMDP accumulated mostly in osteoblastic lesions. 14 C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14 C-fluciclovine and 3 H-FDG existed, based on histological differences: low 14 C-fluciclovine and high 3 H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14 C-fluciclovine was not clear, yet clearer than with 3 H-FDG. Although half of the osteoblastic lesions with 14 C-fluciclovine accumulation showed negligible 3 H-choline accumulation in comparison, they were histologically similar to lesions with marked 14 C-fluciclovine and 3 H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and

  12. PET Tracer 18F-Fluciclovine Can Detect Histologically Proven Bone Metastatic Lesions: A Preclinical Study in Rat Osteolytic and Osteoblastic Bone Metastasis Models

    PubMed Central

    Oka, Shuntaro; Kanagawa, Masaru; Doi, Yoshihiro; Schuster, David M.; Goodman, Mark M.; Yoshimura, Hirokatsu

    2017-01-01

    18F-Fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid; anti-18F-FACBC) is a positron emission tomography (PET) tracer for diagnosing cancers (e.g., prostate and breast cancer). The most frequent metastatic organ of these cancers is bone. Fluciclovine-PET can visualize bony lesions in clinical practice; however, such lesions have not been described histologically. Methods: We investigated the potential of 14C-fluciclovine in aiding the visualization of osteolytic and osteoblastic bone metastases (with histological analyses), compared with 3H-2-deoxy-2-fluoro-D-glucose (3H-FDG), 3H-choline chloride (3H-choline), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) by using triple-tracer autoradiography in rat breast cancer osteolytic (on day 12 ± 1 postinjection of MRMT-1) and prostate cancer osteoblastic (on day 20 ± 3 postinjection of AT6.1) metastatic models. Results: The distribution patterns of 14C-fluciclovine, 3H-FDG, and 3H-choline, but not 99mTc-HMDP, were similar in both models, and the lesions where these tracers accumulated were, histologically, typical osteolytic and osteoblastic lesions. 99mTc-HMDP accumulated mostly in osteoblastic lesions. 14C-fluciclovine could visualize the osteolytic lesions as early as day 6 postinjection of MRMT-1. However, differential distributions in 14C-fluciclovine and 3H-FDG existed, based on histological differences: low 14C-fluciclovine and high 3H-FDG accumulation in osteolytic lesions with inflammation. In the osteoblastic metastatic model, visualization of osteoblastic lesions with 14C-fluciclovine was not clear, yet clearer than with 3H-FDG. Although half of the osteoblastic lesions with 14C-fluciclovine accumulation showed negligible 3H-choline accumulation in comparison, they were histologically similar to lesions with marked 14C-fluciclovine and 3H-choline accumulation. Conclusion: These results suggest that fluciclovine-PET can visualize true osteolytic and osteoblastic bone metastatic lesions

  13. Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using 18F-fluoromisonidazole PET/CT: a pilot study.

    PubMed

    Supiot, Stéphane; Rousseau, Caroline; Dore, Mélanie; Cheze-Le-Rest, Catherine; Kandel-Aznar, Christine; Potiron, Vincent; Guerif, Stéphane; Paris, François; Ferrer, Ludovic; Campion, Loïc; Meingan, Philippe; Delpon, Gregory; Hatt, Mathieu; Visvikis, Dimitris

    2018-02-09

    Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of 18 F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment. Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and 18 F-choline-PET. 18 F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation. Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUV max and SUV max tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml. This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.

  14. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine

    PubMed Central

    Vali, Reza; Loidl, Wolfgang; Pirich, Christian; Langesteger, Werner; Beheshti, Mohsen

    2015-01-01

    While 18F-Fluorodeoxyglucose (18F-FDG) Positron-Emission Tomography (PET) has limited value in prostate cancer (PCa), it may be useful for specific subgroups of PCa patients with hormone-resistant poorly differentiated cell types. 18F-Fluorocholine (18F-FCH) PET/CT has been increasingly used in primary and recurrent PCa and has been shown to add valuable information. Although there is a correlation between the foci of activity and the areas of malignancy in the prostate gland, the clinical value of 18F-FCH is still controversial for detection of the malignant focus in the prostate. For the T-staging of PCa at diagnosis the value of 18F-FCH is limited. This is probably due to limited resolution of PET system and positive findings in benign prostate diseases. Conversely, 18F-FCH PET/CT is a promising imaging modality for the delineation of local and distant nodal recurrence and bone metastases and is poised to have an impact on therapy management. In this review, recent studies of 18F-FCH PET/CT in PCa are summarized. PMID:25973332

  15. Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

    PubMed

    Huber, G F; Hüllner, M; Schmid, C; Brunner, A; Sah, B; Vetter, D; Kaufmann, P A; von Schulthess, G K

    2018-06-01

    To assess the additional diagnostic value of 18 F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18 F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. A total of 26 patients underwent 18 F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. These results demonstrate that 18 F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

  16. {sup 18}F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    D'Angelillo, Rolando M., E-mail: r.dangelillo@unicampus.it; Sciuto, Rosa; Ramella, Sara

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up tomore » total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.« less

  17. Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study.

    PubMed

    Derlin, Thorsten; Tóth, Zoltán; Papp, László; Wisotzki, Christian; Apostolova, Ivayla; Habermann, Christian R; Mester, Janos; Klutmann, Susanne

    2011-07-01

    Formation and progression of atherosclerotic plaque is a dynamic and complex process involving various pathophysiologic steps including inflammation and calcification. The purpose of this study was to compare macrophage activity as determined by (18)F-FDG PET and ongoing mineral deposition as measured by (18)F-sodium fluoride PET in atherosclerotic plaque and to correlate these findings with calcified plaque burden as assessed by CT. Forty-five patients were examined by whole-body (18)F-FDG PET, (18)F-sodium fluoride PET, and CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio [TBR]). The pattern of tracer uptake in atherosclerotic lesions was compared after color-coded multistudy image fusion of PET and CT studies. The Fisher exact test and the Spearman correlation coefficient r(s) were used for statistical analysis of image-based results and cardiovascular risk factors. Intra- and interrater reproducibility were evaluated using the Cohen κ. (18)F-sodium fluoride uptake was observed at 105 sites in 27 (60%) of the 45 study patients, and mean TBR was 2.3 ± 0.7. (18)F-FDG uptake was seen at 124 sites in 34 (75.6%) patients, and mean TBR was 1.5 ± 0.3. Calcified atherosclerotic lesions were observed at 503 sites in 34 (75.6%) patients. Eighty-one (77.1%) of the 105 lesions with marked (18)F-sodium fluoride uptake and only 18 (14.5%) of the 124 lesions with (18)F-FDG accumulation were colocalized with arterial calcification. Coincident uptake of both (18)F-sodium fluoride and (18)F-FDG was observed in only 14 (6.5%) of the 215 arterial lesions with radiotracer accumulation. PET/CT with (18)F-FDG and (18)F-sodium fluoride may allow evaluation of distinct pathophysiologic processes in atherosclerotic lesions and might provide information on the complex interactions involved in formation and progression of atherosclerotic plaque.

  18. 18F-FDOPA PET/CT imaging of MAX-related pheochromocytoma.

    PubMed

    Taïeb, David; Jha, Abhishek; Guerin, Carole; Pang, Ying; Adams, Karen T; Chen, Clara C; Romanet, Pauline; Roche, Philippe; Essamet, Wassim; Ling, Alexander; Quezado, Martha M; Castinetti, Frédéric; Sebag, Fréderic; Pacak, Karel

    2018-03-08

    MYC associated factor X (MAX) has been recently described as a new susceptibility pheochromocytoma (PHEO) gene with a total of approximately 40 reported cases. At present, no study has specifically described the functional imaging phenotype of MAX-related PHEO. The objective of this study was to present our experience with contrast-enhanced CT and 18F-FDOPA PET/CT imaging in 6 consecutive patients (4 at initial diagnosis and 2 at follow-up evaluation) with rare but clinically important MAX-related PHEOs. In 5 patients, 18F-FDOPA was also compared to other radiopharmaceuticals. Patients had 5 different mutations in the MAX gene that caused disruption of Max/Myc interaction and/or abolished interaction with DNA based on in-silico analyses. All but one patient developed bilateral PHEOs during their lifetime. In all cases, 18F-FDOPA PET/CT accurately visualized PHEOs that were often multiple within the same gland or bilateral and detected more adrenal and extradrenal lesions than CT (per lesion sensitivity 90.5% vs 52.4% for CT/MRI). The 2 missed PHEO on 18F-FDOPA PET/CT were <1cm, corresponding to nodular adrenomedullary hyperplasia. 68Ga-DOTATATE PET/CT detected fewer lesions than 18F-FDOPA PET/CT in 1/3 patients and 18F-FDG PET/CT was only faintly positive in 2/4 patients with underestimation of extraadrenal lesions in 1 patient. MAX-related PHEO exihibit a marked 18F-FDOPA uptake, a finding that illustrates the common well-differentiated chromaffin pattern of PHEO associated with activation of kinase signaling pathways. 18F-FDOPA PET/CT should be considered as the first-line functional imaging modality for diagnostic or follow-up evaluation in these patients.

  19. Integrated whole-body PET/MR imaging with 18F-FDG, 18F-FDOPA, and 18F-fluorodopamine in paragangliomas, in comparison to PET/CT: NIH first clinical experience with a single-injection, dual-modality imaging protocol

    PubMed Central

    Blanchet, Elise M.; Millo, Corina; Martucci, Victoria; Maass-Moreno, Roberto; Bluemke, David A.; Pacak, Karel

    2017-01-01

    Purpose Paragangliomas (PGLs) are tumors that can metastasize and recur; therefore, lifelong imaging follow-up is required. Hybrid positron emission tomography (PET)/computed tomography (/CT) is an essential tool to image PGLs. Novel hybrid PET/magnetic resonance (/MR) scanners are currently being studied in clinical oncology. We studied the feasibility of simultaneous whole-body PET/MR imaging to evaluate patients with PGLs. Methods Fifty-three PGLs or PGL-related lesions from eight patients were evaluated. All patients underwent a single-injection, dual-modality imaging protocol consisting of a PET/CT and subsequent PET/MR scan. Four patients were evaluated with 18F-fluorodeoxyglucose (18F-FDG), two with 18F-fluorodihydroxyphenylalanine (18F-FDOPA), and two with 18F-fluorodopamine (18F-FDA). PET/MR data were acquired using a hybrid whole-body 3-Tesla integrated PET/MR scanner. PET and MR data (DIXON images for attenuation correction and T2-weighted sequences for anatomic allocation) were acquired simultaneously. Imaging workflow and imaging times were documented. PET/MR and PET/CT data were visually assessed (blindly) in regards to image quality, lesion detection, and anatomic allocation and delineation of the PET findings. Results With hybrid PET/MR, we obtained high quality images in an acceptable acquisition time (median: 31 min, range: 25–40 min) with good patient compliance. A total of 53 lesions, located in the head-and-neck area (6), mediastinum (2), abdomen and pelvis (13), lungs (2), liver (4), and bone (26) were evaluated. 51 lesions were detected with PET/MR and confirmed by PET/CT. Two bone lesions (L4 body (8 mm) and sacrum (6 mm)) were not detectable on an 18F-FDA scan PET/MR, likely due to washout of the 18F-FDA. Co-registered MR tended to be superior to co-registered CT for head-and-neck, abdomen, pelvis, and liver lesions for anatomic allocation and delineation. Conclusions Clinical PGL evaluation with hybrid PET/MR is feasible with high image

  20. Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

    PubMed

    Mathieu, Cédric; Ferrer, Ludovic; Carlier, Thomas; Colombié, Mathilde; Rusu, Daniela; Kraeber-Bodéré, Françoise; Campion, Loic; Rousseau, Caroline

    2015-01-01

    Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status. Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis. The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively). Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of

  1. Diagnostic performance of a streamlined 18F-choline PET-CT protocol for the detection of prostate carcinoma recurrence in combination with appropriate-use criteria.

    PubMed

    Frood, R; Baren, J; McDermott, G; Bottomley, D; Patel, C; Scarsbrook, A

    2018-04-30

    To evaluate the efficacy of single time-point half-body (skull base to thighs) fluorine-18 choline positron emission tomography-computed tomography (PET-CT) compared to a triple-phase acquisition protocol in the detection of prostate carcinoma recurrence. Consecutive choline PET-CT studies performed at a single tertiary referral centre in patients with biochemical recurrence of prostate carcinoma between September 2012 and March 2017 were reviewed retrospectively. The indication for the study, imaging protocol used, imaging findings, whether management was influenced by the PET-CT, and subsequent patient outcome were recorded. Ninety-one examinations were performed during the study period; 42 were carried out using a triple-phase protocol (dynamic pelvic imaging for 20 minutes after tracer injection, half-body acquisition at 60 minutes and delayed pelvic scan at 90 minutes) between 2012 and August 2015. Subsequently following interim review of diagnostic performance, a streamlined protocol and appropriate-use criteria were introduced. Forty-nine examinations were carried out using the single-phase protocol between 2015 and 2017. Twenty-nine (69%) of the triple-phase studies were positive for recurrence compared to 38 (78%) of the single-phase studies. Only one patient who had a single-phase study would have benefited from a dynamic acquisition, they have required no further treatment or imaging and are currently under prostate-specific antigen (PSA) surveillance. Choline PET-CT remains a useful tool for the detection of prostate recurrence when used in combination with appropriate-use criteria. Removal of dynamic and delayed acquisition phases reduces study time without adversely affecting accuracy. Benefits include shorter imaging time which improves patient comfort, reduced cost, and improved scanner efficiency. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  2. Advances in PET myocardial perfusion imaging: F-18 labeled tracers.

    PubMed

    Rischpler, Christoph; Park, Min-Jae; Fung, George S K; Javadi, Mehrbod; Tsui, Benjamin M W; Higuchi, Takahiro

    2012-01-01

    Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.

  3. The role of 18F-FDOPA and 18F-FDG-PET in the management of malignant and multifocal phaeochromocytomas.

    PubMed

    Taïeb, D; Tessonnier, L; Sebag, F; Niccoli-Sire, P; Morange, I; Colavolpe, C; De Micco, C; Barlier, A; Palazzo, F F; Henry, J F; Mundler, O

    2008-10-01

    (18)F-DOPA has emerged as a promising tool in the localization of chromaffin-tissue-derived tumours. Interestingly, phaeochromocytomas (PHEO) are also FDG avid. The aim of this study was to retrospectively evaluate the results of (18)F-FDOPA and/or (18)F-FDG-PET in patients with PHEO and paragangliomas (PGLs) and to compare the outcome of this approach with the traditional therapeutic work-up. Nine patients with non-MEN2 related PHEO or PGL were evaluated. At the time of the PET studies, the patients were classified into three groups based on their clinical history, conventional and SPECT imaging. The groups were malignant disease (n = 5, 1 VHL), apparently unique tumour site in patients with previous surgery (n = 1, SDHB) and multifocal tumours (n = 3, 1 VHL, 1 SDHD). (18)F-FDOPA and (18)F-FDG-PET PET/CT were then performed in all patients. PET successfully identified additional tumour sites in five out of five patients with metastatic disease that had not been identified with SPECT + CI. Whilst tumour tracer uptake varied between patients it exhibited a consistently favourable residence time for delayed acquisitions. (18)F-FDOPA uptake (SUVmax) was superior to (18)F-FDG uptake in cases of neck PGL (three patients, four tumours). If only metastatic forms and abdominal PGLs were considered, (18)F-FDG provided additional information in three cases (two metastatic forms, one multifocal disease with SDHD mutation) compared to (18)F-FDOPA. Our results suggest that tumour staging can be improved by combining (18)F-FDOPA and (18)F-FDG in the preoperative work-up of patients with abdominal and malignant PHEOs. (18)F-FDOPA is also an effective localization tool for neck PGLs. MIBG however, still has a role in these patients as MIBG and FDOPA images did not completely overlap.

  4. Monitoring of anti-cancer treatment with 18F-FDG and 18F-FLT PET: a comprehensive review of pre-clinical studies

    PubMed Central

    Jensen, Mette Munk; Kjaer, Andreas

    2015-01-01

    Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) and 3’-deoxy-3’-[18F]fluorothymidine(18F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can be visualized and quantified non-invasively by PET. With 18F-FDG and 18F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response. It is hypothesized that decreases in glycolysis and cell proliferation may occur in tumors that are sensitive to the applied cancer therapeutics and that tumors that are resistant to treatment will show unchanged glucose metabolism and cell proliferation. Whether 18F-FDG and/or 18F-FLT PET can be used for prediction of treatment response has been analyzed in many studies both following treatment with conventional chemotherapeutic agents but also following treatment with different targeted therapies, e.g. monoclonal antibodies and small molecules inhibitors. The results from these studies have been most variable; in some studies early changes in 18F-FDG and 18F-FLT uptake predicted later tumor regression whereas in other studies no change in tracer uptake was observed despite the treatment being effective. The present review gives an overview of pre-clinical studies that have used 18F-FDG and/or 18F-FLT PET for response monitoring of cancer therapeutics. PMID:26550536

  5. F18-FDG coincidence-PET in patients with suspected gynecological malignancy.

    PubMed

    Zor, E; Stokkel, M P; Ozalp, S; Vardareli, E; Yalçin, O Tarik; Ak, I

    2006-07-01

    To assess the role of F18-FDG imaging with a dual-head coincidence mode gamma camera (Co-PET) in identifying malignant tumors in patients with a suspicious adnexal mass depicted by conventional imaging methods. F18-FDG Co-PET was performed preoperatively in 18 women (mean age 56.38 years) with suspected malignant gynecologic tumors according to clinical and abdomino-pelvic/transvaginal ultrasound or computed tomography findings. Exploratory laparotomy was performed in all patients within the 10 days post-F18-FDG Co-PET study, and the definitive diagnosis of the adnexal masses was established by histopathological examination. Histopathological examinations of the surgically excised adnexal masses revealed eight malignant, one borderline, and nine benign neoplastic tumors. Four benign tumors had no F18-FDG uptake, while the remaining five tumors, all leiomyomas, showed mild FDG accumulation. Eight malignant tumors showed intense F18-FDG uptake. Sensitivity, specificity, PPV, and NPV of F18-FDG co-PET in differentiating benign from malign adnexal masses were 88%, 44%, 61%, and 80%, respectively. Tumor to background ratios (T/B) in benign lesions (2.04 +/- 0.27) were significantly lower than in malignant lesions (7.4 +/- 0.99). F18-FDG Co-PET is of clinical value when assessing suspicious malignant adnexal masses. False-negative F18-FDG results might arise from borderline disease. Moderate F18-FDG uptake in leiomyomas can result false-positive, but T/B ratios may be helpful in such cases.

  6. Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

    PubMed

    Sachpekidis, C; Goldschmidt, H; Kopka, K; Kopp-Schneider, A; Dimitrakopoulou-Strauss, A

    2018-04-10

    Despite the significant upgrading in recent years of the role of 18 F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18 F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18 F-FDG PET/CT. Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18 F-FDG PET/CT and 18 F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18 F-FDG PET/CT demonstrated focal, 18 F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18 F-FLT PET/CT showed focal, 18 F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18 F-FDG avid, focal, MM-indicative lesions were detected with 18 F-FDG PET/CT, while 17 18 F-FLT avid, focal, MM-indicative lesions were detected with 18 F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18 F-FDG PET/CT than for 18 F-FLT PET/CT. A common finding was a mismatch of focally increased 18 F-FDG uptake and reduced 18 F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18 F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV mean and SUV max were significantly higher for 18 F-FLT than for 18 F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in

  7. A Transmetalation Reaction Enables the Synthesis of [ 18F]5-Fluorouracil from [ 18F]Fluoride for Human PET Imaging

    DOE PAGES

    Hoover, Andrew J.; Lazari, Mark; Ren, Hong; ...

    2016-02-14

    Translation of new 18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [ 18F]fluoride of human doses of [ 18F]5-fluorouracil, a PET tracer for cancer imaging in humans. Here, the firstmore » preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [ 18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [ 18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [ 18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18F-fluorination.« less

  8. A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging

    PubMed Central

    2016-01-01

    Translation of new 18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [18F]fluoride of human doses of [18F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18F-fluorination. PMID:27087736

  9. A Transmetalation Reaction Enables the Synthesis of [18F]5-Fluorouracil from [18F]Fluoride for Human PET Imaging.

    PubMed

    Hoover, Andrew J; Lazari, Mark; Ren, Hong; Narayanam, Maruthi Kumar; Murphy, Jennifer M; van Dam, R Michael; Hooker, Jacob M; Ritter, Tobias

    2016-04-11

    Translation of new 18 F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18 F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18 F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [ 18 F]fluoride of human doses of [ 18 F]5-fluorouracil, a PET tracer for cancer imaging in humans. The first preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [ 18 F]5-fluorouracil precursor. Routine production of >10 mCi doses of [ 18 F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [ 18 F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18 F-fluorination.

  10. A Transmetalation Reaction Enables the Synthesis of [ 18F]5-Fluorouracil from [ 18F]Fluoride for Human PET Imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoover, Andrew J.; Lazari, Mark; Ren, Hong

    Translation of new 18F-fluorination reactions to produce radiotracers for human positron emission tomography (PET) imaging is rare because the chemistry must have useful scope and the process for 18F-labeled tracer production must be robust and simple to execute. The application of transition metal mediators has enabled impactful 18F-fluorination methods, but to date none of these reactions have been applied to produce a human-injectable PET tracer. In this article we present chemistry and process innovations that culminate in the first production from [ 18F]fluoride of human doses of [ 18F]5-fluorouracil, a PET tracer for cancer imaging in humans. Here, the firstmore » preparation of nickel σ-aryl complexes by transmetalation from arylboronic acids or esters was developed and enabled the synthesis of the [ 18F]5-fluorouracil precursor. Routine production of >10 mCi doses of [ 18F]5-fluorouracil was accomplished with a new instrument for azeotrope-free [ 18F]fluoride concentration in a process that leverages the tolerance of water in nickel-mediated 18F-fluorination.« less

  11. Comparison of [(11)C]Choline ([(11)C]CHO) and [(18)F]Bombesin (BAY 86-4367) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.

    PubMed

    Schwarzenböck, Sarah Marie; Schmeja, Philipp; Kurth, Jens; Souvatzoglou, Michael; Nawroth, Roman; Treiber, Uwe; Kundt, Guenther; Berndt, Sandra; Graham, Keith; Senekowitsch-Schmidtke, Reingard; Schwaiger, Markus; Ziegler, Sibylle I; Dinkelborg, Ludger; Wester, Hans-Jürgen; Krause, Bernd Joachim

    2016-06-01

    Carbon-11- and fluorine-18-labeled choline derivatives are commonly used in prostate cancer imaging in the clinical setting for staging and re-staging of prostate cancer. Due to a limited detection rate of established positron emission tomography (PET) tracers, there is a clinical need for innovative tumor-specific PET compounds addressing new imaging targets. The aim of this study was to compare the properties of [(18)F]Bombesin (BAY 86-4367) as an innovative biomarker for prostate cancer imaging targeting the gastrin-releasing peptide receptor and [(11)C]Choline ([(11)C]CHO) in a human prostate tumor mouse xenograft model by small animal PET/X-ray computed tomography (CT). We carried out a dual-tracer small animal PET/CT study comparing [(18)F]Bombesin and [(11)C]CHO. The androgen-independent human prostate tumor cell line PC-3 was implanted subcutaneously in the flanks of nu/nu NMRI mice (n = 10) (PET/CT measurements of two [(11)C]Choline mice could not be analyzed due to technical reasons). [(18)F]Bombesin and [(11)C]CHO PET/CT imaging was performed about 3-4 weeks after the implantation of PC-3 cells on two separate days. After the intravenous tail vein injection of 14 MBq [(18)F]Bombesin and 37 MBq [(11)C]CHO, respectively, a dynamic study over 60 min was acquired in list mode using an Inveon animal PET/CT scanner (Siemens Medical Solutions). The sequence of [(18)F]Bombesin and [(11)C]CHO was randomized. Image analysis was performed using summed images as well as dynamic data. To calculate static and dynamic tumor-to-muscle (T/M), tumor-to-blood (T/B), liver-to-blood (L/B), and kidney-to-blood (K/B) ratios, 4 × 4 × 4 mm(3) volumes of interest (VOIs) of tumor, muscle (thigh), liver, kidney, and blood derived from transversal slices were used. The mean T/M ratio of [(18)F]Bombesin and [(11)C]CHO was 6.54 ± 2.49 and 1.35 ± 0.30, respectively. The mean T/B ratio was 1.83 ± 0.79 for [(18)F]Bombesin and 0.55 ± 0.10 for [(11)C

  12. First experience with early dynamic (18)F-NaF-PET/CT in patients with chronic osteomyelitis.

    PubMed

    Freesmeyer, Martin; Stecker, Franz F; Schierz, Jan-Henning; Hofmann, Gunther O; Winkens, Thomas

    2014-05-01

    This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using (18)F-sodium fluoride-((18)F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed(18)F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late (18)F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late (18)F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed(18)F-NaF -PET offers additional information about early radiotracer distribution to standard (18)F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed(18)F-NaF-PET to a three-phase bone scan.

  13. Increased choline uptake in macrophages and prostate cancer cells does not allow for differentiation between benign and malignant prostate pathologies.

    PubMed

    Schwarz, Timo; Seidl, Christof; Schiemann, Matthias; Senekowitsch-Schmidtke, Reingard; Krause, Bernd Joachim

    2016-06-01

    Inflammatory cells may contribute to the choline uptake in different prostate pathologies. The aim of this study was (i) to assess if inflammatory cells incorporate choline and (ii) to potentially detect differences compared to FDG uptake. Therefore we investigated the uptake of [(3)H]choline and [(18)F]FDG in human prostate carcinoma cells and human inflammatory cells. Macrophages were cultured from isolated mononuclear cells, gained by density gradient centrifugation of human buffy coats. T-lymphocytes, B-lymphocytes and granulocytes were enriched by density gradient centrifugation before cell sorting by means of flow cytometry was performed. [(3)H]choline and [(18)F]FDG uptake of isolated inflammatory cells as well as of LNCaP and PC-3 human prostate carcinoma cells was assessed simultaneously in dual tracer uptake experiments. Macrophages showed highest [(3)H]choline and [(18)F]FDG uptake compared to the tracer uptake rates of leukocytes. [(3)H]choline uptake of macrophages was in the same range as in prostate cancer cells. Lipopolysaccharide stimulation of macrophages resulted in an increase of [(18)F]FDG uptake in macrophages, but not in an increased [(3)H]choline uptake. The high [(3)H]choline uptake in macrophages may be a source of false-positive PET results in diagnosis of prostate cancer by choline-PET/CT. As already known from FDG-PET, discrimination between tumor and inflammation in prostate cancer patients is not possible via choline-PET. The application of choline-PET for reliable primary prostate cancer detection and delineation has to be queried. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 18F-FDG PET/CT Imaging of Primary Gastric Lymphoma.

    PubMed

    Davis, Brady S; Thompson, Trevor A; Wolin, Ely A

    2016-12-01

    Primary gastric lymphoma (PGL) accounts for less than 4% of gastric neoplasms. 18 F-FDG PET with simultaneously acquired CT ( 18 F-FDG PET/CT) allows for staging and differentiation from other gastric cancers. Rapid diagnosis and staging are important because chemotherapeutic response is generally favorable. We describe a case of an 83-y-old woman with stage II 1 PGL. 18 F-FDG PET/CT can be helpful to differentiate various gastric masses and is an important factor in the staging of PGL. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  15. Expanding role of 18F-fluoro-d-deoxyglucose PET and PET/CT in spinal infections

    PubMed Central

    Rijk, Paul C.; Collins, James M. P.; Parlevliet, Thierry; Stumpe, Katrin D.; Palestro, Christopher J.

    2010-01-01

    18F-fluoro-d-deoxyglucose positron emission tomography ([18F]-FDG PET) is successfully employed as a molecular imaging technique in oncology, and has become a promising imaging modality in the field of infection. The non-invasive diagnosis of spinal infections (SI) has been a challenge for physicians for many years. Morphological imaging modalities such as conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are techniques frequently used in patients with SI. However, these methods are sometimes non-specific, and difficulties in differentiating infectious from degenerative end-plate abnormalities or postoperative changes can occur. Moreover, in contrast to CT and MRI, FDG uptake in PET is not hampered by metallic implant-associated artifacts. Conventional radionuclide imaging tests, such as bone scintigraphy, labeled leukocyte, and gallium scanning, suffer from relatively poor spatial resolution and lack sensitivity, specificity, or both. Initial data show that [18F]-FDG PET is an emerging imaging technique for diagnosing SI. [18F]-FDG PET appears to be especially helpful in those cases in which MRI cannot be performed or is non-diagnostic, and as an adjunct in patients in whom the diagnosis is inconclusive. The article reviews the currently available literature on [18F]-FDG PET and PET/CT in the diagnosis of SI. PMID:20052505

  16. (18)F-FDG and (18)F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes.

    PubMed

    Rayamajhi, Sampanna Jung; Mittal, Bhagwant Rai; Maturu, Venkata Nagarjuna; Agarwal, Ritesh; Bal, Amanjit; Dey, Pranab; Shukla, Jaya; Gupta, Dheeraj

    2016-04-01

    There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently (18)F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and (18)F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant. A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body (18)F-FLT PET/CT and (18)F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes. Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin's lymphoma and twelve patients with non-Hodgkin's lymphoma. The mean FDG SUVmax of sarcoidosis, tuberculosis, Hodgkin's and non-Hodgkin's lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUVmax was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUVmax values (p > 0.05) or FLT SUVmax values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUVmax and FLT SUVmax of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05). Though (18)F-FLT PET/CT and (18)F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism

  17. Optimization of automated large-scale production of [(18)F]fluoroethylcholine for PET prostate cancer imaging.

    PubMed

    Pascali, Giancarlo; D'Antonio, Luca; Bovone, Paola; Gerundini, Paolo; August, Thorsten

    2009-07-01

    PET tumor imaging is gaining importance in current clinical practice. FDG-PET is the most utilized approach but suffers from inflammation influences and is not utilizable in prostate cancer detection. Recently, (11)C-choline analogues have been employed successfully in this field of imaging, leading to a growing interest in the utilization of (18)F-labeled analogues: [(18)F]fluoroethylcholine (FEC) has been demonstrated to be promising, especially in prostate cancer imaging. In this work we report an automatic radiosynthesis of this tracer with high yields, short synthesis time and ease of performance, potentially utilizable in routine production sites. We used a Modular Lab system to automatically perform the two-step/one-pot synthesis. In the first step, we labeled ethyleneglycolditosylate obtaining [(18)F]fluoroethyltosylate; in the second step, we performed the coupling of the latter intermediate with neat dimethylethanolamine. The final mixture was purified by means of solid phase extraction; in particular, the product was trapped into a cation-exchange resin and eluted with isotonic saline. The optimized procedure resulted in a non decay corrected yield of 36% and produced a range of 30-45 GBq of product already in injectable form. The product was analyzed for quality control and resulted as pure and sterile; in addition, residual solvents were under the required threshold. In this work, we present an automatic FEC radiosynthesis that has been optimized for routine production. This findings should foster the interest for a wider utilization of this radiomolecule for imaging of prostate cancer with PET, a field for which no gold-standard tracer has yet been validated.

  18. 18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging.

    PubMed

    Nishii, Ryuichi; Higashi, Tatsuya; Kagawa, Shinya; Okuyama, Chio; Kishibe, Yoshihiko; Takahashi, Masaaki; Okina, Tomoko; Suzuki, Norio; Hasegawa, Hiroshi; Nagahama, Yasuhiro; Ishizu, Koichi; Oishi, Naoya; Kimura, Hiroyuki; Watanabe, Hiroyuki; Ono, Masahiro; Saji, Hideo; Yamauchi, Hiroshi

    2018-05-01

    Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2- 18 F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine ( 18 F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18 F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.1007/s12149-018-1236-1 , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18 F-FPYBF-2 in normal healthy volunteers as a first-in-man study. Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25-56) were included and underwent 18 F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan was performed six times after the injection of 18 F-FPYBF-2. After reconstructing PET and CT image data, individual organ time-activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses. Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18 F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for

  19. Prediction of standard-dose brain PET image by using MRI and low-dose brain [18F]FDG PET images.

    PubMed

    Kang, Jiayin; Gao, Yaozong; Shi, Feng; Lalush, David S; Lin, Weili; Shen, Dinggang

    2015-09-01

    Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient's exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [(18)F]FDG PET image by using a low-dose brain [(18)F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. The authors employ a regression forest for predicting the standard-dose brain [(18)F]FDG PET image by low-dose brain [(18)F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [(18)F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [(18)F]FDG PET image and substantially enhanced image quality of low

  20. Prediction of standard-dose brain PET image by using MRI and low-dose brain [18F]FDG PET images

    PubMed Central

    Kang, Jiayin; Gao, Yaozong; Shi, Feng; Lalush, David S.; Lin, Weili; Shen, Dinggang

    2015-01-01

    Purpose: Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [18F]FDG PET image by using a low-dose brain [18F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. Methods: The authors employ a regression forest for predicting the standard-dose brain [18F]FDG PET image by low-dose brain [18F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [18F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. Results: The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [18F]FDG PET image and substantially enhanced

  1. Sodium 18F-Fluoride PET/CT of Bone, Joint and Other Disorders

    PubMed Central

    Jadvar, Hossein; Desai, Bhushan; Conti, Peter S.

    2014-01-01

    The use of 18F-sodium fluoride (18F-NaF) with positron emission tomography-computed tomography (PET/CT) is increasing. This resurgence of an old tracer has been fueled by several factors including superior diagnostic performance over standard 99mTc-based bone scintigraphy, growth in the availability of PET/CT imaging systems, increase in the number of regional commercial distribution centers for PET radiotracers, the recent concerns about potential chronic shortages with 99mTc based radiotracers, and the recent decision by the Centers for Medicare and Medicaid Services to reimburse for 18F-NaF PET/CT for evaluation of patients with known or suspected bone metastases through the National Oncologic PET Registry. The major goal of this article is to review the current evidence on the diagnostic utility of 18F-NaF in the imaging assessment of bone and joint in a variety of clinical conditions. PMID:25475379

  2. Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

    DTIC Science & Technology

    2014-10-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The study investigates whether fusion PET/MRI imaging with 18F- choline PET/CT and...imaging with 18F- choline PET/CT and diffusion-weighted MRI can be successfully applied to target prostate cancer using image-guided prostate...Completed task. The 18F- choline synthesis was implemented and optimized for routine radiotracer production. RDRC committee approval as part of the IRB

  3. Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

    PubMed

    García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

    2016-01-01

    To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  4. Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-D-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy.

    PubMed

    King, Kathryn S; Chen, Clara C; Alexopoulos, Dimitrios K; Whatley, Millie A; Reynolds, James C; Patronas, Nicholas; Ling, Alexander; Adams, Karen T; Xekouki, Paraskevi; Lando, Howard; Stratakis, Constantine A; Pacak, Karel

    2011-09-01

    Accurate diagnosis of head and neck paragangliomas is often complicated by biochemical silence and lack of catecholamine-associated symptoms, making accurate anatomical and functional imaging techniques essential to the diagnostic process. Ten patients (seven SDHD, three SDHB), with a total of 26 head and neck paragangliomas, were evaluated with anatomical and functional imaging. This study compares five different functional imaging techniques [(18)F-fluorodihydroxyphenylalanine ((18)F-FDOPA) positron emission tomography (PET), (18)F-fluorodopamine ((18)F-FDA) PET/computed tomography (CT), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) PET/CT, (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy, and (111)In-pentetreotide scintigraphy] in the localization of head and neck paragangliomas. Prospectively (18)F-FDOPA PET localized 26 of 26 lesions in the 10 patients, CT/magnetic resonance imaging localized 21 of 26 lesions, (18)F-FDG PET/CT localized 20 of 26 lesions, (111)In-pentetreotide scintigraphy localized 16 of 25 lesions, (18)F-FDA PET/CT localized 12 of 26 lesions, and (123)I-MIBG scintigraphy localized eight of 26 lesions. Differences in imaging efficacy related to genetic phenotype, even in the present small sample size, included the negativity of (18)F-FDA PET/CT and (123)I-MIBG scintigraphy in patients with SDHB mutations and the accuracy of (18)F-FDG PET/CT in all patients with SDHD mutations, as compared with the accuracy of (18)F-FDG PET/CT in only one patient with an SDHB mutation. Overall, (18)F-FDOPA PET proved to be the most efficacious functional imaging modality in the localization of SDHx-related head and neck paragangliomas and may be a potential first-line functional imaging agent for the localization of these tumors.

  5. Radiation absorbed dose estimates for 18F-BPA PET.

    PubMed

    Kono, Yuzuru; Kurihara, Hiroaki; Kawamoto, Hiroshi; Yasui, Naoko; Honda, Naoki; Igaki, Hiroshi; Itami, Jun

    2017-09-01

    Background Boron neutron capture therapy (BNCT) is a molecular radiation therapy approach based on the 10 B (n, α) 7 Li nuclear reaction in cancer cells. In BNCT, delivery of 10 B in the form of 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is important. The PET tracer 4-borono-2-18F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. Purpose To determine the biodistribution and dosimetric parameters in 18F-BPA PET/CT studies. Material and Methods Human biokinetic data were obtained during clinical 18F-BPA PET studies between February and June 2015 at one institution. Nine consecutive patients were studied prospectively. The internal radiation dose was calculated on the basis of radioactivity data from blood, urine, and normal tissue of the heart, liver, spleen, kidney, and other parts of the body at each time point using OLINDA/EXM1.1 program. We compared our calculations with published 18F-FDG data. Results Adult patients (3 men, 3 women; age range, 28-68 years) had significantly smaller absorbed doses than pediatric patients (3 patients; age range, 5-12 years) ( P = 0.003). The mean effective dose was 57% lower in adult patients compared with pediatric patients. Mean effective doses for 18F-BPA were 25% lower than those for 18F-FDG presented in International Commission of Radiation Protection (ICRP) publication 106. Conclusion We found significant differences in organ absorbed doses for 18F-BPA against those for 18F-FDG presented in ICRP publication 106. Mean effective doses for 18F-BPA were smaller than those for 18F-FDG in the publication by 0.5-38% (mean difference, 25%).

  6. [18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects.

    PubMed

    Laakso, A; Bergman, J; Haaparanta, M; Vilkman, H; Solin, O; Hietala, J

    1998-03-01

    We have characterized the usage of [18F]CFT (also known as [18F]WIN 35,428) as a radioligand for in vivo studies of human dopamine transporter by PET. CFT was labeled with 18F to a high specific activity, and dynamic PET scans were conducted in healthy volunteers at various time points up to 5 h from [18F]CFT injection. The regional distribution of [18F]CFT uptake correlated well with the known distribution of dopaminergic nerve terminals in the human brain and also with that of other dopamine transporter radioligands. Striatal binding peaked at 225 min after injection and declined thereafter, demonstrating the reversible nature of the binding to the dopamine transporter. Therefore, due to the relatively long half-life of 18F (109.8 min), PET scans with [18F]CFT could easily be conducted during the binding equilibrium, allowing estimation of Bmax/Kd values (i.e., binding potential). Binding potentials for putamen and caudate measured at equilibrium were 4.79+/-0.11 and 4.50+/-0.23, respectively. We were able to also visualize midbrain dopaminergic neurons (substantia nigra) with [18F]CFT in some subjects. In conclusion, the labeling of CFT with 18F allows PET scans to be conducted at binding equilibrium, and therefore a high signal-to-noise ratio and reliable quantification of binding potential can be achieved. With a high resolution 3D PET scanner, the quantification of extrastriatal dopamine transporters should become possible.

  7. [18F-Fluorocholine PET-CT for localization of parathyroid adenomas].

    PubMed

    Kluijfhout, Wouter P; Vriens, Menno R; Borel Rinkes, Inne H M; Valk, Gerlof D; de Klerk, John M H; de Keizer, Bart

    2015-01-01

    18F-fluorocholine PET-CT is a new imaging modality for the localization of pathological parathyroid glands in patients with primary hyperparathyroidism. The PET-CT is a combination scan that uses both the physiological information from the PET and the anatomical information from the CT. Uptake of the radio-isotope 18F-fluorocholine is increased in pathological parathyroid glands. 18F-fluorocholine PET-CT helps clinicians to localize the pathological parathyroid glands where conventional modalities fail to do so. This enables surgeons to carry out targeted minimal invasive surgery. It may also prevent the patient having to undergo a more extensive exploration, with its associated risks, and alleviate the necessity of taking medications with side effects. Although the literature on this subject is still scarce, preliminary results are promising. As any hospital with a PET-CT can perform the scan, we expect that its use in patients with hyperparathyroidism will increase over the next few years.

  8. Feasibility of TCP-based dose painting by numbers applied to a prostate case with (18)F-choline PET imaging.

    PubMed

    Dirscherl, Thomas; Rickhey, Mark; Bogner, Ludwig

    2012-02-01

    A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with (18)F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1Gy to 99.3Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64Gy and a standard deviation of 4.02Gy. Film verification showed a reasonable agreement of planned and delivered dose. If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. Copyright © 2012. Published by Elsevier GmbH.

  9. Is integrated 18F-FDG PET/MRI superior to 18F-FDG PET/CT in the differentiation of incidental tracer uptake in the head and neck area?

    PubMed

    Schaarschmidt, Benedikt Michael; Gomez, Benedikt; Buchbender, Christian; Grueneisen, Johannes; Nensa, Felix; Sawicki, Lino Morris; Ruhlmann, Verena; Wetter, Axel; Antoch, Gerald; Heusch, Philipp

    2017-01-01

    We aimed to investigate the accuracy of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) compared with contrast-enhanced 18F-FDG PET/computed tomography (PET/CT) for the characterization of incidental tracer uptake in examinations of the head and neck. A retrospective analysis of 81 oncologic patients who underwent contrast-enhanced 18F-FDG PET/CT and subsequent PET/MRI was performed by two readers for incidental tracer uptake. In a consensus reading, discrepancies were resolved. Each finding was either characterized as most likely benign, most likely malignant, or indeterminate. Using all available clinical information including results from histopathologic sampling and follow-up examinations, an expert reader classified each finding as benign or malignant. McNemar's test was used to compare the performance of both imaging modalities in characterizing incidental tracer uptake. Forty-six lesions were detected by both modalities. On PET/CT, 27 lesions were classified as most likely benign, one as most likely malignant, and 18 as indeterminate; on PET/MRI, 31 lesions were classified as most likely benign, one lesion as most likely malignant, and 14 as indeterminate. Forty-three lesions were benign and one lesion was malignant according to the reference standard. In two lesions, a definite diagnosis was not possible. McNemar's test detected no differences concerning the correct classification of incidental tracer uptake between PET/CT and PET/MRI (P = 0.125). In examinations of the head and neck area, incidental tracer uptake cannot be classified more accurately by PET/MRI than by PET/CT.

  10. Imaging Bone–Cartilage Interactions in Osteoarthritis Using [18F]-NaF PET-MRI

    PubMed Central

    Pedoia, Valentina; Seo, Youngho; Yang, Jaewon; Bucknor, Matt; Franc, Benjamin L.; Majumdar, Sharmila

    2016-01-01

    Purpose: Simultaneous positron emission tomography–magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA). Procedures: In this article, bone turnover and remodeling was studied using [18F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [18F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake (Ki) and the normalized uptake (standardized uptake value) of [18F]-NaF in the bone. Morphological MR images and quantitative voxel-based T1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage. Results: Increases in cartilage T1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions. Conclusion: This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [18F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical

  11. Imaging melphalan therapy response in preclinical extramedullary myeloma with 18F-FDOPA and 18F-FDG PET.

    PubMed

    Hathi, Deep; DeLassus, Elizabeth; Achilefu, Samuel; McConathy, Jonathan; Shokeen, Monica

    2018-04-26

    Multiple myeloma (MM) is a debilitating neoplasm of terminally differentiated plasma B-cells that has resulted in over 13,000 deaths in 2017 alone. Combination therapies involving melphalan, a small molecule DNA alkylating agent, are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Here, we evaluated the use of 18 F-FDOPA, a clinically available positron emission tomography (PET) radiotracer with specificity to the L-type amino acid transporter-1 (LAT1), which also mediates melphalan uptake, for imaging melphalan therapy response in a preclinical immunocompetent model of MM. Methods: C57Bl/KaLwRij mice were implanted subcutaneously with unilateral murine 5TGM1-GFP tumors, and divided into three independent groups: untreated, treated beginning week 2, and treated beginning week 3 post tumor implantation. The untreated and week 2 therapy cohorts were imaged with preclinical magnetic resonance imaging (MRI) and dynamic 18 F-FDG and 18 F-FDOPA-PET/computed tomography (PET/CT) at week 4 on separate, contiguous days, while the week 3 therapy cohort was longitudinally imaged weekly for 2 weeks. Metabolic tumor volume, lesion avidity, maximum standard uptake value, and total uptake metrics were calculated for both tracers. Immunohistochemistry was performed on representative tissue from all groups for LAT1 and glucose transporter-1 (GLUT1) expression. Results: Melphalan therapy induced a statistically significant reduction in lesion avidity and uptake metrics for both 18 F-FDG and 18 F-FDOPA. There was no visible effect on GLUT1 expression, but LAT1 density was increased in the week 2 therapy cohort. Longitudinal imaging of the week 3 group showed variable changes in 18 F-FDG and 18 F-FDOPA uptake, with increase in 18 F-FDOPA lesion avidity in the 2nd week relative to baseline. LAT1 and GLUT1 surface density in the untreated tumor and week 3

  12. Assessing the role of 18F-FDG PET and 18F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies – A systematic review and meta-analysis

    PubMed Central

    Etchebehere, Elba C.; Hobbs, Brian P.; R.Milton, Denái; Malawi, Osama; Patel, Shreyaskumar; Benjamin, Robert S.; Macapinlac, Homer A.

    2016-01-01

    Purpose Twelve years ago a meta-analysis evaluated the diagnostic performance of 18F-FDG PET in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging however there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of 18F-FDG PET/CT and determine if there is added value when compared to PET. Patients and Methods A systematic review of English articles using MEDLINE PubMed, the Cochrane Library and EMBASE were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of 18F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included. Results Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60%) malignant tumors and 306 benign lesions. The 18F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive and negative predictive values for diagnosing MsSTL was 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94) and 0.91 (0.83, 0.99), respectively. The posterior mean (95% HPD interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy and positive predictive value when compared to a dedicated PET (0.85, 0.89 and 0.91 vs 0.71, 0.85 and 0.82, respectively). Conclusions 18F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate, specific and has a higher positive predictive value than PET. PMID:26631240

  13. Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer.

    PubMed

    Kitajima, Kazuhiro; Yamamoto, Shingo; Odawara, Soichi; Kobayashi, Kaoru; Fujiwara, Masayuki; Kamikonya, Norihiko; Fukushima, Kazuhito; Nakanishi, Yukako; Hashimoto, Takahiko; Yamada, Yusuke; Suzuki, Toru; Kanematsu, Akihiro; Nojima, Michio; Yamakado, Koichiro

    2018-06-01

    We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men.

  14. Site specific measurements of bone formation using [18F] sodium fluoride PET/CT

    PubMed Central

    Puri, Tanuj; Siddique, Musib; Frost, Michelle L.; Moore, Amelia E. B.; Fogelman, Ignac

    2018-01-01

    Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer. PMID:29541623

  15. Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

    PubMed

    Blake, Glen M; Puri, Tanuj; Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac

    2018-02-01

    Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([ 18 F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [ 18 F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [ 18 F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [ 18 F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

  16. Does Delayed-Time-Point Imaging Improve 18F-FDG-PET in Patients With MALT Lymphoma?

    PubMed Central

    Mayerhoefer, Marius E.; Giraudo, Chiara; Senn, Daniela; Hartenbach, Markus; Weber, Michael; Rausch, Ivo; Kiesewetter, Barbara; Herold, Christian J.; Hacker, Marcus; Pones, Matthias; Simonitsch-Klupp, Ingrid; Müllauer, Leonhard; Dolak, Werner; Lukas, Julius; Raderer, Markus

    2016-01-01

    Purpose To determine whether in patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue lymphoma (MALT), delayed–time-point 2-18F-fluoro-2-deoxy-d-glucose-positron emission tomography (18F-FDG-PET) performs better than standard–time-point 18F-FDG-PET. Materials and Methods Patients with untreated histologically verified MALT lymphoma, who were undergoing pretherapeutic 18F-FDG-PET/computed tomography (CT) and consecutive 18F-FDG-PET/magnetic resonance imaging (MRI), using a single 18F-FDG injection, in the course of a larger-scale prospective trial, were included. Region-based sensitivity and specificity, and patient-based sensitivity of the respective 18F-FDG-PET scans at time points 1 (45–60 minutes after tracer injection, TP1) and 2 (100–150 minutes after tracer injection, TP2), relative to the reference standard, were calculated. Lesion-to-liver and lesion-to-blood SUVmax (maximum standardized uptake values) ratios were also assessed. Results 18F-FDG-PET at TP1 was true positive in 15 o f 23 involved regions, and 18F-FDG-PET at TP2 was true-positive in 20 of 23 involved regions; no false-positive regions were noted. Accordingly, region-based sensitivities and specificities were 65.2% (confidence interval [CI], 45.73%–84.67%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP1; and 87.0% (CI, 73.26%–100%) and 100% (CI, 100%-100%) for 18F-FDG-PET at TP2, respectively. FDG-PET at TP1 detected lymphoma in at least one nodal or extranodal region in 7 of 13 patients, and 18F-FDG-PET at TP2 in 10 of 13 patients; accordingly, patient-based sensitivity was 53.8% (CI, 26.7%–80.9%) for 18F-FDG-PET at TP1, and 76.9% (CI, 54.0%–99.8%) for 18F-FDG-PET at TP2. Lesion-to-liver and lesion-to-blood maximum standardized uptake value ratios were significantly lower at TP1 (ratios, 1.05 ± 0.40 and 1.52 ± 0.62) than at TP2 (ratios, 1.67 ± 0.74 and 2.56 ± 1.10; P = 0.003 and P = 0.001). Conclusions Delayed–time-point imaging

  17. Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases.

    PubMed

    Li, Yuxin; Schiepers, Christiaan; Lake, Ralph; Dadparvar, Simin; Berenji, Gholam R

    2012-01-01

    (18)F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using (18)F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that (18)F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to (99m)Tc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for (18)F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using (18)F-fluoride in both benign and malignant bone disorders. Published by Elsevier Inc.

  18. Positron emission tomography (PET) imaging with 18F-based radiotracers

    PubMed Central

    Alauddin, Mian M

    2012-01-01

    Positron Emission Tomography (PET) is a nuclear medicine imaging technique that is widely used in early detection and treatment follow up of many diseases, including cancer. This modality requires positron-emitting isotope labeled biomolecules, which are synthesized prior to perform imaging studies. Fluorine-18 is one of the several isotopes of fluorine that is routinely used in radiolabeling of biomolecules for PET; because of its positron emitting property and favorable half-life of 109.8 min. The biologically active molecule most commonly used for PET is 2-deoxy-2-18F-fluoro-β-D-glucose (18F-FDG), an analogue of glucose, for early detection of tumors. The concentrations of tracer accumulation (PET image) demonstrate the metabolic activity of tissues in terms of regional glucose metabolism and accumulation. Other tracers are also used in PET to image the tissue concentration. In this review, information on fluorination and radiofluorination reactions, radiofluorinating agents, and radiolabeling of various compounds and their application in PET imaging is presented. PMID:23133802

  19. Prediction of standard-dose brain PET image by using MRI and low-dose brain [{sup 18}F]FDG PET images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kang, Jiayin; Gao, Yaozong; Shi, Feng

    Purpose: Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. Asmore » yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [{sup 18}F]FDG PET image by using a low-dose brain [{sup 18}F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. Methods: The authors employ a regression forest for predicting the standard-dose brain [{sup 18}F]FDG PET image by low-dose brain [{sup 18}F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [{sup 18}F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. Results: The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [{sup 18}F

  20. The Role of 18F-FDG PET/CT Integrated Imaging in Distinguishing Malignant from Benign Pleural Effusion.

    PubMed

    Sun, Yajuan; Yu, Hongjuan; Ma, Jingquan; Lu, Peiou

    2016-01-01

    The aim of our study was to evaluate the role of 18F-FDG PET/CT integrated imaging in differentiating malignant from benign pleural effusion. A total of 176 patients with pleural effusion who underwent 18F-FDG PET/CT examination to differentiate malignancy from benignancy were retrospectively researched. The images of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were visually analyzed. The suspected malignant effusion was characterized by the presence of nodular or irregular pleural thickening on CT imaging. Whereas on PET imaging, pleural 18F-FDG uptake higher than mediastinal activity was interpreted as malignant effusion. Images of 18F-FDG PET/CT integrated imaging were interpreted by combining the morphologic feature of pleura on CT imaging with the degree and form of pleural 18F-FDG uptake on PET imaging. One hundred and eight patients had malignant effusion, including 86 with pleural metastasis and 22 with pleural mesothelioma, whereas 68 patients had benign effusion. The sensitivities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging in detecting malignant effusion were 75.0%, 91.7% and 93.5%, respectively, which were 69.8%, 91.9% and 93.0% in distinguishing metastatic effusion. The sensitivity of 18F-FDG PET/CT integrated imaging in detecting malignant effusion was higher than that of CT imaging (p = 0.000). For metastatic effusion, 18F-FDG PET imaging had higher sensitivity (p = 0.000) and better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with CT imaging (Kappa = 0.917 and Kappa = 0.295, respectively). The specificities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were 94.1%, 63.2% and 92.6% in detecting benign effusion. The specificities of CT imaging and 18F-FDG PET/CT integrated imaging were higher than that of 18F-FDG PET imaging (p = 0.000 and p = 0.000, respectively), and CT imaging had better diagnostic consistency with 18F-FDG PET/CT integrated

  1. The Role of 18F-FDG PET/CT Integrated Imaging in Distinguishing Malignant from Benign Pleural Effusion

    PubMed Central

    Sun, Yajuan; Yu, Hongjuan; Ma, Jingquan

    2016-01-01

    Objective The aim of our study was to evaluate the role of 18F-FDG PET/CT integrated imaging in differentiating malignant from benign pleural effusion. Methods A total of 176 patients with pleural effusion who underwent 18F-FDG PET/CT examination to differentiate malignancy from benignancy were retrospectively researched. The images of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were visually analyzed. The suspected malignant effusion was characterized by the presence of nodular or irregular pleural thickening on CT imaging. Whereas on PET imaging, pleural 18F-FDG uptake higher than mediastinal activity was interpreted as malignant effusion. Images of 18F-FDG PET/CT integrated imaging were interpreted by combining the morphologic feature of pleura on CT imaging with the degree and form of pleural 18F-FDG uptake on PET imaging. Results One hundred and eight patients had malignant effusion, including 86 with pleural metastasis and 22 with pleural mesothelioma, whereas 68 patients had benign effusion. The sensitivities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging in detecting malignant effusion were 75.0%, 91.7% and 93.5%, respectively, which were 69.8%, 91.9% and 93.0% in distinguishing metastatic effusion. The sensitivity of 18F-FDG PET/CT integrated imaging in detecting malignant effusion was higher than that of CT imaging (p = 0.000). For metastatic effusion, 18F-FDG PET imaging had higher sensitivity (p = 0.000) and better diagnostic consistency with 18F-FDG PET/CT integrated imaging compared with CT imaging (Kappa = 0.917 and Kappa = 0.295, respectively). The specificities of CT imaging, 18F-FDG PET imaging and 18F-FDG PET/CT integrated imaging were 94.1%, 63.2% and 92.6% in detecting benign effusion. The specificities of CT imaging and 18F-FDG PET/CT integrated imaging were higher than that of 18F-FDG PET imaging (p = 0.000 and p = 0.000, respectively), and CT imaging had better diagnostic consistency with

  2. Prospective Comparison of 99mTc-MDP Scintigraphy, Combined 18F-NaF and 18F-FDG PET/CT, and Whole-Body MRI in Patients with Breast and Prostate Cancer.

    PubMed

    Minamimoto, Ryogo; Loening, Andreas; Jamali, Mehran; Barkhodari, Amir; Mosci, Camila; Jackson, Tatianie; Obara, Piotr; Taviani, Valentina; Gambhir, Sanjiv Sam; Vasanawala, Shreyas; Iagaru, Andrei

    2015-12-01

    We prospectively evaluated the use of combined (18)F-NaF/(18)F-FDG PET/CT in patients with breast and prostate cancer and compared the results with those for (99m)Tc-MDP bone scintigraphy and whole-body MRI. Thirty patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard-of-care bone scintigraphy were prospectively enrolled in this study. (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI were performed after bone scintigraphy. The whole-body MRI protocol consisted of both unenhanced and contrast-enhanced sequences. Lesions detected with each test were tabulated, and the results were compared. For extraskeletal lesions, (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI had no statistically significant differences in sensitivity (92.9% vs. 92.9%, P = 1.00), positive predictive value (81.3% vs. 86.7%, P = 0.68), or accuracy (76.5% vs. 82.4%, P = 0.56). However, (18)F-NaF/(18)F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%, P < 0.001, 89.8% vs. 74.7%, P = 0.01) and bone scintigraphy (96.2% vs. 64.6%, P < 0.001, 89.8% vs. 65.9%, P < 0.001) for the detection of skeletal lesions. Overall, (18)F-NaF/(18)F-FDG PET/CT showed higher sensitivity and accuracy than whole-body MRI (95.7% vs. 83.3%, P < 0.002, 87.6% vs. 76.0%, P < 0.02) but not statistically significantly so when compared with a combination of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P = 0.17, 87.6% vs. 83.0%, P = 0.53). (18)F-NaF/(18)F-FDG PET/CT showed no significant difference from a combination of (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI. No statistically significant differences in positive predictive value were noted among the 3 examinations. (18)F-NaF/(18)F-FDG PET/CT is superior to whole-body MRI and (99m)Tc-MDP scintigraphy for evaluation of skeletal disease extent. Further, (18)F-NaF/(18)F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. (18)F-NaF

  3. 18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals derived from a single-institution 18F-FDG-directed surgery experience: feasibility and quantification of 18F-FDG accumulation within 18F-FDG-avid lesions and background tissues

    PubMed Central

    2014-01-01

    Background 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a well-established imaging modality for a wide variety of solid malignancies. Currently, only limited data exists regarding the utility of PET/CT imaging at very extended injection-to-scan acquisition times. The current retrospective data analysis assessed the feasibility and quantification of diagnostic 18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals. Methods 18F-FDG-avid lesions (not surgically manipulated or altered during 18F-FDG-directed surgery, and visualized both on preoperative and postoperative 18F-FDG PET/CT imaging) and corresponding background tissues were assessed for 18F-FDG accumulation on same-day preoperative and postoperative 18F-FDG PET/CT imaging. Multiple patient variables and 18F-FDG-avid lesion variables were examined. Results For the 32 18F-FDG-avid lesions making up the final 18F-FDG-avid lesion data set (from among 7 patients), the mean injection-to-scan times of the preoperative and postoperative 18F-FDG PET/CT scans were 73 (±3, 70-78) and 530 (±79, 413-739) minutes, respectively (P < 0.001). The preoperative and postoperative mean 18F-FDG-avid lesion SUVmax values were 7.7 (±4.0, 3.6-19.5) and 11.3 (±6.0, 4.1-29.2), respectively (P < 0.001). The preoperative and postoperative mean background SUVmax values were 2.3 (±0.6, 1.0-3.2) and 2.1 (±0.6, 1.0-3.3), respectively (P = 0.017). The preoperative and postoperative mean lesion-to-background SUVmax ratios were 3.7 (±2.3, 1.5-9.8) and 5.8 (±3.6, 1.6-16.2), respectively, (P < 0.001). Conclusions 18F-FDG PET/CT oncologic imaging can be successfully performed at extended injection-to-scan acquisition time intervals of up to approximately 5 half-lives for 18F-FDG while maintaining good/adequate diagnostic image quality. The resultant increase in the 18F-FDG-avid lesion SUVmax values, decreased background SUVmax values, and

  4. [11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration.

    PubMed

    Sasaki, Toru

    2004-02-01

    To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.

  5. Comparison of 18F-FDG PET/CT and PET/MRI in patients with multiple myeloma

    PubMed Central

    Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Mosebach, Jennifer; Pan, Leyun; Schlemmer, Heinz-Peter; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2015-01-01

    PET/MRI represents a promising hybrid imaging modality with several potential clinical applications. Although PET/MRI seems highly attractive in the diagnostic approach of multiple myeloma (MM), its role has not yet been evaluated. The aims of this prospective study are to evaluate the feasibility of 18F-FDG PET/MRI in detection of MM lesions, and to investigate the reproducibility of bone marrow lesions detection and quantitative data of 18F-FDG uptake between the functional (PET) component of PET/CT and PET/MRI in MM patients. The study includes 30 MM patients. All patients initially underwent 18F-FDG PET/CT (60 min p.i.), followed by PET/MRI (120 min p.i.). PET/CT and PET/MRI data were assessed and compared based on qualitative (lesion detection) and quantitative (SUV) evaluation. The hybrid PET/MRI system provided good image quality in all cases without artefacts. PET/MRI identified 65 of the 69 lesions, which were detectable with PET/CT (94.2%). Quantitative PET evaluations showed the following mean values in MM lesions: SUVaverage=5.5 and SUVmax=7.9 for PET/CT; SUVaverage=3.9 and SUVmax=5.8 for PET/MRI. Both SUVaverage and SUVmax were significantly higher on PET/CT than on PET/MRI. Spearman correlation analysis demonstrated a strong correlation between both lesional SUVaverage (r=0.744) and lesional SUVmax (r=0.855) values derived from PET/CT and PET/MRI. Regarding detection of myeloma skeletal lesions, PET/MRI exhibited equivalent performance to PET/CT. In terms of tracer uptake quantitation, a significant correlation between the two techniques was demonstrated, despite the statistically significant differences in lesional SUVs between PET/CT and PET/MRI. PMID:26550538

  6. Reproducibility of 18F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR

    PubMed Central

    Fischer, B M; Aznar, M C; Hansen, A E; Vogelius, I R; Löfgren, J; Andersen, F L; Loft, A; Kjaer, A; Højgaard, L; Specht, L

    2015-01-01

    Objective: To investigate reproducibility of fluorine-18 fludeoxyglucose (18F-FDG) uptake on 18F-FDG positron emission tomography (PET)/CT and 18F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC). Methods: 30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUVmax and SUVpeak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUVmax. Bland–Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUVmax and SUVpeak were compared. The area under the curve from cumulative SUV–volume histograms were measured and tested for reproducibility of the distribution of 18F-FDG uptake. Results: 24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUVmax, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5–7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUVmax was not more reproducible than SUVpeak (p = 0.09). Conclusion: 18F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR. Advances in knowledge: This is the first report to test reproducibility of PET/CT and PET/MR. PMID:25634069

  7. Stereotactic Comparison Study of (18)F-Alfatide and (18)F-FDG PET Imaging in an LLC Tumor-Bearing C57BL/6 Mouse Model.

    PubMed

    Wei, Yu-Chun; Gao, Yongsheng; Zhang, Jianbo; Fu, Zheng; Zheng, Jinsong; Liu, Ning; Hu, Xudong; Hou, Wenhong; Yu, Jinming; Yuan, Shuanghu

    2016-06-28

    This study aimed to stereotactically compare the PET imaging performance of (18)F-Alfatide ((18)F-ALF-NOTA-PRGD2, denoted as (18)F-Alfatide) and (18)F-fluorodeoxyglucose (FDG) and immunohistochemistry (IHC) staining in Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mouse model. (18)F-FDG standard uptake values (SUVs) were higher than (18)F-Alfatide SUVs in tumors, most of the normal tissues and organs except for the bladder. Tumor-to-brain, tumor-to-lung, and tumor-to-heart ratios of (18)F-Alfatide PET were significantly higher than those of (18)F-FDG PET (P < 0.001). The spatial heterogeneity of the tumors was detected, and the tracer accumulation enhanced from the outer layer to the inner layer consistently using the two tracers. The parameters of the tumors were significantly correlated with each other between (18)F-FDG SUV and GLUT-1 (R = 0.895, P < 0.001), (18)F-Alfatide SUV and αvβ3 (R = 0.595, P = 0.019), (18)F-FDG SUV and (18)F-Alfatide SUV (R = 0.917, P < 0.001), and GLUT-1 and αvβ3 (R = 0.637, P = 0.011). Therefore, (18)F-Alfatide PET may be an effective tracer for tumor detection, spatial heterogeneity imaging and an alternative supplement to (18)F-FDG PET, particularly for patients with enhanced characteristics in the brain, chest tumors or diabetes, meriting further study.

  8. 18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging.

    PubMed

    Caresia Aroztegui, Ana Paula; García Vicente, Ana María; Alvarez Ruiz, Soledad; Delgado Bolton, Roberto Carlos; Orcajo Rincon, Javier; Garcia Garzon, Jose Ramon; de Arcocha Torres, Maria; Garcia-Velloso, Maria Jose

    2017-10-01

    Current guidelines do not systematically recommend 18F-FDG PET/CT for breast cancer staging; and the recommendations and level of evidence supporting its use in different groups of patients vary among guidelines. This review summarizes the evidence about the role of 18F-FDG PET/CT in breast cancer staging and the therapeutic and prognostic impact accumulated in the last decade. Other related aspects, such as the association of metabolic information with biology and prognosis are considered and evidence-based recommendations for the use of 18F-FDG PET/CT in breast cancer staging are offered. We systematically searched MEDLINE for articles reporting studies with at least 30 patients related to clinical questions following the Problem/Population, Intervention, Comparison, and Outcome framework. We critically reviewed the selected articles and elaborated evidence tables structuring the summarized information into methodology, results, and limitations. The level of evidence and the grades of recommendation for the use of 18F-FDG PET/CT in different contexts are summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial staging in patients with recently diagnosed breast cancer; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak recommendation in this population. In patients with locally advanced breast cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a strong recommendation in this population. In patients with recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG PET/CT is associated with tumor biology and has prognostic implications, supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended for staging all patients with early breast cancer, although evidence of improved regional and systemic staging supports its use in locally advanced

  9. Feasibility of myocardial PET imaging using a benzylguanidine analog: meta-(3-[18F]fluoropropyl)benzylguanidine ([18F]mFPBG).

    PubMed

    Woo, Sang-Keun; Moon, Byung Seok; Kim, Bom Sahn; Kim, Min Hwan; Lee, Yong Jin; Jung, Jae Ho; Lee, Kyo Chul; Seo, Youngho; Kim, Wook; Lim, Sang Moo; Lee, Byung Chul; Kim, Sang Eun

    2018-05-03

    Global and regional sympathetic activity in the heart can be evaluated using [ 123 I]meta-iodobenzylguanidine ([ 123 I]mIBG) imaging. However, [ 123 I]mIBG is associated with low image spatial resolution and sensitivity in cardiac imaging. We investigated the capability of an F-18-labeled mIBG derivative, meta-(3-[ 18 F]fluoropropyl)benzylguanidine ([ 18 F]mFPBG), for identifying ischemic and viable myocardium in a rat model of myocardial infarction. The ex vivo biodistribution and in vivo metabolic stability of [ 18 F]mFPBG were investigated in Sprague-Dawley rats. Selective cardiac adrenergic activation was confirmed via a blocking experiment involving pretreatment with desipramine (2 mg kg -1 ), followed by the administration of [ 18 F]mFPBG. Imaging properties of [ 18 F]mFPBG were compared with those of traditional cardiac imaging radiotracers ([ 123 I]mIBG and [ 99m Tc]MIBI) in a rat model of myocardial infarction. Non-invasive image-based measurements of infarct sizes were then compared with histological findings by using Bland-Altman analysis. The differences in infarct sizes determined using histological analysis and [ 18 F]mFPBG PET were -2.55 ± 4.99% (range: -12.33 to 7.22), -2.35 ± 3.32% (range: -8.87 to 4.16), and -3.15 ± 6.16% (range: -15.24 to 8.93) at 5, 20, and 40 min, respectively. Furthermore, [ 18 F]mFPBG PET was superior to traditional imaging methods in assessing the degree of ischemia in areas of myocardial infarction, as well as the actual infarct size. Compared to [ 123 I]mIBG, [ 18 F]mFPBG showed improved spatial resolution and sensitivity in a rat model of myocardial infarction. This result suggested that [ 18 F]mFPBG is a promising cardiac PET imaging agent for potential diagnostic application in PET cardiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Demons versus Level-Set motion registration for coronary 18F-sodium fluoride PET.

    PubMed

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R; Fletcher, Alison; Motwani, Manish; Thomson, Louise E; Germano, Guido; Dey, Damini; Berman, Daniel S; Newby, David E; Slomka, Piotr J

    2016-02-27

    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18 F-sodium fluoride ( 18 F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18 F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18 F-NaF PET. To this end, fifteen patients underwent 18 F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18 F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically

  11. Demons versus level-set motion registration for coronary 18F-sodium fluoride PET

    NASA Astrophysics Data System (ADS)

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R.; Fletcher, Alison; Motwani, Manish; Thomson, Louise E.; Germano, Guido; Dey, Damini; Berman, Daniel S.; Newby, David E.; Slomka, Piotr J.

    2016-03-01

    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically

  12. Combined use of (18)F-FDG and (18)F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study.

    PubMed

    Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2015-01-01

    Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose ((18)F-FDG) and of fluorine-18-fluoromisonidazole ((18)F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with (18)F-FDG and (18)F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. (18)F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased (18)F-FDG uptake. Six patients demonstrated also in total 43 (18)F-FDG avid metastases; these patients were excluded from radiotherapy. (18)F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly (18)F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for (18)F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for (18)F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. (18)F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. (18)F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the (18)F-FDG avid NSCLCs. Lack of correlation between the two tracers' kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy.

  13. Combined use of 18F-FDG and 18F-FMISO in unresectable non-small cell lung cancer patients planned for radiotherapy: a dynamic PET/CT study

    PubMed Central

    Sachpekidis, Christos; Thieke, Christian; Askoxylakis, Vasileios; Nicolay, Nils H; Huber, Peter E; Thomas, Michael; Dimitrakopoulou, Georgia; Debus, Juergen; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2015-01-01

    Aim of this study was to evaluate and compare, by means of dynamic and static PET/CT, the distribution patterns and pharmacokinetics of fluorine-18 fluorodeoxyglucose (18F-FDG) and of fluorine-18-fluoromisonidazole (18F-FMISO) in non-small cell lung cancer (NSCLC) patients scheduled for intensity modulated radiation therapy (IMRT). Thirteen patients suffering from inoperable stage III NSCLC underwent PET/CTs with 18F-FDG and 18F-FMISO for tumor metabolism and hypoxia assessment accordingly. Evaluation of PET/CT studies was based on visual analysis, semi-quantitative (SUV) calculations and absolute quantitative estimations, after application of a two-tissue compartment model and a non-compartmental approach. 18F-FDG PET/CT revealed all thirteen primary lung tumors as sites of increased 18F-FDG uptake. Six patients demonstrated also in total 43 18F-FDG avid metastases; these patients were excluded from radiotherapy. 18F-MISO PET/CT demonstrated 12/13 primary lung tumors with faint tracer uptake. Only one tumor was clearly 18F-FMISO avid, (SUVaverage = 3.4, SUVmax = 5.0). Mean values for 18F-FDG, as derived from dPET/CT data, were SUVaverage = 8.9, SUVmax = 15.1, K1 = 0.23, k2 = 0.53, k3 = 0.17, k4 = 0.02, influx = 0.05 and fractal dimension (FD) = 1.25 for the primary tumors. The respective values for 18F-FMISO were SUVaverage = 1.4, SUVmax = 2.2, K1 = 0.26, k2 = 0.56, k3 = 0.06, k4 = 0.06, influx = 0.02 and FD = 1.14. No statistically significant correlation was observed between the two tracers. 18F-FDG PET/CT changed therapy management in six patients, by excluding them from planned IMRT. 18F-FMISO PET/CT revealed absence of significant tracer uptake in the majority of the 18F-FDG avid NSCLCs. Lack of correlation between the two tracers’ kinetics indicates that they reflect different molecular mechanisms and implies the discordance between increased glycolysis and hypoxia in the malignancy. PMID:25973334

  14. Prevalence and malignancy risk of focal colorectal incidental uptake detected by (18)F-FDG-PET or PET/CT: a meta-analysis.

    PubMed

    Treglia, Giorgio; Taralli, Silvia; Salsano, Marco; Muoio, Barbara; Sadeghi, Ramin; Giovanella, Luca

    2014-06-01

    The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography ((18)F-FDG-PET or PET/CT). A comprehensive computer literature search of studies published through July 31(st) 2012 regarding FCIs detected by (18)F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. Thirty-two studies comprising 89,061 patients evaluated by (18)F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by (18)F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6-4.7%). Overall, 1,044 FCIs detected by (18)F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60-75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. FCIs are observed in a not negligible number of patients who undergo (18)F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by (18)F-FDG-PET or PET/CT.

  15. Disseminated Multi-system Sarcoidosis Mimicking Metastases on 18F-FDG PET/CT.

    PubMed

    Makis, William; Palayew, Mark; Rush, Christopher; Probst, Stephan

    2018-06-07

    A 60-year-old female with no significant medical history presented with hematuria. A computed tomography (CT) scan revealed extensive lymphadenopathy with hypodensities in the liver and spleen, and she was referred for an 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/CT (PET/CT) study to assess for malignancy of unknown primary. PET/CT revealed extensive 18 F-FDG avid lymphadenopathy as well as innumerable intensely 18 F-FDG avid lung, liver and splenic nodules, highly concerning for malignancy. A PET-guided bone marrow biopsy of the posterior superior iliac spine revealed several non-necrotizing, well-formed granulomas, consistent with sarcoidosis. The patient was managed conservatively and remained clinically well over the subsequent 9 years of follow-up.

  16. Multimodal correlation of dynamic [18F]-AV-1451 perfusion PET and neuronal hypometabolism in [18F]-FDG PET.

    PubMed

    Hammes, Jochen; Leuwer, Isabel; Bischof, Gérard N; Drzezga, Alexander; van Eimeren, Thilo

    2017-12-01

    Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury. Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls. Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar. Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

  17. Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

    PubMed

    Conteduca, V; Scarpi, E; Caroli, P; Salvi, S; Lolli, C; Burgio, S L; Menna, C; Schepisi, G; Testoni, S; Gurioli, G; Paganelli, G; Casadio, V; Matteucci, F; De Giorgi, U

    2017-11-14

    The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.

  18. A Prospective Study Comparing 99mTc-Hydroxyethylene-Diphosphonate Planar Bone Scintigraphy and Whole-Body SPECT/CT with 18F-Fluoride PET/CT and 18F-Fluoride PET/MRI for Diagnosing Bone Metastases.

    PubMed

    Löfgren, Johan; Mortensen, Jann; Rasmussen, Sine H; Madsen, Claus; Loft, Annika; Hansen, Adam E; Oturai, Peter; Jensen, Karl Erik; Mørk, Mette Louise; Reichkendler, Michala; Højgaard, Liselotte; Fischer, Barbara M

    2017-11-01

    We prospectively evaluated and compared the diagnostic performance of 99m Tc-hydroxyethylene-diphosphonate ( 99m Tc-HDP) planar bone scintigraphy (pBS), 99m Tc-HDP SPECT/CT, 18 F-NaF PET/CT, and 18 F-NaF PET/MRI for the detection of bone metastases. Methods: One hundred seventeen patients with histologically proven malignancy referred for clinical pBS were prospectively enrolled. pBS and whole-body SPECT/CT were performed followed by 18 F-NaF PET/CT within 9 d. 18 F-NaF PET/MRI was also performed in 46 patients. Results: Bone metastases were confirmed in 16 patients and excluded in 101, which was lower than expected. The number of equivocal scans was significantly higher for pBS than for SPECT/CT and PET/CT (18 vs. 5 and 6, respectively; P = 0.004 and 0.01, respectively). When equivocal readings were excluded, no statistically significant difference in sensitivity, specificity, positive predictive value, negative predictive value, or overall accuracy were found when comparing the different imaging techniques. In the per-patient analysis, equivocal scans were either assumed positive for metastases ("pessimistic analysis") or assumed negative for metastases ("optimistic analysis"). The percentages of misdiagnosed patients for the pessimistic analysis were 21%, 15%, 9%, and 7% for pBS, SPECT/CT, PET/CT, and PET/MRI, respectively. Corresponding figures for the optimistic analysis were 9%, 12%, 5%, and 7%. In those patients identified as having bone metastases according to the reference standard, SPECT/CT, 18 F-NaF PET/CT, and PET/MRI detected additional lesions compared with pBS in 31%, 63%, and 71%, respectively. Conclusion: 18 F-NaF PET/CT and whole-body SPECT/CT resulted in a significant reduction of equivocal readings compared with pBS, which implies an improved diagnostic confidence. However, the clinical benefit of using, for example, 18 F-NaF PET/CT or PET/MRI as compared with SPECT/CT and pBS in this patient population with a relatively low prevalence of bone

  19. [(18)F]Florbetaben: a review in β-amyloid PET imaging in cognitive impairment.

    PubMed

    Syed, Yahiya Y; Deeks, Emma

    2015-07-01

    Intravenous (18)F-labelled florbetaben ([(18)F]florbetaben) [Neuraceq™] is a polyethylene glycol stilbene derivative that is approved in the USA, EU and South Korea for positron emission tomography (PET) imaging of the brain. It is used to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive impairment. In vitro, [(18)F]florbetaben has high affinity and selectivity for β-amyloid. It has a short PET scan time (15-20 min). Visual assessment of regional and whole brain [(18)F]florbetaben PET images detected brain β-amyloid with high sensitivity and specificity, with good inter-reader agreement, in a phase III study in patients with various levels of cognitive function when compared with postmortem histopathological assessment. The whole brain visual assessment displayed high positive and negative predictive values, enabling amyloid pathology to be reliably detected or excluded. Quantitative PET analyses were generally consistent with the visual assessments. [(18)F]florbetaben was generally well tolerated in clinical trials. All adverse reactions in [(18)F]florbetaben recipients were mild to moderate in severity and the most common were injection-site-related (erythema, irritation and pain). There were no serious adverse reactions related to [(18)F]florbetaben. In summary, [(18)F]florbetaben is a highly accurate β-amyloid PET tracer that has the potential to support the clinical diagnosis of Alzheimer's disease and other causes of cognitive decline.

  20. Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

    PubMed

    Schaarschmidt, Benedikt Michael; Grueneisen, Johannes; Stebner, Vanessa; Klode, Joachim; Stoffels, Ingo; Umutlu, Lale; Schadendorf, Dirk; Heusch, Philipp; Antoch, Gerald; Pöppel, Thorsten Dirk

    2018-06-06

    To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true

  1. Prevalence and malignancy risk of focal colorectal incidental uptake detected by 18F-FDG-PET or PET/CT: a meta-analysis

    PubMed Central

    Treglia, Giorgio; Taralli, Silvia; Salsano, Marco; Muoio, Barbara; Sadeghi, Ramin; Giovanella, Luca

    2014-01-01

    Background The aim of the study was to meta-analyze published data about prevalence and malignancy risk of focal colorectal incidentalomas (FCIs) detected by Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (18F-FDG-PET or PET/CT). Methods A comprehensive computer literature search of studies published through July 31st 2012 regarding FCIs detected by 18F-FDG-PET or PET/CT was performed. Pooled prevalence of patients with FCIs and risk of malignant or premalignant FCIs after colonoscopy or histopathology verification were calculated. Furthermore, separate calculations for geographic areas were performed. Finally, average standardized uptake values (SUV) in malignant, premalignant and benign FCIs were reported. Results Thirty-two studies comprising 89,061 patients evaluated by 18F-FDG-PET or PET/CT were included. The pooled prevalence of FCIs detected by 18F-FDG-PET or PET/CT was 3.6% (95% confidence interval [95% CI]: 2.6–4.7%). Overall, 1,044 FCIs detected by 18F-FDG-PET or PET/CT underwent colonoscopy or histopathology evaluation. Pooled risk of malignant or premalignant lesions was 68% (95% CI: 60–75%). Risk of malignant and premalignant FCIs in Asia-Oceania was lower compared to that of Europe and America. A significant overlap in average SUV was found between malignant, premalignant and benign FCIs. Conclusions FCIs are observed in a not negligible number of patients who undergo 18F-FDG-PET or PET/CT studies with a high risk of malignant or premalignant lesions. SUV is not reliable as a tool to differentiate between malignant, premalignant and benign FCIs. Further investigation is warranted whenever FCIs are detected by 18F-FDG-PET or PET/CT. PMID:24991198

  2. Prognostic value of 18F-choline PET/CT metabolic parameters in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

    PubMed

    Caroli, Paola; De Giorgi, Ugo; Scarpi, Emanuela; Fantini, Lorenzo; Moretti, Andrea; Galassi, Riccardo; Celli, Monica; Conteduca, Vincenza; Rossi, Lorena; Bianchi, Emanuela; Paganelli, Giovanni; Matteucci, Federica

    2018-03-01

    The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. We observed a median SMTV of 130 cm 3 , median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.

  3. F-18 sodium fluoride PET/CT does not effectively image myocardial inflammation due to suspected cardiac sarcoidosis.

    PubMed

    Weinberg, Richard L; Morgenstern, Rachelle; DeLuca, Albert; Chen, Jennifer; Bokhari, Sabahat

    2017-12-01

    Sarcoidosis is an inflammatory disorder of unknown etiology that can involve the heart. While effective in imaging cardiac sarcoidosis, F-18 fluorodeoxyglucose (FDG) PET/CT often shows non-specific myocardial uptake. F-18 sodium fluoride (NaF) has been used to image inflammation in coronary artery plaques and has low background myocardial uptake. Here, we evaluated whether F-18 NaF can image myocardial inflammation due to clinically suspected cardiac sarcoidosis. We performed a single institution pilot study testing if F-18 NaF PET/CT can detect myocardial inflammation in patients with suspected cardiac sarcoidosis. Patients underwent cardiac PET/CT with F-18 FDG as part of their routine care and subsequently received an F-18 NaF PET/CT scan. Three patients underwent F-18 FDG and F-18 NaF imaging. In all patients, there was F-18 FDG uptake consistent with cardiac sarcoidosis. The F-18 NaF PET/CT scans showed no myocardial uptake. In this small preliminary study, PET/CT scan using F-18 NaF does not appear to detect myocardial inflammation caused by suspected cardiac sarcoidosis.

  4. Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy.

    PubMed

    Uprimny, Christian; Svirydenka, Anna; Fritz, Josef; Kroiss, Alexander Stephan; Nilica, Bernhard; Decristoforo, Clemens; Haubner, Roland; von Guggenberg, Elisabeth; Buxbaum, Sabine; Horninger, Wolfgang; Virgolini, Irene Johanna

    2018-05-16

    The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [ 18 F]sodium fluoride ( 18 F-NaF) PET/CT. Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68 Ga-PSMA-11 PET/CT and 18 F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18 F-NaF PET and 68 Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV max ) and compared to background activity of normal bone. In addition, SUV max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. In contrast to 468 PET-positive lesions suggestive of bone metastases on 18 F-NaF PET, only 351 of the lesions were also judged positive on 68 Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18 F-NaF PET compared to 68 Ga-PSMA-11 PET, showing a median SUV max of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68 Ga-PSMA-11 PET, with a median SUV max of 1.0 in comparison to 2.7 on 18 F-NaF PET; however, tumour to background ratio was significantly higher on 18 F-NaF PET (9.8 versus 5.9 on 68 Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18 F-NaF PET revealed median SUV max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68 Ga-PSMA-11 PET median SUV max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between 18 F-NaF PET

  5. Does Choline PET/CT Change the Management of Prostate Cancer Patients With Biochemical Failure?

    PubMed

    Goldstein, Jeffrey; Even-Sapir, Einat; Ben-Haim, Simona; Saad, Akram; Spieler, Benjamin; Davidson, Tima; Berger, Raanan; Weiss, Ilana; Appel, Sarit; Lawrence, Yaacov R; Symon, Zvi

    2017-06-01

    treatment approach in 18 of 33 (55%) patients (P=0.05). Sixteen of 27 patients (59%) treated previously with radiation were retreated with RT and delayed or eliminated androgen deprivation therapy: 1 received salvage brachytherapy, 10 received salvage pelvic lymph node or prostate fossa irradiation, 2 brachytherapy failures received salvage prostate and lymph nodes IMRT, and 3 with solitary bone metastasis were treated with radiosurgery. Eleven of 16 patients retreated responded to salvage therapy with a significant PSA response (<0.2 ng/mL), 2 patients had partial biochemical responses, and 3 patients failed. The median duration of response was 500±447 days. Two of 6 patients with no prior RT were referred for salvage prostatic fossa RT: 1 received dose escalation for disease identified in the prostate fossa and another had inclusion of "hot" pelvic lymph nodes in the treatment volume. These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

  6. Paraneoplastic syndromes: detection of malignant tumors using [(18)F]FDG-PET.

    PubMed

    Berner, U; Menzel, C; Rinne, D; Kriener, S; Hamscho, N; Döbert, N; Diehl, M; Kaufmann, R; Grünwald, F

    2003-06-01

    Paraneoplastic syndromes (PS) comprise a variety of clinical symptoms and diseases associated with underlying malignancy. Differentiation towards benign autoimmune diseases is necessary due to different therapeutic options. This diagnostic challenge includes cost- and time-consuming methods and is not successful in many cases. The aim of this study was the evaluation of [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) for detecting or ruling out malignancy in these patients. In this retrospective work-up a total of 30 patients with suspected PS (m:f = 17:13, mean age 55, range 22-76 years) were examined with [(18)F]FDG-PET between 1996 and 2001. Diagnoses were erythrodermia, cerebellar degeneration, dermatomyositis, polyneuropathia and others. PET scans were compared to histopathological (n=14), radiological and follow up data (mean follow up 3.6 years, range 1-6 years). In 7 out of 30 patients (23%) an underlying malignancy was detected. Six out of 7 malignant neoplasms showed a distinctly increased glucose consumption. One benign neoplasm caused increased tracer uptake, another PET positive patient refused biopsy and showed no growth of a malignant tumour during clinical follow up of 28 months. The remaining 21 patients without suspicious glucose consumption did not demonstrate a malignancy in other diagnostic modalities or during subsequent clinical follow-up. [(18)F]FDG-PET seems to be a useful tool in the diagnostic work-up of patients with suspected paraneoplastic syndrome.

  7. Influence of androgen deprivation therapy on choline PET/CT in recurrent prostate cancer.

    PubMed

    Dost, Rutger J; Glaudemans, Andor W J M; Breeuwsma, Anthonius J; de Jong, Igle J

    2013-07-01

    Recurrent prostate cancer is usually treated by combining radiotherapy and androgen deprivation therapy. To stage the cancer, choline positron emission tomography (PET)/CT can be performed. It is generally thought that androgen deprivation therapy does not influence choline PET/CT. In this article we focus on the molecular backgrounds of choline and androgens, and the results of preclinical and clinical studies performed using PET/CT. Using PubMed, we looked for the relevant articles about androgen deprivation therapy and choline PET/CT. During ADT, a tendency of decreased uptake of choline in prostate cancer was observed, in particular in hormone-naïve patients. We conclude that in order to prevent false-negative choline PET/CT scans androgen deprivation should be withheld prior to scanning, especially in hormone-naïve patients.

  8. 18F-FDG PET/CT in differentiating malignant from benign origins of obstructive jaundice.

    PubMed

    Wang, Shao-Bo; Wu, Hu-Bing; Wang, Quan-Shi; Zhou, Wen-Lan; Tian, Ying; Ji, Yun-Hai; Lv, Liang

    2015-10-01

    The various origins of obstructive jaundice make the diagnosis of the disease difficult. This study was undertaken to evaluate the role of 18F-FDG PET/CT in differentiating malignant from benign origins of obstructive jaundice and to quantify the added value of 18F-FDG PET/CT over conventional imaging (enhanced CT and/or MRI). Eighty-five patients with obstructive jaundice who underwent 18F-FDG PET/CT within 2 weeks after enhanced CT and/or MRI were reviewed retrospectively. All 18F-FDG PET/CT images were independently evaluated by 2 nuclear medicine physicians who were unaware of other imaging data; differences were resolved by consensus of the physicians. All conventional imaging interpretations, according to the medical records, were reviewed by 2 radiologists to determine the potential value. Final diagnoses were based on histological or surgical findings. Sixty-six patients were diagnosed with malignancies, and 19 patients with benign lesions. The maximum standardized uptake values for malignant and benign lesions causing biliary obstruction were 8.2+/-4.4 and 4.0+/-5.0, respectively (P<0.05). The sensitivity, specificity, and overall accuracy for differentiating malignant from benign origins with 18F-FDG PET/CT were 86.4% (57/66), 73.7% (14/19), and 83.5% (71/85), respectively. 18F-FDG PET/CT in conjunction with conventional imaging changed the sensitivity, specificity, and overall accuracy of conventional imaging alone from 75.8% (50/66) to 95.5% (63/66) (P<0.05), 68.4% (13/19) to 57.9% (11/19) (P>0.05), and 74.1% (63/85) to 87.1% (74/85) (P<0.05), respectively. 18F-FDG PET/CT is of great value in differentiating malignant from benign origins of obstructive jaundice and is a useful adjuvant to conventional imaging. 18F-FDG PET/CT should be recommended for further etiological clarification.

  9. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

    PubMed

    Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

    2013-12-01

    (18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P < 0.5), and that of (18)F-DOPA PET was 71.1% (McNemar, P < 0.001). The SUVmax (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for (68)Ga-DOTA-TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P < 0.0001). (68)Ga-DOTA-TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for

  10. Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer.

    PubMed

    Ueda, Shigeto; Tsuda, Hitoshi; Asakawa, Hideki; Omata, Jiro; Fukatsu, Kazuhiko; Kondo, Nobuo; Kondo, Tadaharu; Hama, Yukihiro; Tamura, Katsumi; Ishida, Jiro; Abe, Yoshiyuki; Mochizuki, Hidetaka

    2008-06-09

    Accurate evaluation of axillary lymph node (ALN) involvement is mandatory before treatment of primary breast cancer. The aim of this study is to compare preoperative diagnostic accuracy between positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) and axillary ultrasonography (AUS) for detecting ALN metastasis in patients having operable breast cancer, and to assess the clinical management of axillary 18F-FDG PET/CT for therapeutic indication of sentinel node biopsy (SNB) and preoperative systemic chemotherapy (PSC). One hundred eighty-three patients with primary operable breast cancer were recruited. All patients underwent 18F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18F-FDG PET/CT, we studied both a visual assessment of 18F-FDG uptake and standardized uptake value (SUV) for axillary staging. In a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy of ALN metastasis was 83% with 58% in sensitivity and 95% in specificity, and when cut-off point of SUV was set at 1.8, sensitivity, specificity, and accuracy were 36, 100, and 79%, respectively. On the other hand, the diagnostic accuracy of AUS was 85% with 54% in sensitivity and 99% in specificity. By the combination of 18F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18F-FDG PET uptake only, 80% (4 of 5) in AUS positive only, and 100% (28 of 28) in dual positive. By the combination of AUS and 18F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18F-FDG uptake was correlated with the maximum size and nuclear grade of metastatic foci (p = 0.006 and p = 0.03). The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation exposure by 18F

  11. Detection of bladder metabolic artifacts in (18)F-FDG PET imaging.

    PubMed

    Roman-Jimenez, Geoffrey; Crevoisier, Renaud De; Leseur, Julie; Devillers, Anne; Ospina, Juan David; Simon, Antoine; Terve, Pierre; Acosta, Oscar

    2016-04-01

    Positron emission tomography using (18)F-fluorodeoxyglucose ((18)F-FDG-PET) is a widely used imaging modality in oncology. It enables significant functional information to be included in analyses of anatomical data provided by other image modalities. Although PET offers high sensitivity in detecting suspected malignant metabolism, (18)F-FDG uptake is not tumor-specific and can also be fixed in surrounding healthy tissue, which may consequently be mistaken as cancerous. PET analyses may be particularly hampered in pelvic-located cancers by the bladder׳s physiological uptake potentially obliterating the tumor uptake. In this paper, we propose a novel method for detecting (18)F-FDG bladder artifacts based on a multi-feature double-step classification approach. Using two manually defined seeds (tumor and bladder), the method consists of a semi-automated double-step clustering strategy that simultaneously takes into consideration standard uptake values (SUV) on PET, Hounsfield values on computed tomography (CT), and the distance to the seeds. This method was performed on 52 PET/CT images from patients treated for locally advanced cervical cancer. Manual delineations of the bladder on CT images were used in order to evaluate bladder uptake detection capability. Tumor preservation was evaluated using a manual segmentation of the tumor, with a threshold of 42% of the maximal uptake within the tumor. Robustness was assessed by randomly selecting different initial seeds. The classification averages were 0.94±0.09 for sensitivity, 0.98±0.01 specificity, and 0.98±0.01 accuracy. These results suggest that this method is able to detect most (18)F-FDG bladder metabolism artifacts while preserving tumor uptake, and could thus be used as a pre-processing step for further non-parasitized PET analyses. Copyright © 2016. Published by Elsevier Ltd.

  12. [18F]FDOPA PET as an Endophenotype for Parkinson’s Disease Linkage Studies

    PubMed Central

    Racette, Brad A.; Good, Laura; Antenor, Jo Ann; McGee-Minnich, Lori; Moerlein, Stephen M.; Videen, Tom O.; Perlmutter, Joel S.

    2008-01-01

    Parkinson Disease (PD) is a late onset disorder with age-dependent penetrance that may confound genetic studies since affected individuals may not demonstrate clinical manifestations at the time of evaluation. The use of endophenotypes, biologic surrogates for clinical disease diagnoses, may permit more accurate classification of at-risk subjects. Positron emission tomography (PET) measurements of 6-[18F]fluorodopa ([18F]FDOPA) uptake indicate nigrostriatal neuronal integrity and may provide a useful endophenotype for PD linkage studies. We performed [18F]FDOPA PET in 11 members of a large, multi-incident Amish family with PD, 24 normals and 48 people with clinically definite idiopathic PD (PD controls). Clinical diagnoses in the Amish were clinically definite PD in four, clinically probable in one, clinically possible in five, and normal in one. Abnormal [18F]FDOPA posterior putamen uptake was defined as less than three standard deviations below the normal mean. The criteria were applied to the Amish sample to determine a PET endophenotype for each. We performed genetic simulations using SLINK to model the effect phenoconversion with the PET endophenotype had on logarithm of odds (LOD) scores. PET endophenotype confirmed the status of two clinically definite subjects. Two clinically definite Amish PD subjects had normal PETs. Two possible PD were converted to “PET definite PD”. The remainder had normal PETs. The average maximum LOD score with the pre-PET was 6.14±0.84. Simulating phenoconversion of subjects with unknown phenotypes increased the LOD score to 7.36±1.23. The [18F]FDOPA PET endophenotype permits phenoconversion in multi-incident PD families and may increase LOD score accuracy and power of an informative pedigree. PMID:16528749

  13. Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO).

    PubMed

    Yuan, Hong; Frank, Jonathan E; Merrill, Joseph R; Hillesheim, Daniel A; Khachaturian, Mark H; Anzellotti, Atilio I

    2016-01-01

    The hypoxia PET tracer, 1-[18F]fluoro-3-(2-nitro-1Himidazol- 1-yl)-propan-2-ol ([18F]FMISO) is the first radiotracer developed for hypoxia PET imaging and has shown promising for cancer diagnosis and prognosis. However, access to [18F]FMISO radiotracer is limited due to the needed cyclotron and radiochemistry expertise. The study aimed to develop the automated production method on the [18F]FMISO radiotracer with the novel fully automated platform of the BG75 system and validate its usage on animal tumor models. [18F]FMISO was produced with the dose synthesis cartridge automatically on the BG75 system. Validation of [18F]FMISO hypoxia imaging functionality was conducted on two tumor mouse models (FaDu/U87 tumor). The distribution of [18F]FMISO within tumor was further validated by the standard hypoxia marker EF5. The average radiochemical purity was (99±1) % and the average pH was 5.5±0.2 with other quality attributes passing standard criteria (n=12). Overall biodistribution for [18F]FMISO in both tumor models was consistent with reported studies where bladder and large intestines presented highest activity at 90 min post injection. High spatial correlation was found between [18F]FMISO autoradiography and EF5 hypoxia staining, indicating high hypoxia specificity of [18MF]FMISO. This study shows that qualified [18F]FMISO can be efficiently produced on the BG75 system in an automated "dose-on-demand" mode using single dose disposable cards. The possibilities of having a low-cost, automated system manufacturing ([18F]Fluoride production + synthesis + QC) different radiotracers will greatly enhance the potential for PET technology to reach new geographical areas and underserved patient populations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Predicting chemotherapy response to paclitaxel with 18F-Fluoropaclitaxel and PET.

    PubMed

    Hsueh, Wei-Ann; Kesner, Amanda L; Gangloff, Anne; Pegram, Mark D; Beryt, Malgorzata; Czernin, Johannes; Phelps, Michael E; Silverman, Daniel H S

    2006-12-01

    Paclitaxel is used as a chemotherapy drug for the treatment of various malignancies, including breast, ovarian, and lung cancers. To evaluate the potential of a noninvasive prognostic tool for specifically predicting the resistance of tumors to paclitaxel therapy, we examined the tumoral uptake of (18)F-fluoropaclitaxel ((18)F-FPAC) in mice bearing human breast cancer xenografts by using small-animal-dedicated PET and compared (18)F-FPAC uptake with the tumor response to paclitaxel treatment. PET data were acquired after tail vein injection of approximately 9 MBq of (18)F-FPAC in anesthetized nude mice bearing breast cancer xenografts. Tracer uptake in reconstructed images was quantified by region-of-interest analyses and compared with the tumor response, as measured by changes in tumor volume, after treatment with paclitaxel. Mice with tumors that progressed demonstrated lower tumoral uptake of (18)F-FPAC than mice with tumors that did not progress or that regressed (r = 0.55, P < 0.02; n = 19), indicating that low (18)F-FPAC uptake was a significant predictor of chemoresistance. Conversely, high (18)F-FPAC uptake predicted tumor regression. This relationship was found for mice bearing xenografts from cell lines selected to be either sensitive or intrinsically resistant to paclitaxel in vitro. PET data acquired with (18)F-FPAC suggest that this tracer holds promise for the noninvasive quantification of its distribution in vivo in a straightforward manner. In combination with approaches for examining other aspects of resistance, such quantification could prove useful in helping to predict subsequent resistance to paclitaxel chemotherapy of breast cancer.

  15. The feasibility of 18F-AlF-NOTA-PRGD2 PET/CT for monitoring early response of Endostar antiangiogenic therapy in human nasopharyngeal carcinoma xenograft model compared with 18F-FDG

    PubMed Central

    Liang, Sheng; Zhang, Caiyuan; Cheng, Weiwei; Hai, Wangxi; Yin, Bing; Wang, Dengbin

    2016-01-01

    Purpose Radiolabeled arginine-glycine-aspartic acid (RGD) peptides have been developed for PET imaging of integrin avβ3 in the tumor vasculature, leading to great potential for noninvasively evaluating tumor angiogenesis and monitoring antiangiogenic treatment. The aim of this study was to investigate a novel one-step labeled integrin-targeted tracer, 18F-AlF-NOTA-PRGD2, for PET/CT for detecting tumor angiogenesis and monitoring the early therapeutic efficacy of antiangiogenic agent Endostar in human nasopharyngeal carcinoma (NPC) xenograft model. Experimental design and results Mice bearing NPC underwent 18F-AlF-NOTA-PRGD2 PET/CT at baseline and after 2, 4, 7, and 14 days of consecutive treatment with Endostar or PBS, compared with 18F-FDG PET/CT. Tumors were harvested at all imaging time points for histopathological analysis with H & E and microvessel density (MVD) and integrin avβ3 immunostaining. The maximum percent injected dose per gram of body weight (%ID/gmax) tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT was significantly lower than that in the control group starting from day 2 (p < 0.01), much earlier and more accurately than that of 18F-FDG PET/CT. Moreover, a moderate linear correlation was observed between tumor MVD and the corresponding tumor uptake of 18F-AlF-NOTA-PRGD2 PET/CT (r = 0.853, p < 0.01). Conclusions 18F-AlF-NOTA-PRGD2 PET/CT can be used for in vivo angiogenesis imaging and monitoring early response to Endostar antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation. PMID:27029065

  16. Quantitative assessment of atherosclerotic plaques on (18)F-FDG PET/MRI: comparison with a PET/CT hybrid system.

    PubMed

    Li, Xiang; Heber, Daniel; Rausch, Ivo; Beitzke, Dietrich; Mayerhoefer, Marius E; Rasul, Sazan; Kreissl, Michael; Mitthauser, Markus; Wadsak, Wolfgang; Hartenbach, Markus; Haug, Alexander; Zhang, Xiaoli; Loewe, Christian; Beyer, Thomas; Hacker, Marcus

    2016-07-01

    PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. SUVmax and TBRmax values are widely accepted reference

  17. Defining optimal tracer activities in pediatric oncologic whole-body 18F-FDG-PET/MRI.

    PubMed

    Gatidis, Sergios; Schmidt, Holger; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schäfer, Jürgen F

    2016-12-01

    To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined 18 F-FDG-PET/MRI in pediatric oncology. 30 18 F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12 ± 5.6 [1-18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25-2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUV mean and SUV max ) as well as SUV variation (SUV var ) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal 18 F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities. Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUV mean and SUV max were below 5 % at 18 F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg 18 F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg 18 F-FDG or higher. Administration of 18 F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations. Significant reduction in administered 18 F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of 18 F-FDG or other tracers for specific clinical questions have to be further established in selected patient

  18. Biodisposition and metabolism of [18F]fluorocholine in 9L glioma cells and 9L glioma-bearing Fisher rats

    PubMed Central

    Bansal, Aditya; Shuyan, Wang; Hara, Toshiko; Harris, Robert A.; DeGrado, Timothy R.

    2008-01-01

    Purpose [18F]Fluorocholine [18F]FCH) was developed as an analog of [11C]choline for tumor imaging, however, its metabolic handling remains ill-defined. In this study, the metabolism of [18F]FCH is evaluated in cultured 9L glioma cells and Fisher 344 rats bearing 9L glioma tumors. Methods 9L glioma cells were incubated with [18F]FCH and [14C]choline under normoxic and hypoxic (1% O2) conditions and analyzed for metabolic fate. [18F]FCH and [14C]choline kinetics and metabolism were studied in Fisher 344 rats bearing subcutaneous 9L tumors. Results [18F]FCH and [14C]choline were similarly metabolized in 9L cells in both normoxic and hypoxic conditions over a 2 hr incubation period. In normoxia, radioactivity was predominantly in phosphorylated form for both tracers after 5 min incubation. In hypoxia, the tracers remained mainly in nonmetabolized form at early timepoints (< 20 min). Slow dephosphorylation of intracellular [18F]phosphofluorocholine (0.043–0.060 min−1) and [14C]phosphocholine (0.072–0.088 min−1) was evidenced via efflux measurements. In rat, both [18F]FCH and [14C]choline showed high renal and hepatic uptake. Blood clearance of both tracers was rapid with oxidative metabolites, [18F]fluorobetaine and [14C]betaine, representing the majority of radiolabel in plasma after 5 min post-injection. Oxidation (in liver) and lipid incorporation (in lung) were somewhat slower for [18F]FCH relative to [14C]choline. The majority of radiolabel in hypoxic subcutaneous tumor, as in hypoxic cultured 9L cells, was found as nonmetabolized [18F]FCH and [14C]choline. Conclusions [18F]FCH mimics choline uptake and metabolism by 9L glioma cells and tumors. However, subtle changes in biodistribution, oxidative metabolism, dephosphorylation, lipid incorporation and renal excretion show moderate effects of the presence of the radiofluorine atom in [18F]FCH. The decrease in phosphorylation of exogenous choline by cancer cells should be considered in interpretation of PET

  19. Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity

    PubMed Central

    Kråkenes, Jostein; Brauckhoff, Katrin; Haugland, Hans Kristian; Heinecke, Achim; Akslen, Lars A; Varhaug, Jan Erik; Brauckhoff, Michael

    2015-01-01

    Background Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131). Purpose To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT. Material and Methods Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard. Results Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%). Conclusion In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed. PMID:25770086

  20. F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Anna M.

    2013-01-18

    The goal of the proposed work is to develop novel dual-labeled molecular imaging probes for multimodality imaging. Based on small, engineered antibodies called diabodies, these probes will be radioactively tagged with Fluorine-18 for PET imaging, and fused to luciferases for optical (bioluminescence) detection. Performance will be evaluated and validated using a prototype integrated optical-PET imaging system, OPET. Multimodality probes for optical-PET imaging will be based on diabodies that are dually labeled with 18F for PET detection and fused to luciferases for optical imaging. 1) Two sets of fusion proteins will be built, targeting the cell surface markers CEA or HER2.more » Coelenterazine-based luciferases and variant forms will be evaluated in combination with native substrate and analogs, in order to obtain two distinct probes recognizing different targets with different spectral signatures. 2) Diabody-luciferase fusion proteins will be labeled with 18F using amine reactive [18F]-SFB produced using a novel microwave-assisted, one-pot method. 3) Sitespecific, chemoselective radiolabeling methods will be devised, to reduce the chance that radiolabeling will inactivate either the target-binding properties or the bioluminescence properties of the diabody-luciferase fusion proteins. 4) Combined optical and PET imaging of these dual modality probes will be evaluated and validated in vitro and in vivo using a prototype integrated optical-PET imaging system, OPET. Each imaging modality has its strengths and weaknesses. Development and use of dual modality probes allows optical imaging to benefit from the localization and quantitation offered by the PET mode, and enhances the PET imaging by enabling simultaneous detection of more than one probe.« less

  1. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging.

    PubMed

    Tarkin, Jason M; Joshi, Francis R; Evans, Nicholas R; Chowdhury, Mohammed M; Figg, Nichola L; Shah, Aarti V; Starks, Lakshi T; Martin-Garrido, Abel; Manavaki, Roido; Yu, Emma; Kuc, Rhoda E; Grassi, Luigi; Kreuzhuber, Roman; Kostadima, Myrto A; Frontini, Mattia; Kirkpatrick, Peter J; Coughlin, Patrick A; Gopalan, Deepa; Fryer, Tim D; Buscombe, John R; Groves, Ashley M; Ouwehand, Willem H; Bennett, Martin R; Warburton, Elizabeth A; Davenport, Anthony P; Rudd, James H F

    2017-04-11

    Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([ 18 F]FDG PET), [ 18 F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. This study tested the efficacy of gallium-68-labeled DOTATATE ( 68 Ga-DOTATATE), a somatostatin receptor subtype-2 (SST 2 )-binding PET tracer, for imaging atherosclerotic inflammation. We confirmed 68 Ga-DOTATATE binding in macrophages and excised carotid plaques. 68 Ga-DOTATATE PET imaging was compared to [ 18 F]FDG PET imaging in 42 patients with atherosclerosis. Target SSTR2 gene expression occurred exclusively in "proinflammatory" M1 macrophages, specific 68 Ga-DOTATATE ligand binding to SST 2 receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2 mRNA was highly correlated with in vivo 68 Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68 Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBR max ) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68 Ga-DOTATATE mTBR max predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [ 18 F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [ 18 F]FDG mTBR max differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [ 18 F]FDG spillover rendered coronary

  2. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

    PubMed

    Kim, Woosuk; Le, Thuc M; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T; Abt, Evan R; Capri, Joseph R; Austin, Wayne R; Van Valkenburgh, Juno S; Steele, Dalton; Gipson, Raymond M; Slavik, Roger; Cabebe, Anthony E; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S; Lee, Jason T; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F; Witte, Owen N; Donahue, Timothy R; Phelps, Michael E; Herschman, Harvey R; Herrmann, Ken; Czernin, Johannes; Radu, Caius G

    2016-04-12

    Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

  3. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

    PubMed Central

    Kim, Woosuk; Le, Thuc M.; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T.; Abt, Evan R.; Capri, Joseph R.; Austin, Wayne R.; Van Valkenburgh, Juno S.; Steele, Dalton; Gipson, Raymond M.; Slavik, Roger; Cabebe, Anthony E.; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S.; Lee, Jason T.; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F.; Witte, Owen N.; Donahue, Timothy R.; Phelps, Michael E.; Herschman, Harvey R.; Herrmann, Ken; Czernin, Johannes; Radu, Caius G.

    2016-01-01

    Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds—[18F]Clofarabine; 2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-adenine ([18F]CFA) and 2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-guanine ([18F]F-AraG)—for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring. PMID:27035974

  4. 18F-FDG PET/MRI fusion in characterizing pancreatic tumors: comparison to PET/CT.

    PubMed

    Tatsumi, Mitsuaki; Isohashi, Kayako; Onishi, Hiromitsu; Hori, Masatoshi; Kim, Tonsok; Higuchi, Ichiro; Inoue, Atsuo; Shimosegawa, Eku; Takeda, Yutaka; Hatazawa, Jun

    2011-08-01

    To demonstrate that positron emission tomography (PET)/magnetic resonance imaging (MRI) fusion was feasible in characterizing pancreatic tumors (PTs), comparing MRI and computed tomography (CT) as mapping images for fusion with PET as well as fused PET/MRI and PET/CT. We retrospectively reviewed 47 sets of (18)F-fluorodeoxyglucose ((18)F -FDG) PET/CT and MRI examinations to evaluate suspected or known pancreatic cancer. To assess the ability of mapping images for fusion with PET, CT (of PET/CT), T1- and T2-weighted (w) MR images (all non-contrast) were graded regarding the visibility of PT (5-point confidence scale). Fused PET/CT, PET/T1-w or T2-w MR images of the upper abdomen were evaluated to determine whether mapping images provided additional diagnostic information to PET alone (3-point scale). The overall quality of PET/CT or PET/MRI sets in diagnosis was also assessed (3-point scale). These PET/MRI-related scores were compared to PET/CT-related scores and the accuracy in characterizing PTs was compared. Forty-three PTs were visualized on CT or MRI, including 30 with abnormal FDG uptake and 13 without. The confidence score for the visibility of PT was significantly higher on T1-w MRI than CT. The scores for additional diagnostic information to PET and overall quality of each image set in diagnosis were significantly higher on the PET/T1-w MRI set than the PET/CT set. The diagnostic accuracy was higher on PET/T1-w or PET/T2-w MRI (93.0 and 90.7%, respectively) than PET/CT (88.4%), but statistical significance was not obtained. PET/MRI fusion, especially PET with T1-w MRI, was demonstrated to be superior to PET/CT in characterizing PTs, offering better mapping and fusion image quality.

  5. Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

    PubMed Central

    Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2017-01-01

    A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUVaverage for MM lesions was 11.9 and mean SUVmax was 23.2. Respectively, SUVaverage and SUVmax for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18F-NaF revealed the following mean values for MM lesions: K1 = 0.248 (1/min), k3 = 0.359 (1/min), influx (Ki) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K1 = 0.169 (1/min), k3 = 0.422 (1/min), influx (Ki) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUVaverage, SUVmax, K1, k3 and influx (Ki) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18F-NaF PET/CT in the diagnostic workup of MM. PMID:28913153

  6. Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

    PubMed

    Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2017-01-01

    A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

  7. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

    PubMed

    Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg; Detlefsen, Sönke; Brusgaard, Klaus; Rasmussen, Lars; Melikyan, Maria; Ekström, Klas; Globa, Evgenia; Rasmussen, Annett Helleskov; Hovendal, Claus; Christesen, Henrik Thybo

    2018-02-01

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

  8. Diagnostic and prognostic value of 18F-FDG PET/CT in recurrent germinal tumor carcinoma.

    PubMed

    Alongi, Pierpaolo; Evangelista, Laura; Caobelli, Federico; Spallino, Marianna; Gianolli, Luigi; Midiri, Massimo; Picchio, Maria

    2018-01-01

    The aim of this bicentric retrospective study was to assess the diagnostic performance, the prognostic value, the incremental prognostic value and the impact on therapeutic management of 18 F-FDG PET/CT in patients with suspected recurrent germinal cell testicular carcinoma (GCT). From the databases of two centers including 31,500 18 F-FDG PET/CT oncological studies, 114 patients affected by GCT were evaluated in a retrospective study. All 114 patients underwent 18 F-FDG PET/CT for suspected recurrent disease. Diagnostic performance of visually interpreted 18 F-FDG PET/CT and potential impact on the treatment decision were assessed using histology (17 patients), other diagnostic imaging modalities (i.e., contrast enhanced CT in 89 patients and MRI in 15) and clinical follow-up (114 patients) as reference. Progression-free survival (PFS) and overall survival (OS) rates were computed by means of Kaplan-Meier survival analysis. The progression rate (Hazard Ratio-HR) was determined using univariate Cox regression analysis by considering various clinical variables. Recurrent GCT was confirmed in 47 of 52 patients with pathological 18 F-FDG PET/CT findings, by means of histology in 18 patients and by other diagnostic imaging modalities/follow-up in 29. Sensitivity, specificity, accuracy, positive and negative likelihood ratio (LR+ and LR-, respectively), pre-test Odds-ratio and post-test Odds-ratio of 18 FDG PET/CT were 86.8%, 90.2%, 88.4%, 8.85, 0.14, 0.85, 8.85, respectively. 18 F-FDG PET/CT impacted significantly on therapeutic management in 26/114 (23%) cases (from palliative to curative in 12 patients, from "wait and watch" to new chemotherapy in six patients and the "wait-and-watch" approach in eight patients with unremarkable findings). At 2 and 5-year follow-up, PFS was significantly longer in patients with a negative than a pathological 18 F-FDG PET/CT scan (98% and 95% vs 48% and 38%, respectively; p = 0.02). An unremarkable scan was associated also with a

  9. 18F-FDG-PET/CT Angiography for the Diagnosis of Infective Endocarditis.

    PubMed

    Roque, A; Pizzi, M N; Cuéllar-Calàbria, H; Aguadé-Bruix, S

    2017-02-01

    This article reviews the current imaging role of 18 F-fluordeoxyglucose positron emission computed tomography ( 18 F-FDG-PET/CT) combined with cardiac CT angiography (CTA) in infective endocarditis and discusses the strengths and limitations of this technique. The diagnosis of infective endocarditis affecting prosthetic valves and intracardiac devices is challenging because echocardiography and, therefore, the modified Duke criteria have well-recognized limitations in this clinical scenario. The high sensitivity of 18 F-FDG-PET/CT for the detection of infection associated with the accurate definition of structural damage by gated cardiac CTA in a combined technique (PET/CTA) has provided a significant increase in diagnostic sensitivity for the detection of IE. PET/CTA has proven to be a useful diagnostic tool in patients with suspected infective endocarditis. The additional information provided by this technique improves diagnostic performance in prosthetic valve endocarditis when it is used in combination with the Duke criteria. The findings obtained in PET/CTA studies have been included as a major criterion in the recently updated diagnostic algorithm in infective endocarditis guidelines.

  10. 18F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer.

    PubMed

    Tsujikawa, Tetsuya; Rahman, Tasmiah; Yamamoto, Makoto; Yamada, Shizuka; Tsuyoshi, Hideaki; Kiyono, Yasushi; Kimura, Hirohiko; Yoshida, Yoshio; Okazawa, Hidehiko

    2017-11-01

    The aims of our study were to find the textural features on 18 F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between 18 F-FDG PET textural features in cervical cancer. Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment 18 F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed. Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer. 18 F-FDG PET textural features might reflect the

  11. Is choline PET useful for identifying intraprostatic tumour lesions? A literature review.

    PubMed

    Chan, Joachim; Syndikus, Isabel; Mahmood, Shelan; Bell, Lynn; Vinjamuri, Sobhan

    2015-09-01

    More than 80% of patients with intermediate-risk or high-risk localized prostate cancer are cured with radiation doses of 74-78 Gy, but high doses increase the risk for late bowel and bladder toxicity among long-term survivors. Dose painting, defined as dose escalation to areas in the prostate containing the tumour, rather than to the whole gland, minimizes dose to normal tissues and hence toxicity. It requires accurate identification of the location and size of these lesions, for which functional MRI is the current gold standard. Many studies have assessed the use of choline PET in staging newly diagnosed patients. This review will discuss important imaging variables affecting the accuracy of choline PET scans, how choline PET contributes to tumour identification and is used in radiotherapy planning and how PET can improve the patient pathway involving prostate radiotherapy. In summary, the available literature shows that the accuracy of choline PET improves with higher tracer doses and delayed imaging (although the optimal uptake time is unclear), and tumour identification by MRI is improved by the addition of PET imaging. We propose future research with prolonged choline uptake time and multiphase imaging, which may further improve accuracy.

  12. 18F-FNDP for PET Imaging of Soluble Epoxide Hydrolase.

    PubMed

    Horti, Andrew G; Wang, Yuchuan; Minn, Il; Lan, Xi; Wang, Jian; Koehler, Raymond C; Alkayed, Nabil J; Dannals, Robert F; Pomper, Martin G

    2016-11-01

    Soluble epoxide hydrolase (sEH) is a bifunctional enzyme located within cytosol and peroxisomes that converts epoxides to the corresponding diols and hydrolyzes phosphate monoesters. It serves to inactivate epoxyeicosatrienoic acids (EETs), which are generated in the brain to couple neuronal activity and cerebral blood flow in normal and pathologic states. Altered regulation of sEH was observed previously in various neuropathologic disorders including vascular dementia and stroke. Inhibitors of sEH are pursued as agents to mitigate neuronal damage after stroke. We developed N-(3,3-diphenylpropyl)-6- 18 F-fluoronicotinamide ( 18 F-FNDP), which proved highly specific for imaging of sEH in the mouse and nonhuman primate brain with PET. 18 F-FNDP was synthesized from the corresponding bromo precursor. sEH inhibitory activity of 18 F-FNDP was measured using an sEH inhibitor screening assay kit. Biodistribution was undertaken in CD-1 mice. Binding specificity was assayed in CD-1 and sEH knock-out mice and Papio anubis (baboon) through pretreatment with an sEH inhibitor to block sEH binding. Dynamic PET imaging with arterial blood sampling was performed in 3 baboons, with regional tracer binding quantified using distribution volume. The metabolism of 18 F-FNDP in baboons was assessed using high-performance liquid chromatography. 18 F-FNDP (inhibition binding affinity constant, 1.73 nM) was prepared in 1 step in a radiochemical yield of 14% ± 7%, specific radioactivity in the range of 888-3,774 GBq/μmol, and a radiochemical purity greater than 99% using an automatic radiosynthesis module. The time of preparation was about 75 min. In CD-1 mice, regional uptake followed the pattern of striatum > cortex > hippocampus > cerebellum, consistent with the known brain distribution of sEH, with 5.2% injected dose per gram of tissue at peak uptake. Blockade of 80%-90% was demonstrated in all brain regions. Minimal radiotracer uptake was present in sEH knock-out mice. PET baboon

  13. A Comparative Study of the Hypoxia PET Tracers [{sup 18}F]HX4, [{sup 18}F]FAZA, and [{sup 18}F]FMISO in a Preclinical Tumor Model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peeters, Sarah G.J.A., E-mail: sarah.peeters@maastrichtuniversity.nl; Zegers, Catharina M.L.; Lieuwes, Natasja G.

    Purpose: Several individual clinical and preclinical studies have shown the possibility of evaluating tumor hypoxia by using noninvasive positron emission tomography (PET). The current study compared 3 hypoxia PET tracers frequently used in the clinic, [{sup 18}F]FMISO, [{sup 18}F]FAZA, and [{sup 18}F]HX4, in a preclinical tumor model. Tracer uptake was evaluated for the optimal time point for imaging, tumor-to-blood ratios (TBR), spatial reproducibility, and sensitivity to oxygen modification. Methods and Materials: PET/computed tomography (CT) images of rhabdomyosarcoma R1-bearing WAG/Rij rats were acquired at multiple time points post injection (p.i.) with one of the hypoxia tracers. TBR values were calculated, andmore » reproducibility was investigated by voxel-to-voxel analysis, represented as correlation coefficients (R) or Dice similarity coefficient of the high-uptake volume. Tumor oxygen modifications were induced by exposure to either carbogen/nicotinamide treatment or 7% oxygen breathing. Results: TBR was stabilized and maximal at 2 hours p.i. for [{sup 18}F]FAZA (4.0 ± 0.5) and at 3 hours p.i. for [{sup 18}F]HX4 (7.2 ± 0.7), whereas [{sup 18}F]FMISO showed a constant increasing TBR (9.0 ± 0.8 at 6 hours p.i.). High spatial reproducibility was observed by voxel-to-voxel comparisons and Dice similarity coefficient calculations on the 30% highest uptake volume for both [{sup 18}F]FMISO (R = 0.86; Dice coefficient = 0.76) and [{sup 18}F]HX4 (R = 0.76; Dice coefficient = 0.70), whereas [{sup 18}F]FAZA was less reproducible (R = 0.52; Dice coefficient = 0.49). Modifying the hypoxic fraction resulted in enhanced mean standardized uptake values for both [{sup 18}F]HX4 and [{sup 18}F]FAZA upon 7% oxygen breathing. Only [{sup 18}F]FMISO uptake was found to be reversible upon exposure to nicotinamide and carbogen. Conclusions: This study indicates that each tracer has its own strengths and, depending on the question to be answered, a different tracer can be

  14. PET/CT with (18)F-choline after radical prostatectomy in patients with PSA ≤2 ng/ml. Can PSA velocity and PSA doubling time help in patient selection?

    PubMed

    Chiaravalloti, Agostino; Di Biagio, Daniele; Tavolozza, Mario; Calabria, Ferdinando; Schillaci, Orazio

    2016-07-01

    To investigate the performance of (18)F-fluorocholine ((18)F-FCH) PET/CT in relation to the prostate-specific antigen (PSA) kinetic indexes, PSA doubling time (PSAdt) and PSA velocity (PSAve), in detecting recurrent prostate cancer (PC) in a selected population of patients treated with radical prostatectomy and with PSA ≤2 ng/ml. The study group comprised 79 patients (mean age 70 ± 7 years, range 58 - 77 years) who had been treated with radical surgery 30 to 90 months previously and with biochemical failure (defined as a measurable serum PSA level) who were evaluated with (18)F-FCH PET/CT. In order to establish the optimal threshold for PSAdt and PSAve, the diagnostic performance of PSA, PSAdt and PSAve were compared by receiver operating characteristic analysis. In the population examined, PSA (mean ± SD) was 1.37 ± 0.44 ng/ml (range 0.21 - 2 ng/ml) before PET/CT examination, PSAdt was 10.04 ± 16.67 months and PSAve was 2.75 ± 3.11 ng/ml per year. (18)F-FCH PET/CT was positive in 44 patients (55 %). PSAve and PSAdt were significantly different between patients with a positive and a negative (18)F-FCH PET/CT scan. Thresholds of 6 months for PSAdt and 1 ng/ml per year for PSAve were selected. For PSAdt ≤6 months the detection rate (DR) was 65 %, and for PSAve >1 ng/ml per year the DR was 67 %. PSA values were not significantly different between patients with a positive and a negative PET/CT scan. The results of our study suggest that (18)F-FCH PET/CT could be considered for the evaluation of patients with biochemical recurrence of PC and with low PSA levels. Fast PSA kinetics could be useful in the selection of these patients.

  15. In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: 18F-MNI-659 and 18F-MNI-654.

    PubMed

    Barret, Olivier; Thomae, David; Tavares, Adriana; Alagille, David; Papin, Caroline; Waterhouse, Rikki; McCarthy, Timothy; Jennings, Danna; Marek, Ken; Russell, David; Seibyl, John; Tamagnan, Gilles

    2014-08-01

    Phosphodiesterase (PDE) 10A is an enzyme involved in the regulation of cyclic adenosine monophosphate and cyclic guanosine monophosphate and is highly expressed in medium-sized spiny neurons of the striatum, making it an attractive target for novel therapies for a variety of neurologic and psychiatric disorders that involve striatal function. Potential ligands for PET imaging of PDE10A have been reported. Here, we report the first-in-human characterization of 2 new PDE10A radioligands, 2-(2-(3-(1-(2-fluoroethyl)-1H-indazol-6-yl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-654) and 2-(2-(3-(4-(2-fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ((18)F-MNI-659), with the goal of selecting the best one for use in future studies interrogating pathophysiologic changes in neuropsychiatric disorders and aiding pharmaceutical development targeting PDE10A. Eleven healthy volunteers participated in this study ((18)F-MNI-654 test-retest, 2 men; (18)F-MNI-659 test-retest, 4 men and 1 woman; (18)F-MNI-659 dosimetry, 2 men and 2 women). Brain PET images were acquired over 5.5 h for (18)F-MNI-654 and over 3.5 h for (18)F-MNI-659, and pharmacokinetic modeling with plasma- and reference-region (cerebellar cortex)-based methods was performed. Whole-body PET images were acquired over 6 h for (18)F-MNI-659 and radiation dosimetry estimated with OLINDA. Both radiotracers were similarly metabolized, with about 20% of intact parent remaining at 120 min after injection. PET time-activity data demonstrated that (18)F-MNI-654 kinetics were much slower than (18)F-MNI-659 kinetics. For (18)F-MNI-659, there was good agreement between the Logan and simplified reference tissue models for nondisplaceable binding potential (BPND), supporting noninvasive quantification, with test-retest variability less than 10% and intraclass correlation greater than 0.9. The (18)F-MNI-659 effective dose was

  16. Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [18F]FDG PET.

    PubMed

    Sun, Hongzan; Xin, Jun; Zhou, Jinyuan; Lu, Zaiming; Guo, Qiyong

    2018-06-01

    The purpose of this study is to evaluate the diagnostic concordance and metric correlations of amide proton transfer (APT) imaging with gadolinium-enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[ 18 F-]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI. Twenty-one subjects underwent brain gadolinium-enhanced [ 18 F]FDG PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic criteria. Among tumors, the McNemar test was further used for concordance assessment between gadolinium-enhanced imaging, APT imaging, and [ 18 F]FDG PET. As well, the relation of metrics between APT imaging and PET was analyzed by the Pearson correlation analysis. APT imaging and gadolinium-enhanced MRI showed superior and similar diagnostic accuracy. APTW signal intensity and gadolinium enhancement were concordant in 19 tumors (100 %), while high [ 18 F]FDG avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET, there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no correlation for the remaining six [ 18 F]FDG-avid tumors. APT imaging can be used to increase diagnostic accuracy with no need to administer gadolinium chelates. APT imaging may provide an added value to [ 18 F]FDG PET in the evaluation of tumor metabolic activity during brain PET/MR studies.

  17. Biocompatible inorganic nanoparticles for [18F]-fluoride binding with applications in PET imaging

    PubMed Central

    Jauregui-Osoro, Maite; Williamson, Peter A.; Glaria, Arnaud; Sunassee, Kavitha; Charoenphun, Putthiporn; Green, Mark A.; Mullen, Gregory E. D.; Blower, Philip J.

    2014-01-01

    A wide selection of insoluble nanoparticulate metal salts was screened for avid binding of [18F]-fluoride. Hydroxyapatite and aluminium hydroxide nanoparticles showed particularly avid and stable binding of [18F]-fluoride in various biological media. The in vivo behaviour of the [18F]-labelled hydroxyapatite and aluminium hydroxide particles was determined by PET-CT imaging in mice. [18F]-labelled hydroxyapatite was stable in circulation and when trapped in various tissues (lung embolisation, subcutaneous and intramuscular), but accumulation in liver via reticuloendothelial clearance was followed by gradual degradation and release of [18F]-fluoride (over a period of 4 h) which accumulated in bone. [18F]-labelled aluminium hydroxide was also cleared to liver and spleen but degraded slightly even without liver uptake (subcutanenous and intramuscular). Both materials have properties that are an attractive basis for the design of molecular targeted PET imaging agents labelled with 18F. PMID:21394352

  18. 18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma.

    PubMed

    Wang, Hsin-Yi; Jeng, Long-Bin; Lin, Ming-Chia; Chao, Chih-Hao; Lin, Wan-Yu; Kao, Chia-Hung

    2013-01-01

    We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). Among the 127 male HCC patients who underwent 18F-FDG PET/CT scan, the 18FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. Gynecomastia is a possible cause of false-positive uptake on 18F-FDG PET/CT images. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Diagnosing neuroleukemiosis: Is there a role for 18F-FDG-PET/CT?

    PubMed

    Sabaté-Llobera, A; Cortés-Romera, M; Gamundí-Grimalt, E; Sánchez-Fernández, J J; Rodríguez-Bel, L; Gámez-Cenzano, C

    An imaging case is presented on a patient referred to our department for an 18 F-FDG-PET/CT, as a paraneoplastic syndrome was suspected due to his clinical situation. He had a history of acute myeloid leukemia (AML) treated two years earlier, with sustained complete remission to date. 18 F-FDG-PET/CT findings revealed hypermetabolism in almost all nerve roots, suggesting meningeal spread, consistent with the subsequent MRI findings. Cerebrospinal fluid (CSF) findings confirmed a leptomeningeal reactivation of AML. Although not many studies have evaluated the role of 18 F-FDG-PET/CT in leukemia, it is a noninvasive tool for detecting extramedullary sites of disease and a good imaging alternative for those patients on whom an MRI cannot be performed. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  20. Comparison of 18F SPECT with PET in myocardial imaging: a realistic thorax-cardiac phantom study.

    PubMed

    Knešaurek, Karin; Machac, Josef

    2006-10-31

    Positron emission tomography (PET) imaging with fluorine-18 (18F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 (82Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive 18F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to 18F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging. A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of 18F and 22.2 MBq of Technetium-99m (99mTc) in the SPECT study and with 7.4 MBq of 18F and 370 MBq of 82Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images. The contrast for 3 cm, 2 cm and 1 cm inserts were for 18F PET data, 1.0 +/- 0.01, 0.67 +/- 0.02 and 0.25 +/- 0.01, respectively. For 82Rb PET data, the corresponding contrast values were 0.61 +/- 0.02, 0.37 +/- 0.02 and 0.19 +/- 0.01, respectively. For 18F SPECT the contrast values were, 0.31 +/- 0.03 and 0.20 +/- 0.05 for 3 cm and 2 cm inserts, respectively. For 99mTc SPECT the contrast values were, 0.63 +/- 0.04 and 0.24 +/- 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable". For smaller defects the 99mTc/18F SPECT imaging cannot entirely replace the more expensive 82Rb/18F PET for myocardial perfusion/viability imaging, due to poorer image

  1. SU-F-I-57: Evaluate and Optimize PET Acquisition Overlap in 18F-FDG Oncology Wholebody PET/CT: Can We Scan PET Faster?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, J; Natwa, M; Hall, NC

    Purpose: The longer patient has to remain on the table during PET imaging, the higher the likelihood of motion artifacts due to patient discomfort. This study was to investigate and optimize PET acquisition overlap in 18F-FDG oncology wholebody PET/CT to speed up PET acquisition and improve patient comfort. Methods: Wholebody 18F-FDG PET/CT of phantoms, 8 pre-clinical patients (beagles) and 5 clinical oncology patients were performed in 90s/bed on a time-of-flight Gemini TF 64 system. Imaging of phantoms and beagles was acquired with reduced PET overlaps (40%, 33%, 27%, 20%, 13% and no overlap) in addition to the system default (53%).more » In human studies, 1 or 2 reduced overlaps from the listed options were used to acquire PET/CT sweeps right after the default standard of care imaging. Image quality was blindly reviewed using visual scoring criteria and quantitative SUV assessment. NEMA PET sensitivity was performed under different overlaps. Results: All PET exams demonstrated no significant impact on the visual grades for overlaps >20%. Blinded reviews assigned the best visual scores to PET using overlaps 53%–27%. Reducing overlap to 27% for oncology patients (12-bed) saved an average of ∼40% acquisition time (11min) compared to using the default overlap (18min). No significant SUV variances were found when reducing overlap to half of default for cerebellum, lung, heart, aorta, liver, fat, muscle, bone marrow, thighs and target lesions (p>0.05), except expected variability in urinary system. Conclusion: This study demonstrated by combined phantom, pre-clinical and clinical PET/CT scans that PET acquisition overlap in axial of today’s systems can be reduced and optimized. It showed that a reduction of PET acquisition overlap to 27% (half of system default) can be implemented to reduce table time by ∼40% to improve patient comfort and minimize potential motion artifacts, without prominently degrading image quality or compromising PET quantification.« less

  2. Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.

    PubMed

    Staley, J K; Van Dyck, C H; Tan, P Z; Al Tikriti, M; Ramsby, Q; Klump, H; Ng, C; Garg, P; Soufer, R; Baldwin, R M; Innis, R B

    2001-04-01

    The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.

  3. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis.

    PubMed

    Gormsen, Lars C; Haraldsen, Ate; Kramer, Stine; Dias, Andre H; Kim, Won Yong; Borghammer, Per

    2016-12-01

    Cardiac sarcoidosis (CS) is a potentially fatal condition lacking a single test with acceptable diagnostic accuracy. (18)F-FDG PET/CT has emerged as a promising imaging modality, but is challenged by physiological myocardial glucose uptake. An alternative tracer, (68)Ga-DOTANOC, binds to somatostatin receptors on inflammatory cells in sarcoid granulomas. We therefore aimed to conduct a proof-of-concept study using (68)Ga-DOTANOC to diagnose CS. In addition, we compared diagnostic accuracy and inter-observer variability of (68)Ga-DOTANOC vs. (18)F-FDG PET/CT. Nineteen patients (seven female) with suspected CS were prospectively recruited and dual tracer scanned within 7 days. PET images were reviewed by four expert readers for signs of CS and compared to the reference standard (Japanese ministry of Health and Welfare CS criteria). CS was diagnosed in 3/19 patients. By consensus, 11/19 (18)F-FDG scans and 0/19 (68)Ga-DOTANOC scans were rated as inconclusive. The sensitivity of (18)F-FDG PET for diagnosing CS was 33 %, specificity was 88 %, PPV was 33 %, NPV was 88 %, and diagnostic accuracy was 79 %. For (68)Ga-DOTANOC, accuracy was 100 %. Inter-observer agreement was poor for (18)F-FDG PET (Fleiss' combined kappa 0.27, NS) and significantly better for (68)Ga-DOTANOC (Fleiss' combined kappa 0.46, p = 0.001). Despite prolonged pre-scan fasting, a large proportion of (18)F-FDG PET/CT images were rated as inconclusive, resulting in low agreement among reviewers and correspondingly poor diagnostic accuracy. By contrast, (68)Ga-DOTANOC PET/CT had excellent diagnostic accuracy with the caveat that inter-observer variability was still significant. Nevertheless, (68)Ga-DOTANOC PET/CT looks very promising as an alternative CS PET tracer. Current Controlled Trials NCT01729169 .

  4. 18F-FDG PET/CT delayed images with forced diuresis for revaluating abdominopelvic malignancies.

    PubMed

    Wang, Hui-Chun; Wang, Zhi-Min; Wang, Yu-Bin; Chen, Xiao-Hong; Cui, Lan-Lan

    2017-05-01

    The aim of this retrospective study was to evaluate the role of delayed images after forced diuresis coupled with oral hydration in abdominopelvic 18 F-FDG PET/CT. Forty-six patients consisting of 17 urological diseases, 9 gynecological tumors, 18 colorectal malignancies, and 2 cancers of unknown primary site were retrospectively analyzed. All patients who presented with indeterminate or equivocal abdominopelvic foci on standard 18 F-FDG PET/CT underwent a delayed abdominopelvic imaging after administration of 20 mg furosemide intravenously and extra water intake of 500 mL. PET/CT images before and after furosemide were compared with each other and their findings correlated with pathology or clinical follow-up (>6 months). On initial PET/CT, the glucose metabolism characters of lesions were disguised by radioactive urine, or some undetermined 18 F-FDG accumulating foci near the urinary tract appeared. While postdiuretic PET/CT demonstrated an excellent urinary tracer washout, and hypermetabolic lesions could be clearly detected and precisely localized in all cases. On the other hand, the suspected active foci caused by potential stagnation of excreted 18 F-FDG in urinary tract were eliminated. The sensitivity, specificity, and accuracy were 94.4% (34/36), 8/10, 91.3% (42/46), respectively. Furthermore, the additional lesions with surrounding invasion or locoregional metastasis were discovered in 8 of 46 (17.4%) patients only by the delayed images, including 2 gynecological and 6 rectal malignancies. Detection of abdominopelvic malignancies can be improved using delayed 18 F-FDG PET/CT images after a diuretic and oral hydration.

  5. Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

    PubMed

    Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

    2018-05-01

    Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  6. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    PubMed Central

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  7. Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid.

    PubMed

    Lococo, Filippo; Perotti, Germano; Cardillo, Giuseppe; De Waure, Chiara; Filice, Angelina; Graziano, Paolo; Rossi, Giulio; Sgarbi, Giorgio; Stefanelli, Antonella; Giordano, Alessandro; Granone, Pierluigi; Rindi, Guido; Versari, Annibale; Rufini, Vittoria

    2015-03-01

    The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUV max, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga-DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio). Histology was used as reference standard. Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P < 0.001), whereas 18F-FDG PET/CT was superior in detecting atypical carcinoid (100% DR; P = 0.04). The SUV max ratio was the most accurate semiquantitative index in identifying TC. Overall diagnostic performance of PET/CT in detecting PC is optimal when integrating 18F-FDG and 68Ga-DOTA-peptide PET/CT findings. In the subgroup analysis, the SUV max ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

  8. Development of [18F]afatinib as new TKI-PET tracer for EGFR positive tumors.

    PubMed

    Slobbe, Paul; Windhorst, Albert D; Stigter-van Walsum, Marijke; Schuit, Robert C; Smit, Egbert F; Niessen, Heiko G; Solca, Flavio; Stehle, Gerd; van Dongen, Guus A M S; Poot, Alex J

    2014-10-01

    Afatinib is an irreversible ErbB family blocker that was approved for the treatment of EGFR mutated non-small cell lung cancer in 2013. Positron emission tomography (PET) with fluorine-18 labeled afatinib provides a means to obtain improved understanding of afatinib tumor disposition in vivo. PET imaging with [(18)F]afatinib may also provide a method to select treatment responsive patients. The aim of this study was to label afatinib with fluorine-18 and evaluate its potential as TKI-PET tracer in tumor bearing mice. A radiochemically novel coupling, using peptide coupling reagent BOP, was explored and optimized to synthesize [(18)F]afatinib, followed by a metabolite analysis and biodistribution studies in two clinically relevant lung cancer cell lines, xenografted in nude mice. A reliable [(18)F]afatinib radiosynthesis was developed and the tracer could be produced in yields of 17.0 ± 2.5% calculated from [(18)F]F(-) and >98% purity. The identity of the product was confirmed by co-injection on HPLC with non-labeled afatinib. Metabolite analysis revealed a moderate rate of metabolism, with >80% intact tracer in plasma at 45 min p.i. Biodistribution studies revealed rapid tumor accumulation and good retention for a period of at least 2 hours, while background tissues showed rapid clearance of the tracer. We have developed a method to synthesize [(18)F]afatinib and related fluorine-18 labeled 4-anilinoquinazolines. [(18)F]Afatinib showed good stability in vivo, justifying further evaluation as a TKI-PET tracer. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Synthesis and preclinical characterization of [18F]FPBZA: a novel PET probe for melanoma.

    PubMed

    Wu, Shih-Yen; Huang, Shih-Pin; Lo, Yen-Chen; Liu, Ren-Shyan; Wang, Shyh-Jen; Lin, Wuu-Jyh; Shen, Chih-Chieh; Wang, Hsin-Ell

    2014-01-01

    Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. [18F]FPBZA can be prepared efficiently with a yield of 40-50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81±0.82%ID/g), compared with A375 tumor and inflammation lesion (3.00±0.71 and 1.67±0.56%ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77±0.36%ID/g at 2 h (versus 1.16±0.23%ID/g in normal mice). Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions.

  10. Multicenter Reproducibility of 18F-Fluciclatide PET Imaging in Subjects with Solid Tumors.

    PubMed

    Sharma, Rohini; Kallur, Kumar G; Ryu, Jin S; Parameswaran, Ramanathapuram V; Lindman, Henrik; Avril, Norbert; Gleeson, Fergus V; Lee, Jong D; Lee, Kyung-Han; O'Doherty, Michael J; Groves, Ashley M; Miller, Matthew P; Somer, Edward J; Coombes, Charles R; Aboagye, Eric O

    2015-12-01

    Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for αvβ3/αvβ5 integrin, which can be radiolabeled for PET imaging of angiogenesis. Thus, (18)F-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of (18)F-fluciclatide in multiple solid-tumor types. Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of (18)F-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. (18)F-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P < 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 ± 0.18 at 40 min, 0.003 ± 0.19 at 65 min, and 0.025 ± 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter (18)F-FDG studies. The test-retest reproducibility of (18)F-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  11. Prognostic Value of [18F]-Fluoromethylcholine Positron Emission Tomography/Computed Tomography Before Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer.

    PubMed

    Cysouw, Matthijs; Bouman-Wammes, Esther; Hoekstra, Otto; van den Eertwegh, Alfons; Piet, Maartje; van Moorselaar, Jeroen; Boellaard, Ronald; Dahele, Max; Oprea-Lager, Daniela

    2018-06-01

    To investigate the predictive value of [ 18 F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT). In [ 18 F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUV mean , SUV max , SUV peak ), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm. Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013). The number of choline-avid metastases was a significant prognostic factor for progression after [ 18 F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [ 18 F]-fluoromethylcholine uptake was not prognostic for progression. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Dynamic 18F-FET PET in newly diagnosed astrocytic low-grade glioma identifies high-risk patients.

    PubMed

    Jansen, Nathalie L; Suchorska, Bogdana; Wenter, Vera; Eigenbrod, Sabina; Schmid-Tannwald, Christine; Zwergal, Andreas; Niyazi, Maximilian; Drexler, Mark; Bartenstein, Peter; Schnell, Oliver; Tonn, Jörg-Christian; Thon, Niklas; Kreth, Friedrich-Wilhelm; la Fougère, Christian

    2014-02-01

    Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P < 0.001). Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

  13. (18)F-Fluorodeoxyglucose PET/MR Imaging in Head and Neck Cancer.

    PubMed

    Platzek, Ivan

    2016-10-01

    (18)F-fluorodeoxyglucose (FDG) PET/MR imaging does not offer significant additional information in initial staging of squamous cell carcinoma of the head and neck when compared with standalone MR imaging. In patients with suspected tumor recurrence, FDG PET/MR imaging has higher sensitivity than MR imaging, although its accuracy is equivalent to the accuracy of FDG PET/CT. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Characterization of 'cold' vertebrae on 18F-FDG PET/CT.

    PubMed

    Jaimini, Abhinav; D'Souza, Maria M; Seniaray, Nikhil; Sharma, Harshul; Arbind, Arpana; Sharma, Rajnish; Mondal, Anupam

    2016-01-01

    A photon-deficient ('cold') vertebra on fluorine-18 fluorodeoxyglucose (F-FDG) PET is a known entity and can arise as a result of varying etiologies. A proper interpretation of this observation is required to make an accurate diagnosis for appropriate management. Twelve cases with 'cold' vertebrae on F-FDG PET/computed tomography (CT) were selected and analyzed from a population of 600 patients with a known malignancy who had undergone whole-body F-FDG PET/CT for staging, disease viability assessment, response to treatment, or suspected recurrence purposes. The patterns were studied and correlated with clinical history and the results of the low-dose CT performed with the PET scan for attenuation correction and anatomical localization. The most common cause for cold vertebrae was found to be postexternal radiotherapy, causing photopenia involving multiple vertebrae corresponding to the radiotherapy portals. Two other causes found in the study were the destruction of the vertebral marrow cavity by metastatic tumor cells and vertebral hemangioma. Characteristic features of 'cold' vertebrae have been described in the study with illustrations. Pattern recognition coupled with clinical history and CT correlation of 'cold' vertebrae on F-FDG PET/CT can help in diagnosing the correct underlying etiology, which can help in better management of the patients.

  15. Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques.

    PubMed

    Wang, Ji-Quan; Zheng, Qi-Huang; Fei, Xiangshu; Mock, Bruce H; Hutchins, Gary D

    2003-11-17

    Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) and 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [(18)F]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield.

  16. The diagnostic value of 18F-FDG-PET/CT and MRI in suspected vertebral osteomyelitis - a prospective study.

    PubMed

    Kouijzer, Ilse J E; Scheper, Henk; de Rooy, Jacky W J; Bloem, Johan L; Janssen, Marcel J R; van den Hoven, Leon; Hosman, Allard J F; Visser, Leo G; Oyen, Wim J G; Bleeker-Rovers, Chantal P; de Geus-Oei, Lioe-Fee

    2018-05-01

    The aim of this study was to determine the diagnostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) in diagnosing vertebral osteomyelitis. From November 2015 until December 2016, 32 patients with suspected vertebral osteomyelitis were prospectively included. All patients underwent both 18 F-FDG-PET/CT and MRI within 48 h. All images were independently reevaluated by two radiologists and two nuclear medicine physicians who were blinded to each others' image interpretation. 18 F-FDG-PET/CT and MRI were compared to the clinical diagnosis according to international guidelines. For 18 F-FDG-PET/CT, sensitivity, specificity, PPV, and NPV in diagnosing vertebral osteomyelitis were 100%, 83.3%, 90.9%, and 100%, respectively. For MRI, sensitivity, specificity, PPV, and NPV were 100%, 91.7%, 95.2%, and 100%, respectively. MRI detected more epidural/spinal abscesses. An important advantage of 18 F-FDG-PET/CT is the detection of metastatic infection (16 patients, 50.0%). 18 F-FDG-PET/CT and MRI are both necessary techniques in diagnosing vertebral osteomyelitis. An important advantage of 18 F-FDG-PET/CT is the visualization of metastatic infection, especially in patients with bacteremia. MRI is more sensitive in detection of small epidural abscesses.

  17. Synthesis and Preclinical Characterization of [18F]FPBZA: A Novel PET Probe for Melanoma

    PubMed Central

    Huang, Shih-Pin; Lo, Yen-Chen; Liu, Ren-Shyan; Shen, Chih-Chieh

    2014-01-01

    Introduction. Benzamide can specifically bind to melanoma cells. A 18F-labeled benzamide derivative, [18F]N-(2-diethylaminoethyl)-4-[2-(2-(2-fluoroethoxy) ethoxy)ethoxy]benzamide ([18F]FPBZA), was developed as a promising PET probe for primary and metastatic melanoma. Methods. [18F]FPBZA was synthesized via a one-step radiofluorination in this study. The specific uptake of [18F]FPBZA was studied in B16F0 melanoma cells, A375 amelanotic melanoma cells, and NB-DNJ-pretreated B16F0 melanoma cells. The biological characterization of [18F]FPBZA was performed on mice bearing B16F0 melanoma, A375 amelanotic melanoma, or inflammation lesion. Results. [18F]FPBZA can be prepared efficiently with a yield of 40–50%. The uptake of [18F]FPBZA by B16F0 melanoma cells was significantly higher than those by A375 tumor cells and NB-DNJ-pretreated B16F0 melanoma cells. B16F0 melanoma displayed prominent uptake of [18F]FPBZA at 2 h (7.81 ± 0.82 %ID/g), compared with A375 tumor and inflammation lesion (3.00 ± 0.71 and 1.67 ± 0.56 %ID/g, resp.). [18F]FPBZA microPET scan clearly delineated B16F0 melanoma but not A375 tumor and inflammation lesion. In mice bearing pulmonary metastases, the lung radioactivity reached 4.77 ± 0.36 %ID/g at 2 h (versus 1.16 ± 0.23 %ID/g in normal mice). Conclusions. Our results suggested that [18F]FPBZA PET would provide a promising and specific approach for the detection of primary and metastatic melanoma lesions. PMID:25254219

  18. Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma.

    PubMed

    Castaldi, P; Leccisotti, L; Bussu, F; Miccichè, F; Rufini, V

    2013-02-01

    The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of (18)F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of (18)F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of (18)F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of (18)F-FDG.

  19. Added value of 18F-FDG PET/CT in diagnosing infected hip prosthesis.

    PubMed

    Kwee, Robert M; Broos, Wouter Am; Brans, Boudewijn; Walenkamp, Geert Him; Geurts, Jan; Weijers, René E

    2018-05-01

    Background The diagnosis of infected hip prosthesis is frequently not straightforward yet very important as it changes treatment. Purpose To retrospectively investigate the added value of 18F-FDG PET/CT to conventional tests including radiography, erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) testing, and joint aspiration, in diagnosing infected hip prosthesis. Material and Methods Seventy-eight hip prostheses of 78 patients (55% men; mean age = 66.5 years; age range = 30-85 years) with non-specific clinical presentation, i.e. no abscess or sinus tract communicating with the joint space at clinical examination, were analyzed. Cultures of intra-articular fluid and peri-implant tissues after revision surgery or clinical follow-up ≥6 months served as gold standard. Areas under the receiver operating characteristic curves (AUCs) of radiography, ESR/CRP testing, aspiration culture, and white blood cell (WBC) count without and with the addition of 18F-FDG PET/CT were compared. Results The addition of 18F-FDG PET/CT increased AUCs: for radiography with 0.212, P = 0.001; for ESR/CRP testing with 0.076, P = 0.072; for aspiration culture with 0.126, P = 0.032; and for aspiration WBC count with 0.191, P = 0.035. Conclusion This study shows that 18F-FDG PET/CT adds to individual conventional tests in diagnosing infected hip prosthesis. It may improve the preoperative planning and should therefore be considered in the diagnostic work-up. Future studies should define the exact place of 18F-FDG PET/CT in the diagnostic work-up of periprosthetic joint infection.

  20. N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

    PubMed

    Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

    2003-12-01

    There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in

  1. Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

    PubMed

    Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

    2016-01-01

    With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Initial in vivo PET imaging of 5-HT1A receptors with 3-[18F]mefway

    PubMed Central

    Wooten, Dustin W; Hillmer, Ansel T; Murali, Dhanabalan; Barnhart, Todd E; Thio, Joanne P; Bajwa, Alisha K; Bonab, Ali A; Normandin, Marc D; Schneider, Mary L; Mukherjee, Jogeshwar; Christian, Bradley T

    2014-01-01

    4-trans-[18F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[18F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[18F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[18F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[18F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[18F]mefway to 4-trans-[18F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[18F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[18F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[18F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[18F]mefway suggests the lower BPND of 3-[18F]mefway is due to a lower affinity. The lower affinity of 3-[18F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained. PMID:25143866

  3. 18F-FDG PET/CT in gastric MALT lymphoma: a bicentric experience.

    PubMed

    Albano, Domenico; Bertoli, Mattia; Ferro, Paola; Fallanca, Federico; Gianolli, Luigi; Picchio, Maria; Giubbini, Raffaele; Bertagna, Francesco

    2017-04-01

    The role of 18F-FDG-PET/CT in evaluating gastric MALT lymphoma is still controversial. In the literature the detection rate of 18F-FDG-PET/CT in patients with gastric MALT lymphoma is variable, and the reason for this heterogeneity is not still clear. Our aim was to investigate the particular metabolic behavior of these lymphoma. Sixty-nine patients (26 female, 43 male) with histologically confirmed gastric MALT lymphoma who underwent a 18F-FDG-PET/CT for initial staging from two centers were included. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio and compared with Ann Arbor stage, epidemiological (age, sex), histological (presence of gastritis, ulcer, H. pylori infection, plasmacytic differentiation, Ki-67 index), and morphological (tumor size, superficial lesions or mass-forming) characteristics. Thirty-six patients (52 %) had positive PET/CT (average SUVmax was 9±6.7; lesion-to-liver SUVmax ratio 3.7±2.6, lesion-to-blood pool SUVmax ratio 4.8±3.3) at the corresponding gastric lesion; the remaining 33 were not 18F-FDG-avid. In the univariate analysis, 18F-FDG avidity was significantly associated with morphological features (mass forming p<0.001 and high maximum diameter p<0.001), Ann Arbor stage (p=0.010), and Ki67 index (p<0.001) and not correlated with age, sex, presence of gastritis, ulcer, Helicobacter pylori infection, and plasmacytic differentiation. In the multivariate analysis, the correlations with gross morphological appearance, Ann Arbor stage, and Ki-67 score were confirmed. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio correlated significantly only with Ki67 index (p=0.047; p=0.012; p=0.042). 18F-FDG avidity was noted in 52 % of gastric MALT lymphoma and this avidity is correlated with gross morphological characteristics, tumor stage, and Ki-67 index. SUVmax, lesion

  4. Optimized in vivo detection of dopamine release using 18F-fallypride PET.

    PubMed

    Ceccarini, Jenny; Vrieze, Elske; Koole, Michel; Muylle, Tom; Bormans, Guy; Claes, Stephan; Van Laere, Koen

    2012-10-01

    The high-affinity D(2/3) PET radioligand (18)F-fallypride offers the possibility of measuring both striatal and extrastriatal dopamine release during activation paradigms. When a single (18)F-fallypride scanning protocol is used, task timing is critical to the ability to explore both striatal and extrastriatal dopamine release simultaneously. We evaluated the sensitivity and optimal timing of task administration for a single (18)F-fallypride PET protocol and the linearized simplified reference region kinetic model in detecting both striatal and extrastriatal reward-induced dopamine release, using human and simulation studies. Ten healthy volunteers underwent a single-bolus (18)F-fallypride PET protocol. A reward responsiveness learning task was initiated at 100 min after injection. PET data were analyzed using the linearized simplified reference region model, which accounts for time-dependent changes in (18)F-fallypride displacement. Voxel-based statistical maps, reflecting task-induced D(2/3) ligand displacement, and volume-of-interest-based analysis were performed to localize areas with increased ligand displacement after task initiation, thought to be proportional to changes in endogenous dopamine release (γ parameter). Simulated time-activity curves for baseline and hypothetical dopamine release functions (different peak heights of dopamine and task timings) were generated using the enhanced receptor-binding kinetic model to investigate γ as a function of these parameters. The reward task induced increased ligand displacement in extrastriatal regions of the reward circuit, including the medial orbitofrontal cortex, ventromedial prefrontal cortex, and dorsal anterior cingulate cortex. For task timing of 100 min, ligand displacement was found for the striatum only when peak height of dopamine was greater than 240 nM, whereas for frontal regions, γ was always positive for all task timings and peak heights of dopamine. Simulation results for a peak height of

  5. Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

    PubMed

    Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

    2017-10-01

    Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

  6. 18F-FDG PET and PET/CT in the Localization and Characterization of Lesions in Patients with Ovarian Cancer.

    PubMed

    Caprio, M G; Capacchione, D; Mainolfi, C; Spera, A M; Salvatore, B; Cella, L; Salvatore, M; Pace, L

    2012-01-01

    The aim was to compare the imaging findings of (18)F-fluorodeoxyglucose ((18)F-FDG) PET and integrated PET/CT in patients with primary, recurrent or metastatic ovarian cancer. 21 women with ovarian cancer were evaluated. All patients had a integrated PET/CT scan. Localization, infiltration and uptake intensity of [(18)F]FDG were evaluated on PET and PET/CT. The certainty of localisation and characterisation was scored on a 3 point scale (L1 definite localisation; L2 probable localisation; L3 uncertain localisation; C1 benign; C2 equivocal; C3 malignant). PET scored as L1 54 lesions (44%), as L2 51 (42%), and as L3 17 (14%). On the other hand, PET/CT scored as L1 120 lesions (98%), as L2 2 (2%), and none as L3. Thus PET/CT allowed a better localization in 54% of lesions. Moreover, PET scored as C1 25 lesions (20%), as C2 62 (51%), and as C3 35 (29%). On the other hand, PET/CT scored as C1 57 lesions (47%), as C2 13 (11%), and as C3 52 (42%). Thus PET/CT allowed a sensible reduction in the number of equivocal lesions (40%). Even when patients were subgrouped on the basis of clinical stage of the disease, PET/CT was capable of better definition of the lesions either for localization and for characterization. In patients with ovarian cancer, PET/CT allows better anatomical localisation of pathologic uptake providing high accuracy for staging and restaging of ovarian cancer when compared with PET alone.

  7. Whole-body MRI versus 18F-FDG PET/CT for pretherapeutic assessment and staging of lymphoma: a meta-analysis.

    PubMed

    Wang, Danyang; Huo, Yanlei; Chen, Suyun; Wang, Hui; Ding, Yingli; Zhu, Xiaochun; Ma, Chao

    2018-01-01

    18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) is the reference standard in staging of 18 F-FDG-avid lymphomas; however, there is no recommended functional imaging modality for indolent lymphomas. Therefore, we aimed to compare the performance of whole-body magnetic resonance imaging (WB-MRI) with that of 18 F-FDG PET/CT for lesion detection and initial staging in patients with aggressive or indolent lymphoma. We searched the MEDLINE, EMBASE, and CENTRAL databases for studies that compared WB-MRI with 18 F-FDG PET/CT for lymphoma staging or lesion detection. The methodological quality of the studies was assessed using version 2 of the "Quality Assessment of Diagnostic Accuracy Studies" tool. The pooled staging accuracy ( μ ) of WB-MRI and 18 F-FDG PET/CT for initial staging and for assessing possible heterogeneity ( χ 2 ) across studies were calculated using commercially available software. Eight studies comprising 338 patients were included. In terms of staging, the meta-analytic staging accuracies of WB-MRI and 18 F-FDG PET/CT for Hodgkin lymphoma and aggressive non-Hodgkin lymphoma (NHL) were 98% (95% CI, 94%-100%) and 98% (95% CI, 94%-100%), respectively. The pooled staging accuracy of 18 F-FDG PET/CT dropped to 87% (95% CI, 72%-97%) for staging in patients with indolent lymphoma, whereas that of WB-MRI remained 96% (95% CI, 91%-100%). Subgroup analysis indicated an even lower staging accuracy of 18 F-FDG PET/CT for staging of less FDG-avid indolent NHLs (60%; 95% CI, 23%-92%), in contrast to the superior performance of WB-MRI (98%; 95% CI, 88%-100%). WB-MRI is a promising radiation-free imaging technique that may serve as a viable alternative to 18 F-FDG PET/CT for staging of 18 FDG-avid lymphomas, where 18 F-FDG PET/CT remains the standard of care. Additionally, WB-MRI seems a less histology-dependent functional imaging test than 18 F-FDG PET/CT and may be the imaging test of choice for staging of indolent NHLs

  8. Preclinical characterization of 18F-MAA, a novel PET surrogate of 99mTc-MAA.

    PubMed

    Wu, Shih-Yen; Kuo, Jia-Wei; Chang, Tien-Kuei; Liu, Ren-Shen; Lee, Rheun-Chuan; Wang, Shyh-Jen; Lin, Wuu-Jyh; Wang, Hsin-Ell

    2012-10-01

    (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) scintigraphy scan is routinely performed for lung perfusion imaging and for the assessment of in vivo distribution of (90)Y-labeled SIR-Spheres prior to selective internal radiation treatment for hepatocellular carcinoma. Positron emission tomography (PET) imaging is superior to gamma scintigraphy in terms of sensitivity, spatial resolution and accuracy of quantification. This study reported that (18)F-labeled macroaggregated albumin ((18)F-MAA) is an ideal PET imaging surrogate for (99m)Tc-MAA. (18)F-MAA was prepared from the commercial MAA kit via a one-step conjugation with N-succinimidyl 4-(18)F-fluorobenzoate ((18)F-SFB). The biodistribution study and microPET/microSPECT imaging were conducted in normal SD rats after intravenous injection of (18)F-MAA/(99m)Tc-MAA. A comparison study of these two radiotracers was performed after co-injection via the intrahepatic arterial in a N1S1 hepatoma-bearing SD rat model. The optimal condition for (18)F-MAA preparation is coupling MAA (0.5mg) with (18)F-SFB at 45°C for 5 min in a phosphate buffer of pH 8.5. (18)F-MAA was prepared in 60 min with high radiochemical yield (30%-35%) and high radiochemical purity (>95%). The in vivo distribution of (18)F-MAA after intravenous injection meets the specifications of MAA depicted in European Pharmacopeia. Our study demonstrated excellent correlation between (18)F-MAA and (99m)Tc-MAA in the regional distribution of tumor, liver and lungs (R(2)=0.965, 0.886 and 0.991, respectively), and also in the tumor-to-liver and tumor-to-lungs ratio (R(2)=0.965 and 0.987, respectively) in a N1S1 hepatoma-bearing SD rat model. The organ uptakes derived from animal PET/CT and SPECT/CT imaging after administration of these two tracers were in accordance with those obtained in the distribution studies. Starting from commercial MAA kit, an efficient preparation of (18)F-MAA was successfully established. Highly correlated, almost parallel

  9. Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas.

    PubMed

    Youland, Ryan S; Pafundi, Deanna H; Brinkmann, Debra H; Lowe, Val J; Morris, Jonathan M; Kemp, Bradley J; Hunt, Christopher H; Giannini, Caterina; Parney, Ian F; Laack, Nadia N

    2018-05-01

    Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%, M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

  10. Influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer.

    PubMed

    López, Escarlata; Lazo, Antonio; Gutiérrez, Antonio; Arregui, Gregorio; Núñez, Isabel; Sacchetti, Antonio

    2015-01-01

    To evaluate the influence of (11)C-choline PET/CT on radiotherapy planning in prostate cancer patients. Precise information on the extension of prostate cancer is crucial for the choice of an appropriate therapeutic strategy. (11)C-choline positron emission tomography ((11)C-choline PET/CT) has two roles in radiation oncology (RT): (1) patient selection for treatment and (2) target volume selection and delineation. In conjunction with high-accuracy techniques, it might offer an opportunity of dose escalation and better tumour control while sparing healthy tissues. We carried out a retrospective study in order to analyse RT planning modification based on (11)C-choline PET/CT in 16 prostate cancer patients. Patients were treated with hypofractionated step-and-shoot Intensity Modulated Radiotherapy (IMRT), or Volumetric Modulated Arc Therapy (VMAT), and a daily cone-beam CT for Image Guided Radiation Therapy (IGRT). All patients underwent a (11)C-choline-PET/CT scan prior to radiotherapy. In 37.5% of cases, a re-delineation and new dose prescription occurred. Data show good preliminary clinical results in terms of biochemical control and toxicity. No gastrointestinal (GI)/genitourinary (GU) grade III toxicities were observed after a median follow-up of 9.5 months. In our experience, concerning the treatment of prostate cancer (PCa), (11)C-choline PET/CT may be helpful in radiotherapy planning, either for dose escalation or exclusion of selected sites.

  11. ¹⁸F-choline positron emission tomography/computed tomography-driven high-dose salvage radiation therapy in patients with biochemical progression after radical prostatectomy: feasibility study in 60 patients.

    PubMed

    D'Angelillo, Rolando M; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A; Trodella, Luca E; Fiore, Michele; Gallucci, Michele; Maini, Carlo L; Trodella, Lucio

    2014-10-01

    To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic (18)F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. At early follow-up, (18)F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies.

    PubMed

    Uslu, Lebriz; Donig, Jessica; Link, Michael; Rosenberg, Jarrett; Quon, Andrew; Daldrup-Link, Heike E

    2015-02-01

    Successful management of solid tumors in children requires imaging tests for accurate disease detection, characterization, and treatment monitoring. Technologic developments aim toward the creation of integrated imaging approaches that provide a comprehensive diagnosis with a single visit. These integrated diagnostic tests not only are convenient for young patients but also save direct and indirect health-care costs by streamlining procedures, minimizing hospitalizations, and minimizing lost school or work time for children and their parents. (18)F-FDG PET/CT is a highly sensitive and specific imaging modality for whole-body evaluation of pediatric malignancies. However, recent concerns about ionizing radiation exposure have led to a search for alternative imaging methods, such as whole-body MR imaging and PET/MR. As we develop new approaches for tumor staging, it is important to understand current benchmarks. This review article will synthesize the current literature on (18)F-FDG PET/CT for tumor staging in children, summarizing questions that have been solved and providing an outlook on unsolved avenues. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  13. Role of 18F-fluoride PET/CT in the assessment of multiple myeloma: initial experience.

    PubMed

    Nishiyama, Yuji; Tateishi, Ukihide; Shizukuishi, Kazuya; Shishikura, Ayako; Yamazaki, Etsuko; Shibata, Hiroto; Yoneyama, Tomohiro; Ishigatsubo, Yoshiaki; Inoue, Tomio

    2013-01-01

    The aim of this study was to report our early experience with (18)F-fluoride PET/CT for detecting lesions and evaluate the usefulness of this modality in the assessment of multiple myeloma (MM). (18)F-fluoride PET/CT and (99m)Tc-MDP bone scintigraphy (BS) studies from 7 myeloma patients (4 male and 3 female, mean age 55 years) diagnosed according to standard criteria were reviewed retrospectively. Two reviewers visually and quantitatively analyzed the images and recorded their findings after reaching a consensus. Diagnostic certainty regarding the presence or absence of myeloma lesions was evaluated according to the reference standard consisting of whole-body magnetic resonance imaging and whole-body X-ray. A total of 93 affected areas were definite according to the reference standard. Of these, 83 affected areas (89 %) were identified on (18)F-fluoride PET/CT, whereas 54 affected areas (58 %) were found on BS. Mean SUVmax in the affected areas was 9.8 ± 3.2 (standard deviation) ranging from 5.0 to 21.2. A total of s17 lesions with bone fracture were also detected by (18)F-fluoride PET/CT and 2 lesions (12 %) were negative on BS. Our result showed that (18)F-fluoride PET was a possible modality to detect areas of lesions in patients with MM.

  14. 18F-FDG PET/CT and PET/MRI Perform Equally Well in Cancer: Evidence from Studies on More Than 2,300 Patients

    PubMed Central

    Spick, Claudio; Herrmann, Ken; Czernin, Johannes

    2016-01-01

    18F-FDG PET/CT has become the reference standard in oncologic imaging against which the performance of other imaging modalities is measured. The promise of PET/MRI includes multiparametric imaging to further improve diagnosis and phenotyping of cancer. Rather than focusing on these capabilities, many investigators have examined whether 18F-FDG PET combined with mostly anatomic MRI improves cancer staging and restaging. After a description of PET/MRI scanner designs and a discussion of technical and operational issues, we review the available literature to determine whether cancer assessments are improved with PET/MRI. The available data show that PET/MRI is feasible and performs as well as PET/CT in most types of cancer. Diagnostic advantages may be achievable in prostate cancer and in bone metastases, whereas disadvantages exist in lung nodule assessments. We conclude that 18F-FDG PET/MRI and PET/CT provide comparable diagnostic information when MRI is used simply to provide the anatomic framework. Thus, PET/MRI could be used in lieu of PET/CT if this approach becomes economically viable and if reasonable workflows can be established. Future studies should explore the multiparametric potential of MRI. PMID:26742709

  15. (18)F-alfatide II and (18)F-FDG dual-tracer dynamic PET for parametric, early prediction of tumor response to therapy.

    PubMed

    Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O; Xie, Qingguo; Li, Quanzheng; Eden, Henry S; Niu, Gang; Chen, Xiaoyuan

    2014-01-01

    A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with (18)F-alfatide II ((18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) and (18)F-FDG for parametric monitoring of tumor responses to therapy. We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with (18)F-alfatide II, followed 40 min later by (18)F-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of (18)F-alfatide II for the 40 min before (18)F-FDG injection and then extrapolated to 90 min. The (18)F-FDG tumor time-activity curve was isolated from the 90-min dual-tracer tumor time-activity curve by subtracting the fitted (18)F-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the (18)F-alfatide II binding potential (Bp = k3/k4) and volume of distribution (VD) and (18)F-FDG influx rate ((K1 × k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. The transport and binding rate parameters K1-k3 of (18)F-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single-tracer scan (R(2) > 0.95). Compared with the results of single-tracer PET imaging, (18)F-FDG tumor uptake and influx were recovered well from dual-tracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of (18)F-alfatide II

  16. 18F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study.

    PubMed

    Blanchet, Elise M; Taieb, David; Millo, Corina; Martucci, Victoria; Chen, Clara C; Merino, Maria; Herscovitch, Peter; Pacak, Karel

    2015-12-01

    (18)F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare (18)F-FLT uptake with (18)F-FDG PET/CT, and to evaluate classic factors of aggressiveness. Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with (18)F-FDG and (18)F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUVmax) for both tracers. (18)F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs (SDHB-mutated status, lesion size, dopaminergic phenotype) and with (18)F-FDG uptake. In 12 patients, 77 lesions were assessed. All lesions had low (18)F-FLT uptake (median SUVmax, 2.25; range, 0.7-4.5). There was no apparent superiority of (18)F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high (18)F-FDG uptake (median SUVmax, 10.8; range, 1.1-79.0) contrasting with low (18)F-FLT uptake. This study suggests that PHEOs/PGLs-even those that progress-do not exhibit intense (18)F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of (18)F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal

  17. 18F-Alfatide II and 18F-FDG Dual Tracer Dynamic PET for Parametric, Early Prediction of Tumor Response to Therapy

    PubMed Central

    Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O.; Xie, Qingguo; Li, Quanzheng; Eden, Henry S.; Niu, Gang; Chen, Xiaoyuan

    2014-01-01

    A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor’s status under quasi-constant conditions. This study aims to investigate the utility of dual-tracer dynamic PET imaging with 18F-Alfatide II (18F-AlF-NOTA-E[PEG4-c(RGDfk)]2) and 18F-FDG for parametric monitoring of tumor responses to therapy. Methods We administered doxorubicin to one group of athymic nude mice with U87MG tumors and Abraxane to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting by injecting the mice via tail vein catheters with 18F-Alfatide II, followed 40 minutes later by 18F-FDG. To achieve signal separation of the two tracers, we fit a three-compartment reversible model to the time activity curve (TAC) of 18F-Alfatide II for the 40 min prior to 18F-FDG injection, and then extrapolated to 90 min. The 18F-FDG tumor TAC was isolated from the 90 min dual tracer tumor TAC by subtracting the fitted 18F-Alfatide II tumor TAC. With separated tumor TACs, the 18F-Alfatide II binding potential (Bp=k3/k4) and volume of distribution (VD), and 18F-FDG influx rate ((K1×k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single tracer imaging and to monitor therapeutic response. Results The transport and binding rate parameters K1-k3 of 18F-Alfatide II, calculated from the first 40 min of dual tracer dynamic scan, as well as Bp and VD, correlated well with the parameters from the 60 min single tracer scan (R2 > 0.95). Compared with the results of single tracer PET imaging, FDG tumor uptake and influx were recovered well from dual tracer imaging. Upon doxorubicin treatment, while no significant changes in static tracer uptake values of 18F-Alfatide II or 18F-FDG were observed, both 18F-Alfatide II Bp and 18F-FDG influx from kinetic

  18. Use of [18F]FDG PET to Monitor The Development of Cardiac Allograft Rejection

    PubMed Central

    Daly, Kevin P.; Dearling, Jason L. J.; Seto, Tatsuichiro; Dunning, Patricia; Fahey, Frederic; Packard, Alan B.; Briscoe, David M.

    2014-01-01

    Background Positron Emission Tomography (PET) has the potential to be a specific, sensitive and quantitative diagnostic test for transplant rejection. To test this hypothesis, we evaluated 18F-labeled fluorodeoxyglucose ([18F]FDG) and 13N-labeled ammonia ([13N]NH3) small animal PET imaging in a well-established murine cardiac rejection model. Methods Heterotopic transplants were performed using minor MHC mismatched B6.C-H2bm12 donor hearts in C57BL/6(H-2b) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls. [18F]FDG PET imaging was performed weekly between post-transplant days 7 and 42 and the percent injected dose was computed for each graft. [13N]NH3 imaging was performed to evaluate myocardial perfusion. Results There was a significant increase in [18F]FDG uptake in allografts from day 14 to day 21 (1.6% to 5.2%; P<0.001) and uptake in allografts was significantly increased on post-transplant days 21 (5.2% vs. 0.9%; P=0.005) and 28 (4.8% vs. 0.9%; P=0.006) compared to isograft controls. Furthermore, [18F]FDG uptake correlated with an increase in rejection within allografts between days 14 and 28 post-transplant. Finally, the uptake of [13N]NH3 was significantly lower relative to the native heart in allografts with chronic vasculopathy compared to isograft controls on day 28 (P=0.01). Conclusions PET imaging with [18F]FDG can be used following transplantation to monitor the evolution of rejection. In addition, decreased uptake of [13N]NH3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [18F]FDG and [13N]NH3 PET imaging could be used as a non-invasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients. PMID:25675207

  19. [18F]-2-Fluoro-2-Deoxy-D-glucose-PET Assessment of Cervical Cancer.

    PubMed

    Viswanathan, Chitra; Faria, Silvana; Devine, Catherine; Patnana, Madhavi; Sagebiel, Tara; Iyer, Revathy B; Bhosale, Priya R

    2018-04-01

    This article provides an overview of PET in cervical cancer, primarily with regard to the use of 18 F-2-fluoro-2-deoxy-d-glucose-PET/computed tomography. A brief discussion of upcoming technologies, such as PET/MR imaging, is presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A novel approach to breast cancer diagnosis via PET imaging of microcalcifications using 18F-NaF

    PubMed Central

    Wilson, George H.; Gore, John C.; Yankeelov, Thomas E.; Barnes, Stephanie; Peterson, Todd E.; True, Jarrod M.; Shokouhi, Sepideh; McIntyre, J. Oliver.; Sanders, Melinda; Abramson, Vandana; Ngyuen, The-Quyen; Mahadevan-Jansen, Anita; Tantawy, Mohammed N.

    2015-01-01

    Rationale Current radiological methods for diagnosing breast cancer detect specific morphological features of solid tumors and/or any associated calcium deposits. These deposits originate from an early molecular microcalcification process which consists of two types: type 1 is calcium oxylate (CO) and type II is carbonated calcium hydroxyapetite (HAP). Type I microcalcifications are mainly associated with benign tumors while type II have been shown to be produced, internally, by malignant cells. No current non-invasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. 18F-NaF PET has been solely used for bone imaging by targeting the bone HAP. In this work, we provide preliminary evidence that 18F-NaF PET imaging can be used to detect breast cancer by targeting the HAP lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio, while delineating tumors from inflammation. METHODS Mice were injected with approximately 106 MDA-MB-231 cells subcutaneously and imaged with 18F-NaF PET/CT in a 120 min dynamic sequence when the tumors reached a size of ~250 mm3. Regions-of-interest (ROIs) were drawn around the tumor, muscle, and bone. The concentration of the radiotracer within those ROIs were compared to one another. For comparison to inflammation, rats with inflammatory paws were subjected to 18F-NaF PET imaging. RESULTS Tumor uptake of 18F− was significantly higher (p<0.05) than muscle uptake where the tumor-to-muscle ratio was ~3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of 18F− was observed in the rat inflamed tissue. Lack of HAP in the inflamed tissue was verified histologically. CONCLUSIONS This study

  1. PET/CT with 18F-FDG- and 18F-FBEM-labeled leukocytes for metabolic activity and leukocyte recruitment monitoring in a mouse model of pulmonary fibrosis.

    PubMed

    Bondue, Benjamin; Sherer, Félicie; Van Simaeys, Gaetan; Doumont, Gilles; Egrise, Dominique; Yakoub, Yousof; Huaux, François; Parmentier, Marc; Rorive, Sandrine; Sauvage, Sébastien; Lacroix, Simon; Vosters, Olivier; De Vuyst, Paul; Goldman, Serge

    2015-01-01

    Idiopathic pulmonary fibrosis is characterized by a progressive and irreversible respiratory failure. Validated noninvasive methods able to assess disease activity are essential for prognostic purposes as well as for the evaluation of emerging antifibrotic treatments. C57BL/6 mice were used in a murine model of pulmonary fibrosis induced by an intratracheal instillation of bleomycin (control mice were instilled with a saline solution). At different times after instillation, PET/CT with (18)F-FDG- or (18)F-4-fluorobenzamido-N-ethylamino-maleimide ((18)F-FBEM)-labeled leukocytes was performed to assess metabolic activity and leukocyte recruitment, respectively. In bleomycin-treated mice, a higher metabolic activity was measured on (18)F-FDG PET/CT scans from day 7 to day 24 after instillation, with a peak of activity measured at day 14. Of note, lung mean standardized uptake values correlated with bleomycin doses, histologic score of fibrosis, lung hydroxyproline content, and weight loss. Moreover, during the inflammatory phase of the model (day 7), but not the fibrotic phase (day 23), bleomycin-treated mice presented with an enhanced leukocyte recruitment as assessed by (18)F-FBEM-labeled leukocyte PET/CT. Autoradiographic analysis of lung sections and CD45 immunostaining confirm the higher and early recruitment of leukocytes in bleomycin-treated mice, compared with control mice. (18)F-FDG- and (18)F-FBEM-labeled leukocyte PET/CT enable monitoring of metabolic activity and leukocyte recruitment in a mouse model of pulmonary fibrosis. Implications for preclinical evaluation of antifibrotic therapy are expected. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21 patients.

    PubMed

    Dumarey, Nicolas; Egrise, Dominique; Blocklet, Didier; Stallenberg, Bernard; Remmelink, Myriam; del Marmol, Véronique; Van Simaeys, Gaëtan; Jacobs, Frédérique; Goldman, Serge

    2006-04-01

    The aim of this study was to assess the feasibility and the potential role of PET/CT with (18)F-FDG-labeled autologous leukocytes in the diagnosis and localization of infectious lesions. Twenty-one consecutive patients with suspected or documented infection were prospectively evaluated with whole-body PET/CT 3 h after injection of autologous (18)F-FDG-labeled leukocytes. Two experienced nuclear medicine physicians who were unaware of the clinical end-diagnosis reviewed all PET/CT studies. A visual score (0-3)-according to uptake intensity-was used to assess studies. The results of PET/CT with (18)F-FDG-labeled white blood cell ((18)F-FDG-WBC) assessment were compared with histologic or biologic diagnosis in 15 patients and with clinical end-diagnosis after complete clinical work-up in 6 patients. Nine patients had fever of unknown etiology, 6 patients had documented infection but with unknown extension of the infectious disease, 4 patients had a documented infection with unfavorable evolution, and 2 patients had a documented infection with known extension. The best trade-off between sensitivity and specificity was obtained when a visual score of >or=2 was chosen to identify increased tracer uptake as infection. With this threshold, sensitivity, specificity, and accuracy were each 86% on a patient-per-patient basis and 91%, 85%, and 90% on a lesion-per-lesion basis. In this small group of patients, the absence of areas with increased WBC uptake on WBC PET/CT had a 100% negative predictive value. Hybrid (18)F-FDG-WBC PET/CT was found to have a high sensitivity and specificity for the diagnosis of infection. It located infectious lesions with a high precision. In this small series, absence of areas with increased uptake virtually ruled out the presence of infection. (18)F-FDG-WBC PET/CT for infection detection deserves further investigation in a larger prospective series.

  3. High (18)F-FDG uptake in urinary calculi on PET/CT: An unrecognized non-malignant accumulation.

    PubMed

    Fu, Zhanli; Li, Ziao; Huang, Jia; Zhang, Jin; Liu, Meng; Li, Qian; Li, Yi

    2016-08-01

    To assess the high (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in urinary calculi on positron-emission tomography/computed tomography (PET/CT). In this study, (18)F-FDG PET/CT examinations were retrospectively reviewed from November 2013 to February 2016 in a single center, and patients with high (18)F-FDG uptake in urinary calculi were identified. The following data were collected from each patient, including age, sex, primary disease, method to verify the urinary calculus, and imaging characteristics of the calculus. A total of 2758 PET/CT studies (2567 patients) were reviewed, and 52 patients with urinary calculi were identified, in which 6 (11.5%, 6/52) patients (5 males, 1 female, age 34-73 years, median age 60.5 years) demonstrated high (18)F-FDG uptake in the urinary calculi. Among the 6 patients, 3 patients had bladder calculi, 2 patients had renal calculi, and 1 patient had both bladder and renal calculi. The size of the urinary calculi varied from sandy to 19mm on CT. The maximal Hounsfield units of the calculi ranged from 153 to 1078. The SUVmax of the calculi on the routine PET/CT scan ranged from 11.7 to 143.0. Delayed PET/CT scans were performed on 4 patients, which showed the calculi SUVmax increasing in 2 patients, while decreasing in the other 2 patients. One patient with bladder calculus underwent a follow-up PET/CT, which showed enlargement of the calculus as well as the increased SUVmax. This study shows an uncommon high (18)F-FDG uptake in urinary calculi. Recognition of this non-malignant accumulation in urinary calculi is essential for correct interpretation of PET/CT findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. (S)-4-(3-18F-fluoropropyl)-L-glutamic acid: an 18F-labeled tumor-specific probe for PET/CT imaging--dosimetry.

    PubMed

    Smolarz, Kamilla; Krause, Bernd Joachim; Graner, Frank-Philipp; Wagner, Franziska Martina; Hultsch, Christina; Bacher-Stier, Claudia; Sparks, Richard B; Ramsay, Susan; Fels, Lüder M; Dinkelborg, Ludger M; Schwaiger, Markus

    2013-06-01

    The glutamic acid derivative (S)-4-(3-(18)F-Fluoropropyl)-l-glutamic acid ((18)F-FSPG, alias BAY 94-9392), a new PET tracer for the detection of malignant diseases, displayed promising results in non-small cell lung cancer patients. The aim of this study was to provide dosimetry estimates for (18)F-FSPG based on human whole-body PET/CT measurements. (18)F-FSPG was prepared by a fully automated 2-step procedure and purified by a solid-phase extraction method. PET/CT scans were obtained for 5 healthy volunteers (mean age, 59 y; age range, 51-64 y; 2 men, 3 women). Human subjects were imaged for up to 240 min using a PET/CT scanner after intravenous injection of 299 ± 22.5 MBq of (18)F-FSPG. Image quantification, time-activity data modeling, estimation of normalized number of disintegrations, and production of dosimetry estimates were performed using the RADAR (RAdiation Dose Assessment Resource) method for internal dosimetry and in general concordance with the methodology and principles as presented in the MIRD 16 document. Because of the renal excretion of the tracer, the absorbed dose was highest in the urinary bladder wall and kidneys, followed by the pancreas and uterus. The individual organ doses (mSv/MBq) were 0.40 ± 0.058 for the urinary bladder wall, 0.11 ± 0.011 for the kidneys, 0.077 ± 0.020 for the pancreas, and 0.030 ± 0.0034 for the uterus. The calculated effective dose was 0.032 ± 0.0034 mSv/MBq. Absorbed dose to the bladder and the effective dose can be reduced significantly by frequent bladder-voiding intervals. For a 0.75-h voiding interval, the bladder dose was reduced to 0.10 ± 0.012 mSv/MBq, and the effective dose was reduced to 0.015 ± 0.0010 mSv/MBq. On the basis of the distribution and biokinetic data, the determined radiation dose for (18)F-FSPG was calculated to be 9.5 ± 1.0 mSv at a patient dose of 300 MBq, which is of similar magnitude to that of (18)F-FDG (5.7 mSv). The effective dose can be reduced to 4.5 ± 0.30 mSv (at 300 MBq

  5. [18F]-NaF PET/CT imaging in cardiac amyloidosis.

    PubMed

    Van Der Gucht, Axel; Galat, Arnault; Rosso, Jean; Guellich, Aziz; Garot, Jérôme; Bodez, Diane; Plante-Bordeneuve, Violaine; Hittinger, Luc; Dubois-Randé, Jean-Luc; Evangelista, Eva; Sasanelli, Myriam; Chalaye, Julia; Meignan, Michel; Itti, Emmanuel; Damy, Thibaud

    2016-08-01

    Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.

  6. A multicenter clinical trial on the diagnostic value of dual-tracer PET/CT in pulmonary lesions using 3'-deoxy-3'-18F-fluorothymidine and 18F-FDG.

    PubMed

    Tian, Jiahe; Yang, Xiaofeng; Yu, Lijuan; Chen, Ping; Xin, Jun; Ma, Liming; Feng, Huiru; Tan, Yieyin; Zhao, Zhoushe; Wu, Wenkai

    2008-02-01

    Some new radiotracers might add useful information and improve diagnostic confidence of (18)F-FDG imaging in tumors. A multicenter clinical trial was designed to investigate the diagnostic performance of dual-tracer ((18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]) PET/CT in pulmonary nodules. Fifty-five patients underwent dual-tracer imaging in 6 imaging centers using the same models of equipment and standardized protocols. The images were interpreted by a collective group of readers who were unaware of the clinical data. The diagnostic performance using either tracer alone or dual-tracers together, with or without CT, was compared. The histological diagnosis or clinical findings in a 12-mo follow-up period served as the standard of truth. In 16 patients with malignant tumor, 16 with tuberculosis, and 23 with other benign lesions, the sensitivity and specificity of (18)F-FDG and (18)F-FLT were 87.5% and 58.97% and 68.75% and 76.92%, respectively. The combination of dual-tracer PET/CT improved the sensitivity and specificity up to 100% and 89.74%. The 3 subgroups of patients could be best separated when the (18)F-FLT/(18)F-FDG standardized uptake value ratio of 0.4-0.90 was used as the threshold. By reflecting different biologic features, the dual-tracer PET/CT using (18)F-FDG and (18)F-FLT favorably affected the diagnosis of lung nodules.

  7. Diagnostic value of 18F-FDG-PET/CT for the follow-up and restaging of soft tissue sarcomas in adults.

    PubMed

    Kassem, T W; Abdelaziz, O; Emad-Eldin, S

    2017-10-01

    The purpose of this study was to evaluate the clinical utility of 2-[ 18 F] fluoro-2-deoxy-D-glucose ( 18 FDG) positron emission tomography (PET)/computed tomography (CT) ( 18 F-FDG-PET/CT) in the follow-up of adult patients with soft tissue sarcomas. We prospectively evaluated 37 consecutive patients with known soft tissue sarcoma with 18 F-FDG-PET/CT examination for suspected recurrence of disease. They were 21 men and 16 women with a mean age of 49.6±10.6 (SD) years (range, 34-75years). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 18 F-FDG-PET/CT examination were calculated on a per patient basis. 18 F-FDG-PET/CT showed an overall diagnostic accuracy of 91.8%, sensitivity of 90% and a specificity of 100%. The positive predictive value and negative predictive value were 100 and 70%, respectively. The 18 F-FDG-PET/CT interpretations were correct in 34/37 patients (91.8%). Incorrect interpretations occurred in three patients (8.1%). Reasons for false negative findings were low 18 F-FDG uptake of local recurrence in one patient and low 18 F-FDG uptake of subcentimetric inguinal lymph node metastases. 18 F-FDG-PET/CT has a high diagnostic value in the follow-up of patients with soft tissue sarcoma. Copyright © 2017 Editions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  8. Radiolabeled choline PET/CT before salvage lymphadenectomy dissection: a systematic review and meta-analysis.

    PubMed

    Evangelista, Laura; Zattoni, Fabio; Karnes, Robert J; Novara, Giacomo; Lowe, Val

    2016-12-01

    To provide a systematic review of recently published reports and carry out a meta-analysis on the use of radiolabeled choline PET/computed tomography (CT) as a guide for salvage lymph node dissection (sLND) in prostate cancer patients with biochemical recurrence after primary treatments. Bibliographic database searches, from 2005 to May 2015, including Pubmed, Web of Science, and TripDatabase, were performed to find studies that included only patients who underwent sLND after radiolabeled choline PET/CT alone or in combination with other imaging modalities. For the qualitative assessment, all studies including the selected population were considered. Conversely, for the quantitative assessment, articles were included only if absolute numbers of true positive, true negative, false positive, and false negative test results were available or derivable from the text for lymph node metastases. Reviews, clinical reports, and editorial articles were excluded from analyses. Eighteen studies fulfilled the inclusion criteria and were assessed qualitatively. A total of 750 patients underwent radiolabeled choline (such as C-choline or F-choline) PET/CT before sLND. A quantitative evaluation was performed in nine studies. A patient-based, a lesion-based, and a site-based analysis was carried out in nine, four, and five studies, respectively. The pooled sensitivities were 85.3% [95% confidence interval (CI): 78.5-90.3%], 56.2% (95% CI: 41.6-69.7%), 75.3% (95% CI: 56.6-87.7%), and 63.7% (95% CI: 41-81.6%), respectively, for patient-based, lesion-based, pelvic site-based, and retroperitoneal site-based analysis. The pooled positive predictive values (PPVs) were 75% (95% CI: 68-80.9%), 85.8% (95% CI: 66.8-94.8%), 81.2% (95% CI: 70.1-88.9%), and 75.2% (95% CI: 58.7-86.7%), respectively, in the same analyses. High heterogeneities among the studies were found for sensitivities and PPVs ranging between 61.7-93.3% and 60.6-94.5%, respectively. Radiolabeled choline PET/CT has only a

  9. Contribution of 11C-Choline PET/CT in prostate carcinoma biochemical relapse with serum PSA level below 1 ng/ml.

    PubMed

    Gómez-de la Fuente, F J; Martínez-Rodríguez, I; de Arcocha-Torres, M; Quirce, R; Jiménez-Bonilla, J; Martínez-Amador, N; Banzo, I

    11 C-choline PET/CT has demonstrated good results in the restaging of prostate cancer (PCa) with high serum prostate specific antigen (PSA), but its use in patients with low serum PSA is controversial. Our aim was to evaluate the contribution of 11 C-choline PET/CT in patients with PCa, biochemical relapse and PSA <1 ng/ml. Fifty consecutive patients (mean age: 65.9±5.6 years) with biochemical relapse of PCa and serum PSA <1ng/ml were evaluated retrospectively. PET/CT was performed 20min after intravenous administration of 555-740 MBq of 11 C-choline. Minimum follow up time was 30 months. Twenty-one out of 50 patients (42%) had an abnormal 11 C-choline PET/CT. In 7 out of 21 patients (14%) tumor was confirmed (4 in prostatic bed, 4 in pelvic lymph nodes, 2 in mediastinal lymph nodes and one synchronous sigmoid carcinoma), and in all cases the initial therapeutic planning was modified. In 2 patients (4%) subsequent tests diagnosed a benign disease (one sarcoidosis, one tuberculosis sequelae) and in 3 patients (6%) they ruled out pathology. The other 9 patients (18%) had no further assessment (7 mediastinal and 4 pelvic lymph nodes). Twenty-nine out of 50 patients (58%) had a normal PET/CT. At 30 months, follow up recurrence was confirmed only in 2 of these patients. 11 C-choline PET/CT proved its usefulness in demonstrating tumor in 14% of patients with BR of PCa and serum PSA <1ng/ml, with therapeutic implications. In 4% of patients a benign condition was detected. A normal 11 C-choline PET/CT was associated with a very low rate of recurrence at 30 months. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  10. Technologist radiation exposure in routine clinical practice with 18F-FDG PET.

    PubMed

    Guillet, Benjamin; Quentin, Pierre; Waultier, Serge; Bourrelly, Marc; Pisano, Pascale; Mundler, Olivier

    2005-09-01

    The use of 18F-FDG for clinical PET studies increases technologist radiation dose exposure because of the higher gamma-radiation energy of this isotope than of other conventional medical gamma-radiation-emitting isotopes. Therefore, 18F-FDG imaging necessitates stronger radiation protection requirements. The aims of this study were to assess technologist whole-body and extremity exposure in our PET department and to evaluate the efficiency of our radiation protection devices (homemade syringe drawing device, semiautomated injector, and video tracking of patients). Radiation dose assessment was performed for monodose as well as for multidose 18F-FDG packaging with both LiF thermoluminescence dosimeters (TLD) and electronic personal dosimeters (ED) during 5 successive 18F-FDG PET steps (from syringe filling to patient departure). The mean +/- SD total effective doses received by technologists (n = 50) during all of the working steps were 3.24 +/- 2.1 and 3.01 +/- 1.4 microSv, respectively, as measured with ED and TLD (345 +/- 84 MBq injected). These values were confirmed by daily TLD technologist whole-body dose measurements (2.98 +/- 1.8 microSv; 294 +/- 78 MBq injected; n = 48). Finger irradiation doses during preparation of single 18F-FDG syringes were 204.9 +/- 24 and 198.4 +/- 23 microSv with multidose vials (345 +/- 93 MBq injected) and 127.3 +/- 76 and 55.9 +/- 47 microSv with monodose vials (302 +/- 43 MBq injected) for the right hand and the left hand, respectively. The protection afforded by the semiautomated injector, estimated as the ratio of the doses received by TLD placed on the syringe shield and on the external face of the injector, was near 2,000. These results showed that technologist radiation doses in our PET department were lower than those reported in the literature. This finding may be explained by the use of a homemade syringe drawing device, a semiautomated injector, and patient video tracking, allowing a shorter duration of contact between

  11. The usefulness of (18)F-FDG PET/MRI fusion image in diagnosing pancreatic tumor: comparison with (18)F-FDG PET/CT.

    PubMed

    Nagamachi, Shigeki; Nishii, Ryuichi; Wakamatsu, Hideyuki; Mizutani, Youichi; Kiyohara, Shogo; Fujita, Seigo; Futami, Shigemi; Sakae, Tatefumi; Furukoji, Eiji; Tamura, Shozo; Arita, Hideo; Chijiiwa, Kazuo; Kawai, Keiichi

    2013-07-01

    This study aimed at demonstrating the feasibility of retrospectively fused (18)F FDG-PET and MRI (PET/MRI fusion image) in diagnosing pancreatic tumor, in particular differentiating malignant tumor from benign lesions. In addition, we evaluated additional findings characterizing pancreatic lesions by FDG-PET/MRI fusion image. We analyzed retrospectively 119 patients: 96 cancers and 23 benign lesions. FDG-PET/MRI fusion images (PET/T1 WI or PET/T2WI) were made by dedicated software using 1.5 Tesla (T) MRI image and FDG-PET images. These images were interpreted by two well-trained radiologists without knowledge of clinical information and compared with FDG-PET/CT images. We compared the differential diagnostic capability between PET/CT and FDG-PET/MRI fusion image. In addition, we evaluated additional findings such as tumor structure and tumor invasion. FDG-PET/MRI fusion image significantly improved accuracy compared with that of PET/CT (96.6 vs. 86.6 %). As additional finding, dilatation of main pancreatic duct was noted in 65.9 % of solid types and in 22.6 % of cystic types, on PET/MRI-T2 fusion image. Similarly, encasement of adjacent vessels was noted in 43.1 % of solid types and in 6.5 % of cystic types. Particularly in cystic types, intra-tumor structures such as mural nodule (35.4 %) or intra-cystic septum (74.2 %) were detected additionally. Besides, PET/MRI-T2 fusion image could detect extra benign cystic lesions (9.1 % in solid type and 9.7 % in cystic type) that were not noted by PET/CT. In diagnosing pancreatic lesions, FDG-PET/MRI fusion image was useful in differentiating pancreatic cancer from benign lesions. Furthermore, it was helpful in evaluating relationship between lesions and surrounding tissues as well as in detecting extra benign cysts.

  12. 68Ga-PSMA and 11C-Choline comparison using a tri-modality PET/CT-MRI (3.0 T) system with a dedicated shuttle.

    PubMed

    Alonso, Omar; Dos Santos, Gerardo; García Fontes, Margarita; Balter, Henia; Engler, Henry

    2018-01-01

    The aim of this study was to prospectively compare the detection rate of 68 Ga-PSMA versus 11 C-Choline in men with prostate cancer with biochemical recurrence and to demonstrate the added value of a tri-modality PET/CT-MRI system. We analysed 36 patients who underwent both 11 C-Choline PET/CT and 68 Ga-PSMA PET/CT scanning within a time window of 1-2 weeks. Additionally, for the 68 Ga-PSMA scan, we used a PET/CT-MRI (3.0 T) system with a dedicated shuttle, acquiring MRI images of the pelvis. Both scans were positive in 18 patients (50%) and negative in 8 patients (22%). Nine patients were positive with 68 Ga-PSMA alone (25%) and one with 11 C-Choline only (3%). The median detected lesion per patient was 2 for 68 Ga-PSMA (range 0-93) and 1 for 11 C-Choline (range 0-57). Tumour to background ratios in all concordant lesions ( n  = 96) were higher for 68 Ga-PSMA than for 11 C-Choline (110.3 ± 107.8 and 27.5 ± 17.1, mean ± S.D., for each tracer, respectively P  = 0.0001). The number of detected lesions per patient was higher for 11 C-Choline in those with PSA ≥ 3.3 ng/mL, while the number of detected lesions was independent of PSA levels for 68 Ga-PSMA using the same PSA cut-off value. Metastatic pelvic lesions were found in 25 patients (69%) with 68 Ga-PSMA PET/CT, in 18 (50%) with 11 C-Choline PET/CT and in 21 (58%) with MRI (3.0 T). MRI was very useful in detecting recurrence in cases classified as indeterminate by means of PET/CT alone at prostate bed. In patients with prostate cancer with biochemical recurrence 68 Ga-PSMA detected more lesions per patient than 11 C-Choline, regardless of PSA levels. PET/CT-MRI (3.0 T) system is a feasible imaging modality that potentially adds useful relevant information with increased accuracy of diagnosis.

  13. F-18 FDG PET/CT in 26 patients with SAPHO syndrome: a new vision of clinical and bone scintigraphy correlation.

    PubMed

    Sun, Xiaochuan; Li, Chen; Cao, Yihan; Shi, Ximin; Li, Li; Zhang, Weihong; Wu, Xia; Wu, Nan; Jing, Hongli; Zhang, Wen

    2018-05-22

    Whole-body bone scintigraphy (WBBS) and MRI are widely used in assessment of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. However, the value of F-18 fluorodeoxyglucose-positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in SAPHO syndrome was unclear. The aim of this study was to characterize the manifestation of SAPHO syndrome on 18 F-FDG PET/CT and explore its relationship with clinical symptoms and WBBS. Twenty-six patients who suffered from SAPHO syndrome and had undergone whole-body 18 F-FDG PET/CT were recruited in Peking Union Medical College Hospital from 2004 to 2016. Clinical manifestations and laboratory findings were recorded for all patients. Imaging data on 18F-FDG PET/CT and WBBS were collected and analyzed retrospectively. All the 26 patients (20 females and 6 males) exhibited skeletal abnormalities on 18 F-FDG PET/CT. Multiple skeletal lesions affecting the anterior chest wall or spine with low to moderate 18 F-FDG uptake and coexistence of osteolysis and osteosclerosis presented as the typical features of SAPHO syndrome. Sixteen (61.5%) patients had abnormal 18 F-FDG uptake outside the osteoarticular system. PET scan had moderate to substantial agreement with CT and WBBS in revealing lesions in the anterior chest wall and axial skeleton. Nonetheless, the correlation between increased 18 F-FDG uptake and clinical symptoms was weak. SAPHO syndrome exhibits characteristic features on 18 F-FDG PET/CT. It showed comparable capacity in revealing skeletal lesions with bone scintigraphy.

  14. [18F]fluoroethylcholine-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes.

    PubMed

    Würschmidt, Florian; Petersen, Cordula; Wahl, Andreas; Dahle, Jörg; Kretschmer, Matthias

    2011-05-01

    At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. The mean SUV(max) in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUV(max) of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after

  15. 123I-Mibg scintigraphy and 18F-Fdg-Pet imaging for diagnosing neuroblastoma

    PubMed Central

    Bleeker, Gitta; Tytgat, Godelieve Am; Adam, Judit A; Caron, Huib N; Kremer, Leontien Cm; Hooft, Lotty; van Dalen, Elvira C

    2015-01-01

    Background Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood. Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (123I-MIBG), which can be used for imaging the tumour. Moreover, 123I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of 123I-MIBG scintigraphy to detect neuroblastoma varies according to the literature. Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of 123I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of 123I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose (18F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. Objectives Primary objectives: 1.1 To determine the diagnostic accuracy of 123I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 1.2 To determine the diagnostic accuracy of negative 123I-MIBG scintigraphy in combination with 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. Secondary objectives: 2.1 To determine the diagnostic accuracy of 18F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old. 2.2 To compare the diagnostic accuracy of 123I

  16. Value of 18F-FDG PET/CT in diagnosing chronic Q fever in patients with central vascular disease.

    PubMed

    Hagenaars, J C J P; Wever, P C; Vlake, A W; Renders, N H M; van Petersen, A S; Hilbink, M; de Jager-Leclercq, M G L; Moll, F L; Koning, O H J; Hoekstra, C J

    2016-08-01

    The aim of this study is to describe the value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in diagnosing chronic Q fever in patients with central vascular disease and the added value of 18F-FDG PET/CT in the diagnostic combination strategy as described in the Dutch consensus guideline for diagnosing chronic Q fever. 18F-FDG PET/CT was performed in patients with an abdominal aortic aneurysm or aorto-iliac reconstruction and chronic Q fever, diagnosed by serology and positive PCR for Coxiella burnetii DNA in blood and/or tissue (PCR-positive study group). Patients with an abdominal aortic aneurysm or aorto-iliac reconstruction without clinical and serological findings indicating Q fever infection served as a control group. Patients with a serological profile of chronic Q fever and a negative PCR in blood were included in additional analyses (PCR-negative study group). Thirteen patients were evaluated in the PCR-positive study group and 22 patients in the control group. 18F-FDG PET/CT indicated vascular infection in 6/13 patients in the PCR-positive study group and 2/22 patients in the control group. 18F-FDG PET/CT demonstrated a sensitivity of 46% (95% CI: 23-71%), specificity of 91% (95% CI: 71-99%), positive predictive value of 75% (95% CI:41-93%) and negative predictive value of 74% (95% CI: 55-87%). In the PCR-negative study group, 18F-FDG PET/CT was positive in 10/20 patients (50%). The combination of 18F-FDG PET/CT, as an imaging tool for identifying a focus of infection, and Q fever serology is a valid diagnostic strategy for diagnosing chronic Q fever in patients with central vascular disease.

  17. Correction of quantification errors in pelvic and spinal lesions caused by ignoring higher photon attenuation of bone in [{sup 18}F]NaF PET/MR

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schramm, Georg, E-mail: georg.schramm@kuleuven.be; Maus, Jens; Hofheinz, Frank

    Purpose: MR-based attenuation correction (MRAC) in routine clinical whole-body positron emission tomography and magnetic resonance imaging (PET/MRI) is based on tissue type segmentation. Due to lack of MR signal in cortical bone and the varying signal of spongeous bone, standard whole-body segmentation-based MRAC ignores the higher attenuation of bone compared to the one of soft tissue (MRAC{sub nobone}). The authors aim to quantify and reduce the bias introduced by MRAC{sub nobone} in the standard uptake value (SUV) of spinal and pelvic lesions in 20 PET/MRI examinations with [{sup 18}F]NaF. Methods: The authors reconstructed 20 PET/MR [{sup 18}F]NaF patient data setsmore » acquired with a Philips Ingenuity TF PET/MRI. The PET raw data were reconstructed with two different attenuation images. First, the authors used the vendor-provided MRAC algorithm that ignores the higher attenuation of bone to reconstruct PET{sub nobone}. Second, the authors used a threshold-based algorithm developed in their group to automatically segment bone structures in the [{sup 18}F]NaF PET images. Subsequently, an attenuation coefficient of 0.11 cm{sup −1} was assigned to the segmented bone regions in the MRI-based attenuation image (MRAC{sub bone}) which was used to reconstruct PET{sub bone}. The automatic bone segmentation algorithm was validated in six PET/CT [{sup 18}F]NaF examinations. Relative SUV{sub mean} and SUV{sub max} differences between PET{sub bone} and PET{sub nobone} of 8 pelvic and 41 spinal lesions, and of other regions such as lung, liver, and bladder, were calculated. By varying the assigned bone attenuation coefficient from 0.11 to 0.13 cm{sup −1}, the authors investigated its influence on the reconstructed SUVs of the lesions. Results: The comparison of [{sup 18}F]NaF-based and CT-based bone segmentation in the six PET/CT patients showed a Dice similarity of 0.7 with a true positive rate of 0.72 and a false discovery rate of 0.33. The [{sup 18}F]NaF

  18. Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence.

    PubMed

    Steiner, Ch; Vees, H; Zaidi, H; Wissmeyer, M; Berrebi, O; Kossovsky, M P; Khan, H G; Miralbell, R; Ratib, O; Buchegger, F

    2009-01-01

    Contribution of 3-phase 18F-fluorocholine PET/CT in suspected prostate cancer recurrence at early rise of PSA. Retrospective analysis was performed in 47 patients after initial treatment with radiotherapy (n=30) or surgery (n=17). Following CT, 10 minutes list-mode PET acquisition was done over the prostate bed after injection of 300 MBq of 18F-fluorocholine. Three timeframes of 3 minutes each were reconstructed for analysis. All patients underwent subsequent whole body PET/CT. Delayed pelvic PET/CT was obtained in 36 patients. PET/CT was interpreted visually by two observers and SUVmax determined for suspicious lesions. Biopsies were obtained from 13 patients. Biopsies confirmed the presence of cancer in 11 of 13 patients with positive PET for a total of 15 local recurrences in which average SUVmax increased during 14 minutes post injection and marginally decreased in delayed scanning. Conversely inguinal lymph nodes with mild to moderate metabolic activity on PET showed a clearly different pattern with decreasing SUVmax on dynamic images. Three-phase PET/CT contributed to the diagnostic assessment of 10 of 47 patients with biological evidence of recurrence of cancer. It notably allowed the discrimination of confounding blood pool or urinary activity from suspicious hyperactivities. PET/CT was positive in all patients with PSA>or=2 ng/ml (n=34) and in 4/13 patients presenting PSA values<2 ng/ml. 18F-fluorocholine 3-phase PET/CT showed a progressively increasing SUVmax in biopsy confirmed cancer lesions up to 14 minutes post injection while decreasing in inguinal lymph nodes interpreted as benign. Furthermore, it was very useful in differentiating local recurrences from confounding blood pool and urinary activity.

  19. (R)-N-Methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a potential PET imaging agent for norepinephrine transporter

    PubMed Central

    Nguyen, Vivien L.; Pichika, Rama; Bhakta, Paayal H.; Kant, Ritu; Mukherjee, Jogeshwar

    2010-01-01

    A decline of norepinephrine transporter (NET) level is associated with several psychiatric and neurological disorders. Therefore positron emission tomography (PET) imaging agents are greatly desired to study the NET pathway. We have developed a C-fluoropropyl analog of nisoxetine: (R)-N-methyl-3-(3′-[18F]fluoropropyl)phenoxy)-3-phenylpropanamine (18F-MFP3) as a new potential PET radiotracer for NET with the advantage of the longer half-life of fluorine-18 (110 min compared with carbon-11 (20 min). Synthesis of (R)-N-methyl-3-(3′-fluoropropyl)phenoxy)-3-phenylpropanamine (MFP3) was achieved in five steps starting from (S)-N-methyl-3-ol-3-phenylpropanamine in approx. 3–5% overall yields. In vitro binding affinity of nisoxetine and MFP3 in rat brain homogenates labeled with 3H-nisoxetine gave Ki values of 8.02 nM and 23 nM, respectively. For radiosynthesis of 18F-MFP3, fluorine-18 was incorporated into a tosylate precursor, followed by the deprotection of the N-BOC-protected amine group with a 15% decay corrected yield in 2.5 h. Reverse-phase chromatographic purification provided 18F-MFP3 in specific activities of >2000 Ci/mmol. Fluorine-18 labeled 18F-MFP3 has been produced in modest radiochemical yields and in high specific activities. Evaluation of 18F-MFP3 in animal imaging studies is in progress in order to validate this new fluorine-18 radiotracer for PET imaging of NET. PMID:20495670

  20. 18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia.

    PubMed

    Higashi, Tatsuya; Nishii, Ryuichi; Kagawa, Shinya; Kishibe, Yoshihiko; Takahashi, Masaaki; Okina, Tomoko; Suzuki, Norio; Hasegawa, Hiroshi; Nagahama, Yasuhiro; Ishizu, Koichi; Oishi, Naoya; Kimura, Hiroyuki; Watanabe, Hiroyuki; Ono, Masahiro; Saji, Hideo; Yamauchi, Hiroshi

    2018-04-01

    Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2- 18 F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine ( 18 F-FPYBF-2) (Ono et al., J Med Chem 54:2971-9, 2011). The aim of this study was to assess the feasibility of 18 F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using 11 C-Pittsburgh Compound B ( 11 C-PiB). 61 healthy volunteers (age: 53.7 ± 13.1 years old; 19 male and 42 female; age range 24-79) and 55 patients with suspected dementia [Alzheimer's Disease (AD); early AD: n = 19 and moderate stage AD: n = 8, other dementia: n = 9, mild cognitive impairment (MCI): n = 16, cognitively normal: n = 3] for first clinical study underwent static head PET/CT scan using 18 F - FPYBF-2 at 50-70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0-50 min at the same instant. 16 subjects (volunteers: n = 5, patients with dementia: n = 11) (age: 66.3 ± 14.2 years old; 10 males and 6 females) were evaluated for comparative study (50-70 min after injection) using 18 F-FPYBF-2 and 11 C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for 11 C-PiB analysis using cerebellar cortex as control. Studies with healthy volunteers showed that 18 F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50-70 min was low and stable (1.066 ± 0.069) basically independent from age or gender. In patients with AD, 18 F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288 ± 0.134, moderate AD: 1.342 ± 0.191) than those of volunteers and other

  1. The Value of 18F-FDG PET/CT in Diagnosis and During Follow-up in 273 Patients with Chronic Q Fever.

    PubMed

    Kouijzer, Ilse J E; Kampschreur, Linda M; Wever, Peter C; Hoekstra, Corneline; van Kasteren, Marjo E E; de Jager-Leclercq, Monique G L; Nabuurs-Franssen, Marrigje H; Wegdam-Blans, Marjolijn C A; Ammerlaan, Heidi S M; Buijs, Jacqueline; Geus-Oei, Lioe-Fee de; Oyen, Wim J G; Bleeker-Rovers, Chantal P

    2018-01-01

    In 1%-5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18 F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18 F-FDG PET/CT scan was obtained. Clinical data and results from 18 F-FDG PET/CT at diagnosis and during follow-up were collected. 18 F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18 F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever-related mortality rate in patients with and without vascular infection based on 18 F-FDG PET/CT was 23.8% and 2.1%, respectively ( P = 0.001). When 18 F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18 F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18 F-FDG PET/CT scans resulted in treatment modification. Conclusion: 18 F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  2. 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

    PubMed

    Brito, Ana E; Santos, Allan; Sasse, André Deeke; Cabello, Cesar; Oliveira, Paulo; Mosci, Camila; Souza, Tiago; Amorim, Barbara; Lima, Mariana; Ramos, Celso D; Etchebehere, Elba

    2017-05-30

    In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448). We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

  3. Comparison of Two Site-Specifically 18F-Labeled Affibodies for PET Imaging of EGFR Positive Tumors

    DOE PAGES

    Su, Xinhui; Cheng, Kai; Jeon, Jongho; ...

    2014-06-27

    The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules 64Cu-DOTA-Z EGFR:1907 and 18F-FBEM-Z EGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with 64Cu, 18F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of 18F-FBEM-Z EGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of 18F labeled affibody probes (Al 18F-NOTA-Zmore » EGFR:1907 and 18F-CBT-Z EGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating Z EGFR:1907 with NOTA and radiolabeling with Al 18F to produce Al 18F-NOTA-Z EGFR:1907. In a second approach the prosthetic group 18F-labeled-2-cyanobenzothiazole ( 18F-CBT) was conjugated to Cys-Z EGFR:1907 to produce 18F-CBT-Z EGFR:1907. Binding affinity and specificity of Al 18F-NOTA-Z EGFR:1907 and 18F-CBT-Z EGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al 18F-NOTA-Z EGFR:1907 or 18F-CBT-Z EGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al 18F-NOTA-Z EGFR:1907 and 18F-CBT-Z EGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although 18F-CBT-Z EGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al 18F-NOTA-Z EGFR:1907 demonstrated high in vitro and in

  4. Comparison of Two Site-Specifically 18F-Labeled Affibodies for PET Imaging of EGFR Positive Tumors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Su, Xinhui; Cheng, Kai; Jeon, Jongho

    The epidermal growth factor receptor (EGFR) serves as an attractive target for cancer molecular imaging and therapy. Our previous positron emission tomography (PET) studies showed that the EGFR-targeting affibody molecules 64Cu-DOTA-Z EGFR:1907 and 18F-FBEM-Z EGFR:1907 can discriminate between high and low EGFR-expression tumors and have the potential for patient selection for EGFR-targeted therapy. Compared with 64Cu, 18F may improve imaging of EGFR-expression and is more suitable for clinical application, but the labeling reaction of 18F-FBEM-Z EGFR:1907 requires a long synthesis time. The aim of the present study is to develop a new generation of 18F labeled affibody probes (Al 18F-NOTA-Zmore » EGFR:1907 and 18F-CBT-Z EGFR:1907) and to determine whether they are suitable agents for imaging of EGFR expression. The first approach consisted of conjugating Z EGFR:1907 with NOTA and radiolabeling with Al 18F to produce Al 18F-NOTA-Z EGFR:1907. In a second approach the prosthetic group 18F-labeled-2-cyanobenzothiazole ( 18F-CBT) was conjugated to Cys-Z EGFR:1907 to produce 18F-CBT-Z EGFR:1907. Binding affinity and specificity of Al 18F-NOTA-Z EGFR:1907 and 18F-CBT-Z EGFR:1907 to EGFR were evaluated using A431 cells. Biodistribution and PET studies were conducted on mice bearing A431 xenografts after injection of Al 18F-NOTA-Z EGFR:1907 or 18F-CBT-Z EGFR:1907 with or without coinjection of unlabeled affibody proteins. The radiosyntheses of Al 18F-NOTA-Z EGFR:1907 and 18F-CBT-Z EGFR:1907 were completed successfully within 40 and 120 min with a decay-corrected yield of 15% and 41% using a 2-step, 1-pot reaction and 2-step, 2-pot reaction, respectively. Both probes bound to EGFR with low nanomolar affinity in A431 cells. Although 18F-CBT-Z EGFR:1907 showed instability in vivo, biodistribution studies revealed rapid and high tumor accumulation and quick clearance from normal tissues except the bones. In contrast, Al 18F-NOTA-Z EGFR:1907 demonstrated high in vitro and in

  5. Clinical values of (18) F-FDG PET/CT in oral cavity cancer with dental artifacts on CT or MRI.

    PubMed

    Hong, Hye Ran; Jin, Soyoung; Koo, Hyun Jung; Roh, Jong-Lyel; Kim, Jae Seung; Cho, Kyung-Ja; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2014-11-01

    2a To investigate the role of (18) F-FDG PET/CT in tumor staging, extent, and volume measurements in oral cavity squamous cell carcinoma (OSCC) patients with/without dental artifacts on CT or MRI. This study was conducted in 63 consecutive patients with OSCC who received initial workups including (18) F-FDG PET/CT and MRI. The results of the imaging modalities were compared to those of pathology, using McNemar's test and the paired t-test. Thirty-seven patients (59%) had dental or metallic artifacts obscuring primary tumors. (18) F-FDG PET/CT scanning was superior to MRI in tumor staging (weighted κ = 0.870 vs. 0.518, P = 0.004) in patients with dental artifacts. In addition, (18) F-FDG PET/CT scans were more specific than MRI in detecting sublingual gland (P = 0.014) and mouth floor (P = 0.011) involvement. In patients with dental artifacts, there was a significant discrepancy between primary tumor volume (PTV) measured by pathology and MRI (P = 0.018), but not between PTV measured from pathology and (18) F-FDG PET/CT at SUV2.5 (P = 0.245), which showed the highest intraclass correlation coefficient value (0.860). (18) F-FDG PET/CT scans provide accurate tumor staging and volume measurements in OSCC patients with CR/MRI dental artifacts, leading to improved preoperative planning. 2b CONDENSED ABSTRACT This study evaluated the clinical value of (18) F-FDG PET/CT in 63 patients with oral cavity cancers. In 37 (59%) patients with dental artifacts on CT/MRI, (18) F-FDG PET/CT showed superior results compared to MRI in tumor staging and represented the highest intraclass correlation coefficient value to tumor volume determined by pathology. © 2014 Wiley Periodicals, Inc.

  6. Italian Multicenter Study on Accuracy of 18F-FDG PET/CT in Assessing Bone Marrow Involvement in Pediatric Hodgkin Lymphoma.

    PubMed

    Cistaro, Angelina; Cassalia, Laura; Ferrara, Cinzia; Quartuccio, Natale; Evangelista, Laura; Bianchi, Maurizio; Fagioli, Franca; Bisi, Gianni; Baldari, Sergio; Zanella, Alessandro; Pillon, Marta; Zucchetta, Pietro; Burei, Marta; Sala, Alessandra; Guerra, Luca; Guglielmo, Priscilla; Burnelli, Roberta; Panareo, Stefano; Scalorbi, Federica; Rambaldi, Ilaria; Piccardo, Arnoldo; Garaventa, Alberto; Familiari, Demetrio; Fornito, Maria Concetta; Lopci, Egesta; Mascarin, Maurizio; Altini, Corinna; Ferrari, Cristina; Perillo, Teresa; Santoro, Nicola; Borsatti, Eugenio; Rubini, Giuseppe

    2018-06-01

    The present study investigated the utility of fluorine-18 ( 18 F) fluoro-2-deoxy-d-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL). A total of 224 pediatric patients with HL underwent 18 F-FDG PET/CT at staging. BMB or follow-up imaging was used as the standard of reference for the evaluation of BMI. 18 F-FDG PET/CT was negative for BMI in 193 cases. Of the 193 patients, the findings for 16 were originally reported as doubtful and later interpreted as negative for BMI, with negative findings on follow-up imaging and BMB. At BMB, 1 of the 16 patients (6.25%) had BMI. Of the 193 patients, 192 (99.48%) had negative BMB findings. Thus, the 18 F-FDG PET/CT findings were truly negative for 192 patients and falsely negative for 1 patient for BMI. 18 F-FDG PET/CT showed high diagnostic performance in the evaluation of BMI in pediatric HL. Thus, BMB should be ideally reserved for patients presenting with doubtful 18 F-FDG PET/CT findings for BMI. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. (18)F-FBPA as a tumor specific tracer of L-type amino acid transporter 1 (LAT1): PET evaluation in tumor and inflammation compared to (18)F-FDG and (11)C-methionine.

    PubMed

    Watabe, Tadashi; Hatazawa, Jun

    2015-01-01

    (18)F-FDG-PET is used worldwide for oncology patients. However, we sometimes encounter false positive cases of (18)F-FDG PET, such as moderate uptake in the inflammatory lesion, because (18)F-FDG accumulates not only in the cancer cells but also in the inflammatory cells (macrophage, granulation tissue, etc). To overcome this limitation of (18)F-FDG, we started to use (4-borono-2- [(18)F]fluoro-L-phenylalanine) (18)F-FBPA, an artificial amino acid tracer which is focusing attention as a tumor specific PET tracer. Physiological accumulation of (18)F-FBPA is limited in the kidney and urinary tract in humans, which enable preferable evaluation of uptake in the abdominal organs compared to (11)C-methionine ((11)C-MET). The purpose of this study was to evaluate (18)F-FBPA as a tumor specific tracer by in vitro cellular uptake analysis focusing on the selectivity of L-type amino acid transporter 1 (LAT1), which is specifically expressed in tumor cells, and in vivo PET analysis in rat xenograft and inflammation models compared to (18)F-FDG and (11)C-methionine. Uptake inhibition and efflux experiments were performed in HEK293-LAT1 and LAT2 cells using cold BPA, cold (18)F-FBPA, and hot (18)F-FBPA to evaluate LAT affinity and transport capacity. Position emission tomography studies were performed in rat xenograft model of C6 glioma 2 weeks after the implantation (n=9, body weight=197±10.5g) and subcutaneous inflammation model 4 days after the injection of turpentine oil (n=9, body weight=197±14.4g). Uptake on static PET images were compared among (18)F-FBPA at 60-70min post injection, (18)F-FDG at 60-70min, and (11)C-MET at 20-30min in the tumors and the inflammatory lesions by maximum standardized uptake value (SUVmax). Cellular uptake analysis showed no significant difference in inhibitory effect and efflux of LAT1 between cold (18)F-FBPA and cold BPA, suggesting the same affinity and transport capacity via LAT1. Uptake of (18)F-FBPA via LAT1 was superior to LAT2 by

  8. Diagnostic value of using 18F-FDG PET and PET/CT in immunocompetent patients with primary central nervous system lymphoma: A systematic review and meta-analysis.

    PubMed

    Zou, Yaru; Tong, Jianjing; Leng, Haiyan; Jiang, Jingwei; Pan, Meng; Chen, Zi

    2017-06-20

    18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/CT have become two of the most powerful tools for malignant lymphoma exploration, but their diagnostic role in primary central nervous system lymphoma (PCNSL) is still disputed. The purpose of our study is to identify the usefulness of 18F-FDG PET and PET/CT for detecting PCNSL. A total of 129 patients, obtained from eight eligible studies, were included for this systematic review and meta-analysis. The performance of 18F-FDG PET and PET/CT for diagnosing PCNSL were as follows: the pooled sensitivity was 0.88 (95% CI: 0.80-0.94), specificity was 0.86 (95% CI: 0.73-0.94), positive likelihood ratio (PLR) was 3.99 (95% CI: 2.31-6.90), negative likelihood ratio (NLR) was 0.11 (95% CI: 0.04-0.32), and diagnostic odds ratio (DOR) was 33.40 (95% CI: 10.40-107.3). In addition, the area under the curve (AUC) and Q index were 0.9192 and 0.8525, respectively. PubMed/MEDLINE, Embase and Cochrane Library were systematically searched for potential publications (last updated on July 16th, 2016). Reference lists of included articles were also checked. Original articles that reported data on patients who were suspected of having PCNSL were considered suitable for inclusion. The sensitivities and specificities of 18F-FDG PET and PET/CT in each study were evaluated. The Stata software and Meta-Disc software were employed in the process of data analysis. 18F-FDG PET and PET/CT showed considerable accuracy in identifying PCNSL in immunocompetent patients and could be a valuable radiological diagnostic tool for PCNSL.

  9. Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.

    PubMed

    Yamasaki, Tomoteru; Fujinaga, Masayuki; Maeda, Jun; Kawamura, Kazunori; Yui, Joji; Hatori, Akiko; Yoshida, Yuichiro; Nagai, Yuji; Tokunaga, Masaki; Higuchi, Makoto; Suhara, Tetsuya; Fukumura, Toshimitsu; Zhang, Ming-Rong

    2012-04-01

    In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5). [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

  10. (18)F-sodium fluoride PET/CT for the in vivo visualization of Mönckeberg's sclerosis in a diabetic patient.

    PubMed

    Quirce, R; Martínez-Rodríguez, I; Banzo, I; de Arcocha-Torres, M; Jiménez-Bonilla, J F; Martínez-Amador, N; Ibáñez-Bravo, S; Ramos, L; Amado, J A; Carril, J M

    2015-01-01

    Diabetes is a major frequent cause of atherosclerosis vascular disease. Arterial calcification in diabetic patients is responsible for peripheral vascular involvement. Molecular imaging using (18)F-sodium fluoride ((18)F-NaF) positron emission tomography (PET)/computed tomography (CT) has been recently proposed as a marker to study the in vivo mineralization process in the atheroma plaque. A 69-year-old man with a history of type 2 diabetes and no clinical evidence of peripheral arterial disease underwent an (18)F-NaF PET/CT scan. A linear, well-defined (18)F-NaF uptake was detected along the femoral arteries. In addition, the CT component of the PET/CT identified an unsuspected "tram-track" calcification in his femoral arteries, suggestive of medial calcification (Mönckeberg's sclerosis). In other vascular territories, focal (18)F-NaF uptake was also detected in carotid and aorta atheroma plaques. Molecular imaging with (18)F-NaF PET/CT might provide new functional information about the in vivo vascular calcification process in diabetic patients. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  11. Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging With {sup 1}H Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI, and [{sup 18}F]FDG-PET

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jansen, Jacobus F.A.; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York; Department of Radiology, Maastricht University Medical Center, Maastricht

    2012-01-01

    Purpose: To correlate proton magnetic resonance spectroscopy ({sup 1}H-MRS), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and {sup 18}F-labeled fluorodeoxyglucose positron emission tomography ([{sup 18}F]FDG PET) of nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging was evaluated for its efficacy in predicting short-term response to treatment. Methods and Materials: Metastatic neck nodes were imaged with {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET in 16 patients with newly diagnosed HNSCC, before treatment. Short-term patient radiological response was evaluated at 3 to 4 months. Correlations among {sup 1}H-MRS (choline concentrationmore » relative to water [Cho/W]), DCE-MRI (volume transfer constant [K{sup trans}]; volume fraction of the extravascular extracellular space [v{sub e}]; and redistribution rate constant [k{sub ep}]), and [{sup 18}F]FDG PET (standard uptake value [SUV] and total lesion glycolysis [TLG]) were calculated using nonparametric Spearman rank correlation. To predict short-term responses, logistic regression analysis was performed. Results: A significant positive correlation was found between Cho/W and TLG ({rho} = 0.599; p = 0.031). Cho/W correlated negatively with heterogeneity measures of standard deviation std(v{sub e}) ({rho} = -0.691; p = 0.004) and std(k{sub ep}) ({rho} = -0.704; p = 0.003). Maximum SUV (SUVmax) values correlated strongly with MRI tumor volume ({rho} = 0.643; p = 0.007). Logistic regression indicated that std(K{sup trans}) and SUVmean were significant predictors of short-term response (p < 0.07). Conclusion: Pretreatment multimodality imaging using {sup 1}H-MRS, DCE-MRI, and [{sup 18}F]FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and [{sup 18}F]FDG PET parameters were predictive of short-term response to treatment.« less

  12. 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance in Lymphoma

    PubMed Central

    Giraudo, Chiara; Raderer, Markus; Karanikas, Georgios; Weber, Michael; Kiesewetter, Barbara; Dolak, Werner; Simonitsch-Klupp, Ingrid; Mayerhoefer, Marius E.

    2016-01-01

    Objectives The aim of this study was to compare 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance (MR) (with and without diffusion-weighted imaging [DWI]) to 18F-FDG PET/computed tomography (CT), with regard to the assessment of nodal and extranodal involvement, in patients with Hodgkin lymphoma and non-Hodgkin lymphoma, without restriction to FDG-avid subytpes. Materials and Methods Patients with histologically proven lymphoma were enrolled in this prospective, institutional review board–approved study. After a single 18F-FDG injection, patients consecutively underwent 18F-FDG PET⁄CT and 18F-FDG PET/MR on the same day for staging or restaging. Three sets of images were analyzed separately: 18F-FDG PET/CT, 18F-FDG PET/MR without DWI, and 18F-FDG PET/MR with DWI. Region-based agreement and examination-based sensitivity and specificity were calculated for 18F-FDG PET/CT, 18F-FDG PET/MR without DWI, and 18F-FDG PET/MR DWI. Maximum and mean standardized uptake values (SUVmax, SUVmean) on 18F-FDG PET/CT and 18F-FDG PET/MR were compared and correlated with minimum and mean apparent diffusion coefficients (ADCmin, ADCmean). Results Thirty-four patients with a total of 40 examinations were included. Examination-based sensitivities for 18F-FDG PET/CT, 18F-FDG PET/MR, and 18F-FDG PET/MR DWI were 82.1%, 85.7%, and 100%, respectively; specificities were 100% for all 3 techniques; and accuracies were 87.5%, 90%, and 100%, respectively. 18F-FDG PET/CT was false negative in 5 of 40 examinations (all with mucosa-associated lymphoid tissue lymphoma), and 18F-FDG PET/MR (without DWI) was false negative in 4 of 40 examinations. Region-based percentages of agreement were 99% (κ, 0.95) between 18F-FDG PET/MR DWI and 18F-FDG PET/CT, 99.2% (κ, 0.96) between 18F-FDG PET/MR and 18F-FDG PET/CT, and 99.4% (κ, 0.97) between 18F-FDG PET/MR DWI and 18F-FDG PET/MR. There was a strong correlation between 18F-FDG PET/CT and 18F-FDG PET/MR for SUVmax (r = 0

  13. 5-(2-18F-fluoroethoxy)-L-tryptophan as a substrate of system L transport for tumor imaging by PET.

    PubMed

    Krämer, Stefanie D; Mu, Linjing; Müller, Adrienne; Keller, Claudia; Kuznetsova, Olga F; Schweinsberg, Christian; Franck, Dominic; Müller, Cristina; Ross, Tobias L; Schibli, Roger; Ametamey, Simon M

    2012-03-01

    Large neutral l-amino acids are substrates of system L amino acid transporters. The level of one of these, LAT1, is increased in many tumors. Aromatic l-amino acids may also be substrates of aromatic l-amino acid decarboxylase (AADC), the level of which is enhanced in endocrine tumors. Increased amino acid uptake and subsequent decarboxylation result in the intracellular accumulation of the amino acid and its decarboxylation product. (18)F- and (11)C-labeled neutral aromatic amino acids, such as l-3,4-dihydroxy-6-(18)F-fluorophenylalanine ((18)F-FDOPA) and 5-hydroxy-l-[β-(11)C]tryptophan, are thus successfully used in PET to image endocrine tumors. However, 5-hydroxy-l-[β-(11)C]tryptophan has a relatively short physical half-life (20 min). In this work, we evaluated the in vitro and in vivo characteristics of the (18)F-labeled tryptophan analog 5-(2-(18)F-fluoroethoxy)-l-tryptophan ((18)F-l-FEHTP) as a PET probe for tumor imaging. (18)F-l-FEHTP was synthesized by no-carrier-added (18)F fluorination of 5-hydroxy-l-tryptophan. In vitro cell uptake and efflux of (18)F-l-FEHTP and (18)F-FDOPA were studied with NCI-H69 endocrine small cell lung cancer cells, PC-3 pseudoendocrine prostate cancer cells, and MDA-MB-231 exocrine breast cancer cells. Small-animal PET was performed with the respective xenograft-bearing mice. Tissues were analyzed for potential metabolites. (18)F-l-FEHTP specific activity and radiochemical purity were 50-150 GBq/μmol and greater than 95%, respectively. In vitro cell uptake of (18)F-l-FEHTP was between 48% and 113% of added radioactivity per milligram of protein within 60 min at 37°C and was blocked by greater than 95% in all tested cell lines by the LAT1/2 inhibitor 2-amino-2-norboranecarboxylic acid. (18)F-FDOPA uptake ranged from 26% to 53%/mg. PET studies revealed similar xenograft-to-reference tissue ratios for (18)F-l-FEHTP and (18)F-FDOPA at 30-45 min after injection. In contrast to the (18)F-FDOPA PET results, pretreatment with the

  14. Reproducibility of functional volume and activity concentration in 18F-FDG PET/CT of liver metastases in colorectal cancer.

    PubMed

    Heijmen, Linda; de Geus-Oei, Lioe-Fee; de Wilt, Johannes H W; Visvikis, Dimitris; Hatt, Mathieu; Visser, Eric P; Bussink, Johan; Punt, Cornelis J A; Oyen, Wim J G; van Laarhoven, Hanneke W M

    2012-12-01

    Several studies showed potential for monitoring response to systemic therapy in metastatic colorectal cancer patients with (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Before (18)F-FDG PET can be implemented for response evaluation the repeatability should be known. This study was performed to assess the magnitude of the changes in standardized uptake value (SUV), volume and total lesion glycolysis (TLG) in colorectal liver metastases and validate the biological basis of (18)F-FDG PET in colorectal liver metastases. Twenty patients scheduled for liver metastasectomy underwent two (18)F-FDG PET scans within 1 week. Bland-Altman analysis was performed to assess repeatability of SUV(max), SUV(mean), volume and TLG. Tumours were delineated using an adaptive threshold method (PET(SBR)) and a semiautomatic fuzzy locally adaptive Bayesian (FLAB) delineation method. Coefficient of repeatability of SUV(max) and SUV(mean) were ∼39 and ∼31 %, respectively, independent of the delineation method used and image reconstruction parameters. However, repeatability was worse in recently treated patients. The FLAB delineation method improved the repeatability of the volume and TLG measurements compared to PET(SBR), from coefficients of repeatability of over 85 % to 45 % and 57 % for volume and TLG, respectively. Glucose transporter 1 (GLUT1) expression correlated to the SUV(mean). Vascularity (CD34 expression) and tumour hypoxia (carbonic anhydrase IX expression) did not correlate with (18)F-FDG PET parameters. In conclusion, repeatability of SUV(mean) and SUV(max) was mainly affected by preceding systemic therapy. The repeatability of tumour volume and TLG could be improved using more advanced and robust delineation approaches such as FLAB, which is recommended when (18)F-FDG PET is utilized for volume or TLG measurements. Improvement of repeatability of PET measurements, for instance by dynamic PET scanning protocols, is probably necessary to effectively

  15. Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

    PubMed

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  16. Very low-dose adult whole-body tumor imaging with F-18 FDG PET/CT

    NASA Astrophysics Data System (ADS)

    Krol, Andrzej; Naveed, Muhammad; McGrath, Mary; Lisi, Michele; Lavalley, Cathy; Feiglin, David

    2015-03-01

    The aim of this study was to evaluate if effective radiation dose due to PET component in adult whole-body tumor imaging with time-of-flight F-18 FDG PET/CT could be significantly reduced. We retrospectively analyzed data for 10 patients with the body mass index ranging from 25 to 50. We simulated F-18 FDG dose reduction to 25% of the ACR recommended dose via reconstruction of simulated shorter acquisition time per bed position scans from the acquired list data. F-18 FDG whole-body scans were reconstructed using time-of-flight OSEM algorithm and advanced system modeling. Two groups of images were obtained: group A with a standard dose of F-18 FDG and standard reconstruction parameters and group B with simulated 25% dose and modified reconstruction parameters, respectively. Three nuclear medicine physicians blinded to the simulated activity independently reviewed the images and compared diagnostic quality of images. Based on the input from the physicians, we selected optimal modified reconstruction parameters for group B. In so obtained images, all the lesions observed in the group A were visible in the group B. The tumor SUV values were different in the group A, as compared to group B, respectively. However, no significant differences were reported in the final interpretation of the images from A and B groups. In conclusion, for a small number of patients, we have demonstrated that F-18 FDG dose reduction to 25% of the ACR recommended dose, accompanied by appropriate modification of the reconstruction parameters provided adequate diagnostic quality of PET images acquired on time-of-flight PET/CT.

  17. Comparison of 4'-[methyl-(11)C]thiothymidine ((11)C-4DST) and 3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) PET/CT in human brain glioma imaging.

    PubMed

    Toyota, Yasunori; Miyake, Keisuke; Kawai, Nobuyuki; Hatakeyama, Tetsuhiro; Yamamoto, Yuka; Toyohara, Jun; Nishiyama, Yoshihiro; Tamiya, Takashi

    2015-01-01

    3'-deoxy-3'-[(18)F]fluorothymidine ((18)F-FLT) has been used to evaluate tumor malignancy and cell proliferation in human brain gliomas. However, (18)F-FLT has several limitations in clinical use. Recently, (11)C-labeled thymidine analogue, 4'-[methyl-(11)C]thiothymidine ((11)C-4DST), became available as an in vivo cell proliferation positron emission tomography (PET) tracer. The present study was conducted to evaluate the usefulness of (11)C-4DST PET in the diagnosis of human brain gliomas by comparing with the images of (18)F-FLT PET. Twenty patients with primary and recurrent brain gliomas underwent (18)F-FLT and (11)C-4DST PET scans. The uptake values in the tumors were evaluated using the maximum standardized uptake value (SUVmax), the tumor-to-normal tissue uptake (T/N) ratio, and the tumor-to-blood uptake (T/B) ratio. These values were compared among different glioma grades. Correlation between the Ki-67 labeling index and the uptake values of (11)C-4DST and (18)F-FLT in the tumor was evaluated using linear regression analysis. The relationship between the individual (18)F-FLT and (11)C-4DST uptake values in the tumors was also examined. (11)C-4DST uptake was significantly higher than that of (18)F-FLT in the normal brain. The uptake values of (11)C-4DST in the tumor were similar to those of (18)F-FLT resulting in better visualization with (18)F-FLT. No significant differences in the uptake values of (18)F-FLT and (11)C-4DST were noted among different glioma grades. Linear regression analysis showed a significant correlation between the Ki-67 labeling index and the T/N ratio of (11)C-4DST (r = 0.50, P < 0.05) and (18)F-FLT (r = 0.50, P < 0.05). Significant correlations were also found between the Ki-67 labeling index and the T/B ratio of (11)C-4DST (r = 0.52, P < 0.05) and (18)F-FLT (r = 0.55, P < 0.05). A highly significant correlation was observed between the individual T/N ratio of (11)C-4DST and (18)F-FLT in the tumor (r

  18. 18F-FDG PET/CT Can Predict Development of Thyroiditis due to Immunotherapy for Lung Cancer.

    PubMed

    Eshghi, Naghmehossadat; Garland, Linda; Nia, Emily Saghar; Betancourt, Robert; Krupinski, Elizabeth; Kuo, Phillip H

    2018-03-29

    Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased 18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if 18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with 18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver and spleen. Patients obtained monthly thyroid testing. PET/CT parameters were analyzed by unpaired t-test for differences between two groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab received was also tested. Results: Six of eighteen patients developed hypothyroidism. T-test comparing the two groups (patients who developed hypothyroidism and those who did not) demonstrated significant differences in SUVmean ( P = 0.04), SUV max ( P = 0.04) and TLG ( P = 0.02) of the thyroid gland. Two of four patients who developed thyroiditis and had increased 18 F-FDG uptake in the thyroid gland, had normal TSH at time of follow-up 18 F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) compared to patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver or spleen. Conclusion: 18 F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy. Copyright © 2018 by the Society of Nuclear

  19. Biodistribution and Stability Studies of [18F]Fluoroethylrhodamine B, a Potential PET Myocardial Perfusion Agent

    PubMed Central

    Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederick H; Treves, S. Ted; Packard, Alan B.

    2010-01-01

    Introduction Fluorine-18-labeled rhodamine B was developed as a potential PET tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was, therefore, undertaken to further evaluate this hypothesis. Methods [18F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 °C in human, rat and mouse serum and in PBS. Samples were removed periodically and assayed by HPLC. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results In vitro stability studies demonstrated that [18F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but <30% intact in mouse serum. The microPET imaging and biodistribution studies in rats confirmed this result showing high and persistent tracer accumulation in the myocardium compared with the absence of uptake by the myocardium in mice thereby validating our original hypothesis that 18F-labeled rhodamines should accumulate in the heart. Conclusions [18F]Fluoroethyl rhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion. PMID:20346876

  20. Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis.

    PubMed

    Solnes, Lilja B; Jones, Krystyna M; Rowe, Steven P; Pattanayak, Puskar; Nalluri, Abhinav; Venkatesan, Arun; Probasco, John C; Javadi, Mehrbod S

    2017-08-01

    Diagnosis of autoimmune encephalitis presents some challenges in the clinical setting because of varied clinical presentations and delay in obtaining antibody panel results. We examined the role of neuroimaging in the setting of autoimmune encephalitides, comparing the utility of 18 F-FDG PET/CT versus conventional brain imaging with MRI. Methods: A retrospective study was performed assessing the positivity rate of MRI versus 18 F-FDG PET/CT during the initial workup of 23 patients proven to have antibody-positive autoimmune encephalitis. 18 F-FDG PET/CT studies were analyzed both qualitatively and semiquantitatively. Areas of cortical lobar hypo (hyper)-metabolism in the cerebrum that were 2 SDx from the mean were recorded as abnormal. Results: On visual inspection, all patients were identified as having an abnormal pattern of 18 F-FDG uptake. In semiquantitative analysis, at least 1 region of interest with metabolic change was identified in 22 of 23 (95.6%) patients using a discriminating z score of 2. Overall, 18 F-FDG PET/CT was more often abnormal during the diagnostic period than MRI (10/23, 43% of patients). The predominant finding on brain 18 F-FDG PET/CT imaging was lobar hypometabolism, being observed in 21 of 23 (91.3%) patients. Hypometabolism was most commonly observed in the parietal lobe followed by the occipital lobe. An entire subset of antibody-positive patients, anti- N -methyl-d-aspartate receptor (5 patients), had normal MRI results and abnormal 18 F-FDG PET/CT findings whereas the other subsets demonstrated a greater heterogeneity. Conclusion: Brain 18 F-FDG PET/CT may play a significant role in the initial evaluation of patients with clinically suspected antibody-mediated autoimmune encephalitis. Given that it is more often abnormal when compared with MRI in the acute setting, this molecular imaging technique may be better positioned as an early biomarker of disease so that treatment may be initiated earlier, resulting in improved patient

  1. Metabolically active tumour volume segmentation from dynamic [(18)F]FLT PET studies in non-small cell lung cancer.

    PubMed

    Hoyng, Lieke L; Frings, Virginie; Hoekstra, Otto S; Kenny, Laura M; Aboagye, Eric O; Boellaard, Ronald

    2015-01-01

    Positron emission tomography (PET) with (18)F-3'-deoxy-3'-fluorothymidine ([(18)F]FLT) can be used to assess tumour proliferation. A kinetic-filtering (KF) classification algorithm has been suggested for segmentation of tumours in dynamic [(18)F]FLT PET data. The aim of the present study was to evaluate KF segmentation and its test-retest performance in [(18)F]FLT PET in non-small cell lung cancer (NSCLC) patients. Nine NSCLC patients underwent two 60-min dynamic [(18)F]FLT PET scans within 7 days prior to treatment. Dynamic scans were reconstructed with filtered back projection (FBP) as well as with ordered subsets expectation maximisation (OSEM). Twenty-eight lesions were identified by an experienced physician. Segmentation was performed using KF applied to the dynamic data set and a source-to-background corrected 50% threshold (A50%) was applied to the sum image of the last three frames (45- to 60-min p.i.). Furthermore, several adaptations of KF were tested. Both for KF and A50% test-retest (TRT) variability of metabolically active tumour volume and standard uptake value (SUV) were evaluated. KF performed better on OSEM- than on FBP-reconstructed PET images. The original KF implementation segmented 15 out of 28 lesions, whereas A50% segmented each lesion. Adapted KF versions, however, were able to segment 26 out of 28 lesions. In the best performing adapted versions, metabolically active tumour volume and SUV TRT variability was similar to those of A50%. KF misclassified certain tumour areas as vertebrae or liver tissue, which was shown to be related to heterogeneous [(18)F]FLT uptake areas within the tumour. For [(18)F]FLT PET studies in NSCLC patients, KF and A50% show comparable tumour volume segmentation performance. The KF method needs, however, a site-specific optimisation. The A50% is therefore a good alternative for tumour segmentation in NSCLC [(18)F]FLT PET studies in multicentre studies. Yet, it was observed that KF has the potential to subsegment

  2. Role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in evaluating patients with pheochromocytoma.

    PubMed

    Bandopadhyaya, G P; Kumar, Abhishek; Kumari, Jyotsana

    2015-01-01

    The aim of this retrospective study was to evaluate role of (18)F-DOPA PET/CT and (131)I-MIBG planar scintigraphy in patients with pheochromocytoma. The patients with diagnosis of pheochromocytoma based on radiological and biochemical markers were retrospectively selected for the study. These patients had undergone both (131)I-MIBG scintigraphy and (18)F-DOPA PET/CT. The imaging findings were compared to patient histopathology reports, biochemical markers and clinical follow up whenever available to establish the diagnosis. (131)I-MIBG showed a sensitivity of 68% and specificity of 100%. (18)F-DOPA PET/CT showed a sensitivity of 82% and specificity of 100%. (18)F-DOPA was better at localizing and finding more no of lesions as compared to (131)I-MIBG scintigraphy. (18)F-DOPA also is a better study in evaluation of paragangliomas. (18)F-DOPA PET/CT seems to be a better modality in comparison to (131)I-MIBG scintigraphy in the evaluation of pheochromocytoma/paraganglioma. At this point both these tracers seem to have mutually additive role in these patients and essential investigations with diagnosis and follow-up of this disease.

  3. Functional imaging in differentiating bronchial masses: an initial experience with a combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan.

    PubMed

    Kumar, Arvind; Jindal, Tarun; Dutta, Roman; Kumar, Rakesh

    2009-10-01

    To evaluate the role of combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in differentiating bronchial tumors observed in contrast enhanced computed tomography scan of chest. Prospective observational study. Place of study: All India Institute of Medical Sciences, New Delhi, India. 7 patients with bronchial mass detected in computed tomography scan of the chest were included in this study. All patients underwent (18)F-FDG PET-CT scan, (68)Ga DOTA-TOC PET-CT scan and fiberoptic bronchoscope guided biopsy followed by definitive surgical excision. The results of functional imaging studies were analyzed and the results are correlated with the final histopathology of the tumor. Histopathological examination of 7 bronchial masses revealed carcinoid tumors (2 typical, 1 atypical), inflammatory myofibroblastic tumor (1), mucoepidermoid carcinoma (1), hamartoma (1), and synovial cell sarcoma (1). The typical carcinoids had mild (18)F-FDG uptake and high (68)Ga DOTA-TOC uptake. Atypical carcinoid had moderate uptake of (18)F-FDG and high (68)Ga DOTA-TOC uptake. Inflammatory myofibroblastic tumor showed high uptake of (18)F-FDG and no uptake of (68)Ga DOTA-TOC. Mucoepidermoid carcinoma showed mild (18)F-FDG uptake and no (68)Ga DOTA-TOC uptake. Hamartoma showed no uptake on either scans. Synovial cell sarcoma showed moderate (18)F-FDG uptake and mild focal (68)Ga DOTA-TOC uptake. This initial experience with the combined use of (18)F-FDG and (68)Ga DOTA-TOC PET-CT scan reveals different uptake patterns in various bronchial tumors. Bronchoscopic biopsy will continue to be the gold standard; however, the interesting observations made in this study merits further evaluation of the utility of the combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in larger number of patients with bronchial masses.

  4. [Diagnostic value of (18)F-FDG PET/CT for solitary nodular-type bronchoalveolar carcinoma].

    PubMed

    Liu, Weikun; Li, Xiangdong; Quan, Jiangtao; Ouyang, Xi; Zheng, Hui

    2013-01-01

    To assess the value of (18)F-FDG PET/CT in the diagnosis of solitary nodular-type bronchoalveolar carcinoma (BAC). The clinical and radiographic data were analyzed retrospectively in 30 patients with pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT examinations between August, 2005 and December, 2006. The morphological and radioactive findings of the lesions were reviewed, and the maximum standard uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and HRCT were analyzed. The (18)F-FDG SUV was markedly lower in BAC than in other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30 cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT showed that BAC located often in the superior lobes of the bilateral lungs, mostly below the pleura in the surrounding lung field; the lesions were patchy or nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15 cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was 36.67%, 93.33%, and 93.33%, respectively. The SUVmax of BAC provides only limited value for defining the nature of the lesions, but can serve as a general reference for assessing the disease activity. PET/CT, which allows both functional and imaging assessment, can be a valuable modality to reduce the misdiagnosis rate of BAC.

  5. [Diagnostic value of (18)F-FDG PET/CT for solitary nodular-type bronchoalveolar carcinoma].

    PubMed

    Liu, Wei-Kun; Li, Xiang-Dong; Quan, Jiang-Tao; Ouyang, Xi; Zheng, Hui

    2015-01-01

    To assess the value of (18)F-FDG PET/CT in the diagnosis of solitary nodular-type bronchoalveolar carcinoma (BAC). The clinical and radiographic data were analyzed retrospectively in 30 patients with pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT examinations between August, 2005 and December, 2006. The morphological and radioactive findings of the lesions were reviewed, and the maximum standard uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and HRCT were analyzed. The (18)F-FDG SUV was markedly lower in BAC than in other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30 cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT showed that BAC located often in the superior lobes of the bilateral lungs, mostly below the pleura in the surrounding lung field; the lesions were patchy or nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15 cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was 36.67%, 93.33%, and 93.33%, respectively. The SUVmax of BAC provides only limited value for defining the nature of the lesions, but can serve as a general reference for assessing the disease activity. PET/CT, which allows both functional and imaging assessment, can be a valuable modality to reduce the misdiagnosis rate of BAC.

  6. WE-H-207A-04: Impact of Lesion Location On the Repeatability of 18F-NaF PET/CT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, C; Perk, T; Harmon, S

    Purpose: Quantifying the repeatability of imaging biomarkers is critical for assessing therapeutic response. While {sup 18}F-NaF PET/CT has shown to be a repeatable imaging method, research has not shown which factors may influence its repeatability. The purpose of this study was to evaluate whether the location of the lesion impacts the repeatability of quantitative {sup 18}F-NaF PET-derived SUV metrics. Methods: Metastatic castrate-resistant prostate cancer patients with multiple bone lesions received whole-body test-retest NaF PET/CT scans. Malignant bone lesions of PET-defined volume greater than 1.5 cm{sup 3} were identified by a nuclear medicine physician and automatically delineated using a SUV>15 threshold.more » The maximum (SUVmax), average (SUVmean), and total (SUVtotal) SUV were extracted from each lesion. Atlas-based segmentation was used to divide each patient skeleton into 25 skeletal regions. Test-retest repeatability of each SUV metric was assessed with coefficient of variation (CV). Results: A total of 265 malignant bone lesions from 18 patients were identified by nuclear medicine physician. The largest proportion of bone lesions were localized to the spine (41%), with 41% of those lesions localized to the thoracic spine. One-way ANOVA showed that measurement differences differed significantly for all three metrics across locations (p<0.01 for each metrics). Overall, CV was smallest for SUVmean at 5.3%, followed by SUVmax at 11.5% and SUVtotal at 20.4%. Lesions in the pubis were consistently the most repeatable (CV(SUVmax)= 5.6%, CV(SUVmean)= 0.6%, CV(SUVtotal)= 2.9%). According to SUVmean, repeatability was poorest in the cervical spine (CV = 6.2%), whereas according to SUVmax and SUVtotal, repeatability was poorest in the ribs (CV(SUVmax)= 15.0%, CV(SUVtotal)= 29.8%). Conclusion: Location of the lesion affects the repeatability of {sup 18}F-NaF PET/CT, with the ribs and cervical spine having the lowest repeatability and the pubis having the

  7. Human biodistribution and dosimetry of [18F]nifene, an α4β2* nicotinic acetylcholine receptor PET tracer.

    PubMed

    Betthauser, Tobey J; Hillmer, Ansel T; Lao, Patrick J; Ehlerding, Emily; Mukherjee, Jogeshwar; Stone, Charles K; Christian, Bradley T

    2017-12-01

    The α4β2* nicotinic acetylcholine receptor (nAChR) system is implicated in many neuropsychiatric pathologies. [ 18 F]Nifene is a positron emission tomography (PET) ligand that has shown promise for in vivo imaging of the α4β2* nAChR system in preclinical models and humans. This work establishes the radiation burden associated with [ 18 F]nifene PET scans in humans. Four human subjects (2M, 2F) underwent whole-body PET/CT scans to determine the human biodistribution of [ 18 F]nifene. Source organs were identified and time-activity-curves (TACs) were extracted from the PET time-series. Dose estimates were calculated for each subject using OLINDA/EXM v1.1. [ 18 F]Nifene was well tolerated by all subjects with no adverse events reported. The mean whole-body effective dose was 28.4±3.8 mSv/MBq without bladder voiding, and 22.6±1.9 mSv/MBq with hourly micturition. The urinary bladder radiation dose limited the maximum injected dose for a single scan to 278 MBq without urinary bladder voiding, and 519 MBq with hourly voiding. [ 18 F]Nifene is a safe PET radioligand for imaging the α4β2* nAChR system in humans. This works presents human internal dosimetry for [ 18 F]nifene in humans for the first time. These results facilitate safe development of future [ 18 F]nifene studies to image the α4β2* nAChR system in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Synthesis and preliminary evaluation of 18-(18)F-fluoro-4-thia-oleate as a PET probe of fatty acid oxidation.

    PubMed

    DeGrado, Timothy R; Bhattacharyya, Falguni; Pandey, Mukesh K; Belanger, Anthony P; Wang, Shuyan

    2010-08-01

    Fatty acid oxidation (FAO) is a major energy-providing process with important implications in cardiovascular, oncologic, neurologic, and metabolic diseases. A novel 4-thia oleate analog, 18-(18)F-fluoro-4-thia-oleate ((18)F-FTO), was evaluated in relationship to the previously developed palmitate analog 16-(18)F-fluoro-4-thia-palmitate ((18)F-FTP) as an FAO probe. (18)F-FTO was synthesized from a corresponding bromoester. Biodistribution and metabolite analysis studies were performed in rats. Preliminary small-animal PET studies were performed with (18)F-FTO and (18)F-FTP in rats. A practical synthesis of (18)F-FTO was developed, providing a radiotracer of high radiochemical purity (>99%). In fasted rats, myocardial uptake of (18)F-FTO (0.70 +/- 0.30% dose kg [body mass]/g [tissue mass]) was similar to that of (18)F-FTP at 30 min after injection. At 2 h, myocardial uptake of (18)F-FTO was maintained, whereas (18)F-FTP uptake in the heart was 82% reduced. Similar to (18)F-FTP, (18)F-FTO uptake by the heart was approximately 80% reduced at 30 min by pretreatment of rats with the CPT-I inhibitor etomoxir. Folch-type extraction analyses showed 70-90% protein-bound fractions in the heart, liver, and skeletal muscle, consistent with efficient trafficking of (18)F-FTO to the mitochondrion with subsequent metabolism to protein-bound species. Preliminary small-animal PET studies showed rapid blood clearance and avid extraction of (18)F-FTO and of (18)F-FTP into the heart and liver. Images of (18)F-FTO accumulation in the rat myocardium were clearly superior to those of (18)F-FTP. (18)F-FTO is shown to be a promising metabolically trapped FAO probe that warrants further evaluation.

  9. Does Antibiotic Treatment Affect the Diagnostic Accuracy of 18F-FDG PET/CT Studies in Patients with Suspected Infectious Processes?

    PubMed

    Kagna, Olga; Kurash, Marina; Ghanem-Zoubi, Nesrin; Keidar, Zohar; Israel, Ora

    2017-11-01

    18 F-FDG PET/CT plays a significant role in the assessment of various infectious processes. Patients with suspected or known sites of infection are often referred for 18 F-FDG imaging while already receiving antibiotic treatment. The current study assessed whether antibiotic therapy affected the detectability rate of infectious processes by 18 F-FDG PET/CT. Methods: A 5-y retrospective study of all adult patients who underwent 18 F-FDG PET/CT in search of a focal source of infection was performed. The presence, duration, and appropriateness of antibiotic treatment before 18 F-FDG imaging were recorded. Diagnosis of an infectious process was based on microbiologic or pathologic data as well as on clinical and radiologic follow-up. Results: Two hundred seventeen patients underwent 243 PET/CT studies in search of a focal source of infection and were included in the study. Sixty-seven studies were excluded from further analysis because of a final noninfectious etiology or lack of further follow-up or details regarding the antibiotic treatment. The final study population included 176 18 F-FDG PET/CT studies in 153 patients (107 men, 46 women; age range, 18-86 y). One hundred nineteen studies (68%) were performed in patients receiving antibiotic therapy for a range of 1-73 d. A diagnosis of infection was made in 107 true-positive cases (61%), including 63 studies (59%) in patients receiving appropriate antibiotic therapy started before the performance of the 18 F-FDG PET/CT study. There were 52 true-negative (29%) and 17 false-positive (10%) 18 F-FDG PET/CT studies. No false-negative results were found. Conclusion: 18 F-FDG PET/CT correctly identified foci of increased uptake compatible with infection in most patients, including all patients receiving appropriate antimicrobial therapy, with no false-negative cases. On the basis of the current study results, the administration of antibiotics appears to have no clinically significant impact on the diagnostic accuracy of 18

  10. WE-H-207A-05: Spatial Co-Localization of F-18 NaF Vs. F-18 FDG Defined Disease Volumes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ferjancic, P; Harmon, S; Jeraj, R

    Purpose: Both [F-18]NaF and [F-18]FDG show promise for quantitative PET/CT assessment in metastatic prostate cancer to bone. Broad agreement between the tracers has been shown but voxel-wise correspondence has not been explored in depth. This study evaluates the spatial co-localization of [F-18]NaF PET and [F-18]FDG PET in bone lesions. Methods: Seventy-three lesion contours were identified in six patients receiving dynamic NaF PET/CT and FDG PET/CT scans two hours apart using identical fields-of-view. Tracer uptake (SUV) reflecting 60 minutes post-injection was modeled from kinetic parameters. Lesions were segmented by a physician separately on NaF PET and FDG PET. PET images weremore » rigidly aligned using skeletal references on CT images. Lesion size, degree of overlap, voxel-wise tracer uptake values (SUV), and CT density distributions were compared using Dice coefficient, Positive Predictive Value (PPV), and Spearman rank correlation tests. Results: Across all patients, 42 lesions were identified on NaF PET (median 1.4 cm{sup 3}, range <1–204 cm{sup 3}) compared to 31 using FDG PET (median 1.8 cm{sup 3}, range <1–244 cm{sup 3}). Spatial cooccurrence was found in 25 lesion pairs. Lesions on NaF PET had PPV of 0.91 and on FDG a PPV of 0.65. Overall, NaF-defined lesions were 47% (±24%) larger by volume with moderate overlap to FDG, resulting in mean Dice coefficient of 34% (±22%). In areas of overlap, voxel-wise correlation of NaF and FDG SUV was moderate (ρ=0.56). Expanding to regions of non-spatial overlap, voxels contained in FDG-only contours were almost exclusively low HU (median 118), compared to dense regions of NaF-only voxels (median 250). In sclerotic sub-volumes (HU > 300) NaF-defined contours encompassed 83% of total FDG volume. Conclusion: Moderate voxel-wise correlation of FDG and NaF PET/CT uptake was observed. Spatial discrepancies in FDG and NaF PET/CT imaging of boney metastases could be influenced by poor sensitivity of FDG PET/CT in

  11. In vivo spatial correlation between (18)F-BPA and (18)F-FDG uptakes in head and neck cancer.

    PubMed

    Kobayashi, Kazuma; Kurihara, Hiroaki; Watanabe, Yoshiaki; Murakami, Naoya; Inaba, Koji; Nakamura, Satoshi; Wakita, Akihisa; Okamoto, Hiroyuki; Umezawa, Rei; Takahashi, Kana; Igaki, Hiroshi; Ito, Yoshinori; Yoshimoto, Seiichi; Shigematsu, Naoyuki; Itami, Jun

    2016-09-01

    Borono-2-(18)F-fluoro-phenylalanine ((18)F-BPA) has been used to estimate the therapeutic effects of boron neutron capture therapy (BNCT), while (18)F-fluorodeoxyglucose ((18)F-FDG) is the most commonly used positron emission tomography (PET) radiopharmaceutical in a routine clinical use. The aim of the present study was to evaluate spatial correlation between (18)F-BPA and (18)F-FDG uptakes using a deformable image registration-based technique. Ten patients with head and neck cancer were recruited from January 2014 to December 2014. All patients underwent whole-body (18)F-BPA PET/computed tomography (CT) and (18)F-FDG PET/CT within a 2-week period. For each patient, (18)F-BPA PET/CT and (18)F-FDG PET/CT images were aligned based on a deformable image registration framework. The voxel-by-voxel spatial correlation of standardized uptake value (SUV) within the tumor was analyzed. Our image processing framework achieved accurate and validated registration results for each PET/CT image. In 9/10 patients, the spatial distribution of SUVs between (18)F-BPA and (18)F-FDG showed a significant, positive correlation in the tumor volume. Deformable image registration-based voxel-wise analysis demonstrated a spatial correlation between (18)F-BPA and (18)F-FDG uptakes in the head and neck cancer. A tumor sub-volume with a high (18)F-FDG uptake may predict high accumulation of (18)F-BPA. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 18F-FDG PET/CT in Detecting Metastatic Infection in Children.

    PubMed

    Kouijzer, Ilse J E; Blokhuis, Gijsbert J; Draaisma, Jos M T; Oyen, Wim J G; de Geus-Oei, Lioe-Fee; Bleeker-Rovers, Chantal P

    2016-04-01

    Metastatic infection is a severe complication of bacteremia with high morbidity and mortality. The aim of this study was to investigate the diagnostic value of 18F-FDG PET combined with CT (FDG PET/CT) in children suspected of having metastatic infection. The results of FDG PET/CT scans performed in children because of suspected metastatic infection from September 2003 to June 2013 were analyzed retrospectively. The results were compared with the final clinical diagnosis. FDG PET/CT was performed in 13 children with suspected metastatic infection. Of the total number of FDG PET/CT scans, 38% were clinically helpful. Positive predictive value of FDG PET/CT was 71%, and negative predictive value was 100%. FDG PET/CT appears to be a valuable diagnostic technique in children with suspected metastatic infection. Prospective studies of FDG PET/CT as part of a structured diagnostic protocol are needed to assess the exact additional diagnostic value.

  13. Application of Palladium-Mediated 18F-Fluorination to PET Radiotracer Development: Overcoming Hurdles to Translation

    PubMed Central

    Kamlet, Adam S.; Neumann, Constanze N.; Lee, Eunsung; Carlin, Stephen M.; Moseley, Christian K.; Stephenson, Nickeisha; Hooker, Jacob M.; Ritter, Tobias

    2013-01-01

    New chemistry methods for the synthesis of radiolabeled small molecules have the potential to impact clinical positron emission tomography (PET) imaging, if they can be successfully translated. However, progression of modern reactions from the stage of synthetic chemistry development to the preparation of radiotracer doses ready for use in human PET imaging is challenging and rare. Here we describe the process of and the successful translation of a modern palladium-mediated fluorination reaction to non-human primate (NHP) baboon PET imaging–an important milestone on the path to human PET imaging. The method, which transforms [18F]fluoride into an electrophilic fluorination reagent, provides access to aryl–18F bonds that would be challenging to synthesize via conventional radiochemistry methods. PMID:23554994

  14. Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.

    PubMed

    Takkinen, Jatta S; López-Picón, Francisco R; Al Majidi, Rana; Eskola, Olli; Krzyczmonik, Anna; Keller, Thomas; Löyttyniemi, Eliisa; Solin, Olof; Rinne, Juha O; Haaparanta-Solin, Merja

    2017-08-01

    Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo 18 F-FDG and 18 F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with 18 F-FDG and 18 F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the 18 F-FDG SUVs were lower and the 18 F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo 18 F-DPA-714 studies but not the 18 F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.

  15. The value of [11C]-acetate PET and [18F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab.

    PubMed

    Li, Shuren; Peck-Radosavljevic, Markus; Ubl, Philipp; Wadsak, Wolfgang; Mitterhauser, Markus; Rainer, Eva; Pinter, Matthias; Wang, Hao; Nanoff, Christian; Kaczirek, Klaus; Haug, Alexander; Hacker, Marcus

    2017-09-01

    This prospective study was to investigate the value of [ 11 C]-acetate PET and [ 18 F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab). Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [ 11 C]-acetate PET and [ 18 F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively. The patient-related sensitivity of [ 11 C]-acetate PET, [ 18 F]-FDG PET, and combined [ 11 C]-acetate and [ 18 F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [ 11 C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC. Our study suggests that combining [ 18 F]-FDG with [ 11 C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

  16. [18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging.

    PubMed

    Lemoine, Laëtitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Le Bars, Didier; Newman-Tancredi, Adrian; Zimmer, Luc

    2010-03-01

    The serotonin-1A (5-HT(1A)) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT(1A) receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT(1A) receptors. Since all clinical PET 5-HT(1A) radiopharmaceuticals are antagonists, it is of great interest to develop a( 18)F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT(1A) receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT(1A) receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [(18)F]MPPF, a validated 5-HT(1A) antagonist radiopharmaceutical. The chemical and radiochemical purities of [(18)F]F15599 were >98%. In vitro [(18)F]F15599 binding was consistent with the known 5-HT(1A) receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [(18)F]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [(18)F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT(1A) antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain

  17. Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18F]FDG PET/CT study in mice

    PubMed Central

    Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

    2013-01-01

    Objective Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [18F]fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET)/ computed tomography (CT) in mice. Methods A β3-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine) were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [18F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [18F]FDG PET images. CL 316243 increased the total [18F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [18F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [18F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [18F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [18F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT hounsfiled unit (HU) (R2=0.55, p<0.001) and

  18. Effectiveness of Breast MRI and (18)F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma.

    PubMed

    Jung, Na Young; Kim, Sung Hoon; Kim, Sung Hun; Seo, Ye Young; Oh, Jin Kyoung; Choi, Hyun Su; You, Won Jong

    2015-03-01

    We evaluated the utility of magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC). The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and (18)F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups. Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on (18)F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of (18)F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of (18)F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with (18)F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or (18)F-FDG PET/CT for ILC versus IDC. The MRI and (18)F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although (18)F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of

  19. Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging.

    PubMed

    Declercq, Lieven; Rombouts, Frederik; Koole, Michel; Fierens, Katleen; Mariën, Jonas; Langlois, Xavier; Andrés, José Ignacio; Schmidt, Mark; Macdonald, Gregor; Moechars, Diederik; Vanduffel, Wim; Tousseyn, Thomas; Vandenberghe, Rik; Van Laere, Koen; Verbruggen, Alfons; Bormans, Guy

    2017-06-01

    In this study, we have synthesized and evaluated 18 F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18 F-AV1451 ( 18 F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18 F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time-activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18 F

  20. Quantification of Dynamic [18F]FDG Pet Studies in Acute Lung Injury.

    PubMed

    Grecchi, Elisabetta; Veronese, Mattia; Moresco, Rosa Maria; Bellani, Giacomo; Pesenti, Antonio; Messa, Cristina; Bertoldo, Alessandra

    2016-02-01

    This work aims to investigate lung glucose metabolism using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging in acute lung injury (ALI) patients. Eleven ALI patients and five healthy controls underwent a dynamic [(18)F]FDG PET/X-ray computed tomography (CT) scan. The standardized uptake values (SUV) and three different methods for the quantification of glucose metabolism (i.e., ratio, Patlak, and spectral analysis iterative filter, SAIF) were applied both at the region and the voxel levels. SUV reported a lower correlation than the ratio with the net tracer uptake. Patlak and SAIF analyses did not show any significant spatial or quantitative (R(2) > 0.80) difference. The additional information provided by SAIF showed that in lung inflammation, elevated tracer uptake is coupled with abnormal tracer exchanges within and between lung tissue compartments. Full kinetic modeling provides a multi-parametric description of glucose metabolism in the lungs. This allows characterizing the spatial distribution of lung inflammation as well as returning the functional state of the tissues.

  1. Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

    PubMed

    Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

    2013-06-01

    In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study

  2. 18F-FDG PET of the hands with a dedicated high-resolution PEM system (arthro-PET): correlation with PET/CT, radiography and clinical parameters.

    PubMed

    Mhlanga, Joyce C; Carrino, John A; Lodge, Martin; Wang, Hao; Wahl, Richard L

    2014-12-01

    The aim of this study was to prospectively determine the feasibility and compare the novel use of a positron emission mammography (PEM) scanner with standard PET/CT for evaluating hand osteoarthritis (OA) with (18)F-FDG. Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study in which 14 adults referred for oncological (18)F-FDG PET/CT underwent dedicated hand PET/CT followed by arthro-PET using the PEM device. Hand radiographs were obtained and scored for the presence and severity of OA. Summed qualitative and quantitative joint glycolytic scores for each modality were compared with the findings on plain radiography and clinical features. Eight patients with clinical and/or radiographic evidence of OA comprised the OA group (mean age 73 ± 7.7 years). Six patients served as the control group (53.7 ± 9.3 years). Arthro-PET quantitative and qualitative joint glycolytic scores were highly correlated with PET/CT findings in the OA patients (r = 0.86. p = 0.007; r = 0.94, p = 0.001). Qualitative arthro-PET and PET/CT joint scores were significantly higher in the OA patients than in controls (38.7 ± 6.6 vs. 32.2 ± 0.4, p = 0.02; 37.5 ± 5.4 vs. 32.2 ± 0.4, p = 0.03, respectively). Quantitative arthro-PET and PET/CT maximum SUV-lean joint scores were higher in the OA patients, although they did not reach statistical significance (20.8 ± 4.2 vs. 18 ± 1.8, p = 0.13; 22.8 ± 5.38 vs. 20.1 ± 1.54, p = 0.21). By definition, OA patients had higher radiographic joint scores than controls (30.9 ± 31.3 vs. 0, p = 0.03). Hand imaging using a small field of view PEM system (arthro-PET) with FDG is feasible, performing comparably to PET/CT in assessing metabolic joint activity. Arthro-PET and PET/CT showed higher joint FDG uptake in OA. Further exploration of arthro-PET in arthritis management is warranted.

  3. Complementary roles of tumour specific PET tracer ¹⁸F-FAMT to ¹⁸F-FDG PET/CT for the assessment of bone metastasis.

    PubMed

    Morita, Motoho; Higuchi, Tetsuya; Achmad, Arifudin; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito

    2013-10-01

    The usefulness of (18)F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [(18)F]-3-fluoro-alpha-methyl tyrosine ((18)F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of (18)F-FAMT PET/CT to complement (18)F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both (18)F-FDG and (18)F-FAMT PET/CT within 1 month of each other. (18)F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the (18)F-FAMT in the corresponding lesions were evaluated. A total of 72 (18)F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. (18)F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of (18)F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher (18)F-FAMT uptake than those of adenocarcinoma. No significant difference in (18)F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of (18)F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that (18)F-FAMT uptake was confirmed by (18)F-FDG uptake suggests that (18)F-FAMT PET/CT has the potential to complement (18)F-FDG PET/CT for the detection of bone metastases.

  4. Role of (18)F-FDG PET/CT in the evaluation of response to antibiotic therapy in patients affected by infectious spondylodiscitis.

    PubMed

    Niccoli Asabella, Artor; Iuele, Francesca; Simone, Francesco; Fanelli, Margherita; Lavelli, Valentina; Ferrari, Cristina; Di Palo, Alessandra; Notaristefano, Antonio; Merenda, Nunzio Clemente; Rubini, Giuseppe

    2015-01-01

    Spondylodiscitis is characterized by infection involving the intervertebral disc and adjacent vertebrae. It can occur anywhere in the vertebral column but more commonly involves lumbar spine. Our aim was to evaluate the usefulness of (18)F-FDG PET/CT to detect the early response to antibiotic therapy in patients affected by infectious spondylodiscitis and to compare the role of (18)F-FDG PET/CT and MRI in post-treatment evaluation. 15 patients (12M, 3F), with mean age 65±13 years old, with typical clinical symptoms of Infectious Spondylodiscitis (pain, fever and increase of inflammatory indexes) and confirmed by blood culture or vertebral biopsy underwent within three day-interval a (18)F-FDG PET/CT and Magnetic Resonance (MR) at "baseline" and after antibiotic therapy. Semiquantitative parameters at (18)F-FDG PET/CT "baseline" SUVmax1, MTV1 and TLG1 and after therapy SUVmax2, MTV2 and TLG2 of involved vertebrae were calculated. Follow-up period of at least three months was available for all patients. T-student test for paired groups was performed to compare baseline and after therapy (18)F-FDG PET/CT semiquantitative parameters. According to (18)F-FDG PET/CT parameters all patients showed a response to antibiotic therapy. All patients were positive at "baseline" MRI of the spine, while at follow-up, 7/15 patients showed MR signs of infection and were considered "positive" and 8/15 showed resolution of infectious condition and, therefore they were considered "negative". A statistical significant difference between (18)F-FDG PET/CT "baseline" and after antibiotic therapy was found for all semiquantitative parameters: SUVmax (t=5.8, P=0.01); MTV (t=5.17, P=0.001); TLG (t=5,26, P=0,001). The comparison between the "baseline" and "after treatment" (18)F-FDG semiquantitative parameters showed a significant reduction of all parameters. This reduction was relevant also in patients with positive post-treatment MRI. This can be probably related to the tissue remodeling in

  5. 18F-EF5 PET-based Imageable Hypoxia Predicts Local Recurrence in Tumors Treated With Highly Conformal Radiation Therapy.

    PubMed

    Qian, Yushen; Von Eyben, Rie; Liu, Yufei; Chin, Frederick T; Miao, Zheng; Apte, Sandeep; Carter, Justin N; Binkley, Michael S; Pollom, Erqi L; Harris, Jeremy P; Prionas, Nicolas D; Kissel, Madelyn; Simmons, Amanda; Diehn, Maximilian; Shultz, David B; Brown, J Martin; Maxim, Peter G; Koong, Albert C; Graves, Edward E; Loo, Billy W

    2018-04-18

    Tumor hypoxia contributes to radiation resistance. A noninvasive assessment of tumor hypoxia would be valuable for prognostication and possibly selection for hypoxia-targeted therapies. 18 F-pentafluorinated etanidazole ( 18 F-EF5) is a nitroimidazole derivative that has demonstrated promise as a positron emission tomography (PET) hypoxia imaging agent in preclinical and clinical studies. However, correlation of imageable hypoxia by 18 F-EF5 PET with clinical outcomes after radiation therapy remains limited. Our study prospectively enrolled 28 patients undergoing radiation therapy for localized lung or other tumors to receive pretreatment 18 F-EF5 PET imaging. Depending on the level of 18 F-EF5 tumor uptake, patients underwent functional manipulation of tumor oxygenation with either carbogen breathing or oral dichloroacetate followed by repeated 18 F-EF5 PET. The hypoxic subvolume of tumor was defined as the proportion of tumor voxels exhibiting higher 18 F-EF5 uptake than the 95th percentile of 18 F-EF5 uptake in the blood pool. Tumors with a hypoxic subvolume ≥ 10% on baseline 18 F-EF5 PET imaging were classified as hypoxic by imaging. A Cox model was used to assess the correlation between imageable hypoxia and clinical outcomes after treatment. At baseline, imageable hypoxia was demonstrated in 43% of all patients (12 of 28), including 6 of 16 patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiation therapy and 6 of 12 patients with other cancers. Carbogen breathing was significantly associated with decreased imageable hypoxia, while dichloroacetate did not result in a significant change under our protocol conditions. Tumors with imageable hypoxia had a higher incidence of local recurrence at 12 months (30%) than those without (0%) (P < .01). Noninvasive hypoxia imaging by 18 F-EF5 PET identified imageable hypoxia in about 40% of tumors in our study population. Local tumor recurrence after highly conformal radiation

  6. 123I-MIBG scintigraphy and 18F-FDG-PET imaging for diagnosing neuroblastoma.

    PubMed

    Bleeker, Gitta; Tytgat, Godelieve A M; Adam, Judit A; Caron, Huib N; Kremer, Leontien C M; Hooft, Lotty; van Dalen, Elvira C

    2015-09-29

    Neuroblastoma is an embryonic tumour of childhood that originates in the neural crest. It is the second most common extracranial malignant solid tumour of childhood.Neuroblastoma cells have the unique capacity to accumulate Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG), which can be used for imaging the tumour. Moreover, ¹²³I-MIBG scintigraphy is not only important for the diagnosis of neuroblastoma, but also for staging and localization of skeletal lesions. If these are present, MIBG follow-up scans are used to assess the patient's response to therapy. However, the sensitivity and specificity of ¹²³I-MIBG scintigraphy to detect neuroblastoma varies according to the literature.Prognosis, treatment and response to therapy of patients with neuroblastoma are currently based on extension scoring of ¹²³I-MIBG scans. Due to its clinical use and importance, it is necessary to determine the exact diagnostic accuracy of ¹²³I-MIBG scintigraphy. In case the tumour is not MIBG avid, fluorine-18-fluorodeoxy-glucose ((18)F-FDG) positron emission tomography (PET) is often used and the diagnostic accuracy of this test should also be assessed. 1.1 To determine the diagnostic accuracy of ¹²³I-MIBG (single photon emission computed tomography (SPECT), with or without computed tomography (CT)) scintigraphy for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.1.2 To determine the diagnostic accuracy of negative ¹²³I-MIBG scintigraphy in combination with (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old, i.e. an add-on test. 2.1 To determine the diagnostic accuracy of (18)F-FDG-PET(-CT) imaging for detecting a neuroblastoma and its metastases at first diagnosis or at recurrence in children from 0 to 18 years old.2.2 To compare the diagnostic accuracy of ¹²³I-MIBG (SPECT-CT) and (18)F-FDG-PET

  7. Prospective evaluation of 18F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial).

    PubMed

    Jambor, Ivan; Kuisma, Anna; Kähkönen, Esa; Kemppainen, Jukka; Merisaari, Harri; Eskola, Olli; Teuho, Jarmo; Perez, Ileana Montoya; Pesola, Marko; Aronen, Hannu J; Boström, Peter J; Taimen, Pekka; Minn, Heikki

    2018-03-01

    The purpose of this study was to evaluate 18 F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq 18 F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV max ) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V T ). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV max and V T of Gleason score (GS) >3 + 4 tumors were significantly (p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes. Quantitative 18 F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. 18 F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI.

  8. The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

    PubMed

    Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

    2018-04-01

    The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

  9. [18F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson disease.

    PubMed

    Weng, Chi-Chang; Huang, Siao-Lan; Chen, Zi-An; Lin, Kun-Ju; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Kung, Mei-Ping; Wey, Shiaw-Pyng; Hsu, Ching-Han

    2017-08-01

    Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [ 18 F]9-fluoropropyl-(+)-dihydrotetrabenazine ([ 18 F]FP-(+)-DTBZ), a vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through positron emission tomography (PET) in lactacystin-treated rat brains. Adult male Sprague-Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 μg) or saline (served as the sham control) into the left medial forebrain bundle. A 30-min static [ 18 F]FP-(+)-DTBZ brain PET scan was performed following an intravenous [ 18 F]FP-(+)-DTBZ dose (approximately 22 MBq) in each animal at 2 and 3 weeks after lactacystin treatment. Upon completing the last PET scans, the animals were killed, and their brains were dissected for ex vivo autoradiography (ARG) and immunohistochemical (IHC) staining of tyrosine hydroxylase (TH) as well as VMAT2. Both the 2- and 5-μg lactacystin-treated groups exhibited significantly decreased specific [ 18 F]FP-(+)-DTBZ uptake in the ipsilateral striata (I-ST) at 2 weeks (1.51 and 1.16, respectively) and 3 weeks (1.36 and 1.00, respectively) after lactacystin treatment, compared with the uptake in the corresponding contralateral striata (C-ST) (3.48 and 3.08 for the 2- and 5-μg lactacystin-treated groups, respectively, at 2 weeks; 3.36 and 3.11 for the 2- and 5-μg lactacystin-treated groups, respectively, at 3 weeks) and the sham controls (3.34-3.53). Lactacystin-induced decline in I-ST [ 18 F]FP-(+)-DTBZ uptake was also demonstrated through ex vivo ARG, and the corresponding dopaminergic neuron damage was confirmed by the results of TH- and VMAT2-IHC studies. In this PD model, lactacystin-induced dopaminergic terminal damage in the ipsilateral striatum could be clearly visualized through in vivo [ 18 F]FP-(+)-DTBZ PET imaging. This may serve as a useful approach for evaluating the effectiveness of new

  10. 18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution.

    PubMed

    Wondergem, Maurits; van der Zant, Friso M; Knol, Remco J J; Lazarenko, Sergiy V; Pruim, Jan; de Jong, Igle J

    2017-11-01

    There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For 68 Ga-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For 18 F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of 18 F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer. Methods: Images were acquired 60 and 120 min after injection of 18 F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points. Results: Our data showed a significantly increasing uptake of 18 F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P < 0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-to-noise ratio of 11.93 was found for images acquired 120 min after injection ( P < 0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15). Conclusion: 18 F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate

  11. 18F-FEAnGA for PET of β-glucuronidase activity in neuroinflammation.

    PubMed

    Antunes, Inês F; Doorduin, Janine; Haisma, Hidde J; Elsinga, Philip H; van Waarde, Aren; Willemsen, Antoon T M; Dierckx, Rudi A; de Vries, Erik F J

    2012-03-01

    Activation of microglia is a hallmark of inflammatory, infectious, and degenerative diseases of the central nervous system. Several studies have indicated that there is an increase in release of β-glucuronidase by activated microglia into the extracellular space at the site of neuroinflammation. β-glucuronidase is involved in the hydrolysis of glycosaminoglycans on the cell surface and the degradation of the extracellular matrix. Therefore, β-glucuronidase might be a biomarker for ongoing neurodegeneration induced by neuroinflammation. In this study, we investigated whether the PET tracer (18)F-FEAnGA was able to detect β-glucuronidase release during neuroinflammation in a rat model of herpes encephalitis. Male Wistar rats were intranasally inoculated with herpes simplex virus 1 (HSV-1) or phosphate-buffered saline as a control. (11)C-(R)-PK11195 and (18)F-FEAnGA small-animal PET scans were acquired for 60 min. Logan graphical analysis was used to calculate (18)F-FEAnGA distribution volumes (DV(Logan)) in various brain areas. After administration of (18)F-FEAnGA, the area under the activity concentration-versus-time curve of the whole brain was 2 times higher in HSV-1-infected rats than in control rats. In addition, the DV(Logan) of (18)F-FEAnGA was most increased in the frontopolar cortex, frontal cortex, bulbus olfactorius, cerebral cortex, cerebellum, and brainstem of HSV-1-infected rats, when compared with control rats. The conversion of (18)F-FEAnGA to 4-hydroxy-3-nitrobenzyl alcohol was found to be 1.6 times higher in HSV-1-infected rats than in control rats and correlated with the DV(Logan) of (18)F-FEAnGA in the same areas of the brain. Furthermore, the DV(Logan) of (18)F-FEAnGA also correlated with β-glucuronidase activity in the same brain regions. In addition, DV(Logan) of (18)F-FEAnGA showed a tendency to correlate with (11)C-(R)-PK11195 uptake (marker for activated microglia) in the same brain regions. Despite relatively low brain uptake, (18)F

  12. The influence of interpreters' professional background and experience on the interpretation of multimodality imaging of pulmonary lesions using 18F-3'-deoxy-fluorothymidine and 18F-fluorodeoxyglucose PET/CT.

    PubMed

    Xu, Bai-xuan; Liu, Chang-bin; Wang, Rui-min; Shao, Ming-zhe; Fu, Li-ping; Li, Yun-gang; Tian, Jia-he

    2013-01-01

    Based on the results of a recently accomplished multicenter clinical trial for the incremental value of a dual-tracer (18F-FDG and 18F-FLT), dual-modality (PET and CT) imaging in the differential diagnosis of pulmonary lesions, we investigate some issues that might affect the image interpretation and result reporting. The images were read in two separate sessions. Firstly the images were read and reported by physician(s) of the imaging center on completion of each PET/CT scanning. By the end of MCCT, all images collected during the trial were re-read by a collective of readers in an isolated, blinded, and independent way. One hundred sixty two patients successfully passed the data verification and entered into the final analysis. The primary reporting result showed adding 18F-FDG image information did not change the clinical performance much in sensitivity, specifity and accuracy, but the ratio between SUVFLT and SUVFDG did help the differentiation efficacy among the three subgroups of patients. The collective reviewing result showed the diagnostic achievement varied with reading strategies. ANOVA indicated significant differences among (18)F-FDG, (18)F-FLT in SUV (F = 14.239, p = 0.004). CT had almost the same diagnostic performance as 18F-FLT. When the 18F-FDG, 18F-FLT and CT images read in pair, both diagnostic sensitivity and specificity improved. The best diagnostic figures were obtained in full-modality strategy, when dual-tracer PET worked in combination with CT. With certain experience and training both radiologists and nuclear physicians are qualified to read and to achieve the similar diagnostic accuracy in PET/CT study. Making full use of modality combination and selecting right criteria seems more practical than professional back ground and personal experience in the new hybrid imaging technology, at least when novel tracer or application is concerned.

  13. Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein.

    PubMed

    Fan, Zhen; Calsolaro, Valeria; Atkinson, Rebecca A; Femminella, Grazia D; Waldman, Adam; Buckley, Christopher; Trigg, William; Brooks, David J; Hinz, Rainer; Edison, Paul

    2016-11-01

    Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide ( 18 F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18 F-GE180 PET in (older) healthy controls. Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18 F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. 18 F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (V T ) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18 F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a V T highly consistent with V T in the kinetic model, which could be used for voxelwise analysis. We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18 F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps

  14. Feasibility of assessing [(18)F]FDG lung metabolism with late dynamic PET imaging.

    PubMed

    Laffon, Eric; de Clermont, Henri; Vernejoux, Jean-Marc; Jougon, Jacques; Marthan, Roger

    2011-04-01

    The aim of this work was to non-invasively establish the feasibility of assessing 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) lung metabolism with the use of a late dynamic positron emission tomograpy (PET) acquisition, i.e., beyond 2 h after injection. The present method has been probed in 11 patients without any respiratory disease, under fasting conditions, by assessing mean values of (18)F-FDG lung metabolism. A kinetic model analysis has been implemented on a simple calculation sheet. An arbitrary (population based) input function has been used in each individual, which was obtained from literature data. In the healthy lung, no (18)F-FDG release was found, and the mean values (±SD) of the (18)F-FDG uptake rate constant and of the fraction of the free tracer in blood and interstitial volume were: K = 0.0016 min(-1) (±0.0005), and F = 0.18 (±0.10), respectively. These results were in very close agreement with literature data that were obtained by both three-compartment model analysis and Patlak graphical analysis (gold standards), and that used an invasive blood sampling. Furthermore, K and the standard uptake value index have been compared. We conclude that assessing lung metabolism of (18)F-FDG in humans with the use of late dynamic PET imaging is feasible. The arbitrary input function of this non-invasive feasibility study could be replaced in further experiments by an input function obtained by arterial sampling. It is suggested that this method may prove useful to quantify (18)F-FDG lung metabolism under pathological conditions.

  15. Risk-related 18F-FDG PET/CT and new diagnostic strategies in patients with solitary pulmonary nodule: the ITALIAN multicenter trial.

    PubMed

    Spadafora, Marco; Pace, Leonardo; Evangelista, Laura; Mansi, Luigi; Del Prete, Francesco; Saladini, Giorgio; Miletto, Paolo; Fanti, Stefano; Del Vecchio, Silvana; Guerra, Luca; Pepe, Giovanna; Peluso, Giuseppina; Nicolai, Emanuele; Storto, Giovanni; Ferdeghini, Marco; Giordano, Alessandro; Farsad, Mohsen; Schillaci, Orazio; Gridelli, Cesare; Cuocolo, Alberto

    2018-05-05

    Diagnosis of solitary pulmonary nodule (SPN) is an important public health issue and 18 F-FDG PET/CT has proven to be more effective than CT alone. Pre-test risk stratification and clinical presentation of SPN could affect the diagnostic strategy. A relevant issue is whether thoracic segmental (s)-PET/CT could be implemented in patients with SPN. This retrospective multicenter study compared the results of FDG whole-body (wb)-PET/CT to those of s-PET/CT. 18 F-FDG PET/CT of 502 patients, stratified for pre-test cancer risk, were retrospectively analyzed. The thoracic part of wb-PET/CT, considered s-PET/CT, was compared to wb-PET/CT. Clinical and PET/CT variables were investigated for SPN characterization as well as for identification of patients in whom s-PET/CT could be performed. Histopathology or follow-up data were used as a reference. In the study population, 36% had malignant, 35% benign, and 29% indeterminate SPN. 18 F-FDG uptake indicative of thoracic and extra-thoracic lesions was detectable in 13% and 3% of the patients. All patients with extra-thoracic metastases (n = 13) had thoracic lymph node involvement and highest 18 F-FDG uptake at level of SPN (negative predictive value 100%). Compared to wb-PET/CT, s-PET/CT could save about 2/3 of 18 F-FDG dose, radiation exposure or scan-time, without affecting the clinical impact of PET/CT. Pre-test probability of malignancy can guide the diagnostic strategy of 18 FDG-PET/CT in patients with SPN. In subjects with low-intermediate pretest probability s-PET/CT imaging might be planned in advance, while in those at high risk and with thoracic lymph node involvement a wb-PET/CT is necessary.

  16. Dual acquisition of 18F-FMISO and 18F-FDOPA

    NASA Astrophysics Data System (ADS)

    Bell, Christopher; Rose, Stephen; Puttick, Simon; Pagnozzi, Alex; Poole, Christopher M.; Gal, Yaniv; Thomas, Paul; Fay, Michael; Jeffree, Rosalind L.; Dowson, Nicholas

    2014-07-01

    Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

  17. Radiation exposure to nuclear medicine staffs during 18F-FDG PET/CT procedures at Ramathibodi Hospital

    NASA Astrophysics Data System (ADS)

    Donmoon, T.; Chamroonrat, W.; Tuntawiroon, M.

    2016-03-01

    The aim of this study is to estimate the whole body and finger radiation doses per study received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during PET/CT imaging procedures in a PET/CT facility. The whole-body doses received by radiopharmacists, technologists and nurses were measured by electronic dosimeter and the finger doses by ring dosimeter during a period of 4 months. In 70 PET/CT studies, the mean whole-body dose per study to radiopharmacist, technologist, and nurse were 1.07±0.09, 1.77±0.46, μSv, and not detectable respectively. The mean finger doses per study received by radiopharmacist, technologist, and nurse were 265.65±107.55, 4.84±1.08 and 19.22±2.59 μSv, respectively. The average time in contact with 18F-FDG was 5.88±0.03, 39.06±1.89 and 1.21±0.02 minutes per study for radiopharmacist, technologist and nurse respectively. Technologists received highest mean effective whole- body dose per study and radiopharmacist received the highest finger dose per study. When compared with the ICRP dose limit, each individual worker can work with many more 18F- FDG PET/CT studies for a whole year without exceeding the occupational dose limits. This study confirmed that low levels of radiation does are received by our medical personnel involved in 18F-FDG PET/CT procedures.

  18. Diagnostic accuracy of 18F-FDG-PET and PET/CT in the differential diagnosis between malignant and benign pleural lesions: a systematic review and meta-analysis.

    PubMed

    Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Bertagna, Francesco; Prior, John O; Ceriani, Luca; Giovanella, Luca

    2014-01-01

    To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  19. Comparison of 18F-Labeled Fluoroalkylphosphonium Cations with 13N-NH3 for PET Myocardial Perfusion Imaging.

    PubMed

    Kim, Dong-Yeon; Kim, Hyeon Sik; Reder, Sybille; Zheng, Jin Hai; Herz, Michael; Higuchi, Takahiro; Pyo, A Young; Bom, Hee-Seung; Schwaiger, Markus; Min, Jung-Joon

    2015-10-01

    Despite substantial advances in the diagnosis of cardiovascular disease, there is a need for 18F-labeled myocardial perfusion agents for the diagnosis of ischemic heart disease because current PET tracers for myocardial perfusion imaging have a short half-life that limits their widespread clinical use in PET. Thus, 18F-labeled fluoroalkylphosphonium derivatives (18F-FATPs), including (5-18F-fluoropentyl)triphenylphosphonium cation (18F-FPTP), (6-18F-fluorohexyl)triphenylphosphonium cation (18F-FHTP), and (2-(2-18F-fluoroethoxy)ethyl)triphenylphosphonium cation (18F-FETP), were synthesized. The myocardial extraction and image quality of the 18F-FATPs were compared with those of 13N-NH3 in rat models. The first-pass extraction fraction (EF) values of the 18F-FATPs (18F-FPTP, 18F-FHTP, 18F-FETP) and 13N-NH3 were measured in isolated rat hearts perfused with the Langendorff method (flow velocities, 0.5, 4.0, 8.0, and 16.0 mL/min). Normal and myocardial infarction rats were imaged with small-animal PET after intravenous injection of 37 MBq of 18F-FATPs and 13N-NH3. To determine pharmacokinetics, a region of interest was drawn around the heart, and time-activity curves of the 18F-FATPs and 13N-NH3 were generated to obtain the counts per pixel per second. Defect size was analyzed on the basis of polar map images of 18F-FATPs and 13N-NH3. The EF values of 18F-FATPs and 13N-NH3 were comparable at low flow velocity (0.5 mL/min), whereas at higher flows EF values of 18F-FATPs were significantly higher than those of 13N-NH3 (4.0, 8.0, and 16.0 mL/min, P<0.05). Myocardium-to-liver ratios of 18F-FPTP, 18F-FHTP, 18F-FETP, and 13N-NH3 were 2.10±0.30, 4.36±0.20, 3.88±1.03, and 0.70±0.09, respectively, 10 min after injection, whereas myocardium-to-lung ratios were 5.00±0.25, 4.33±0.20, 7.98±1.23, and 2.26±0.14, respectively. Although 18F-FATPs and 13N-NH3 sharply delineated myocardial perfusion defects, defect size on the 13N-NH3 images was significantly smaller than on the

  20. Multimodal 18F-Fluciclovine PET/MRI and Ultrasound-Guided Neurosurgery of an Anaplastic Oligodendroglioma.

    PubMed

    Karlberg, Anna; Berntsen, Erik Magnus; Johansen, Håkon; Myrthue, Mariane; Skjulsvik, Anne Jarstein; Reinertsen, Ingerid; Esmaeili, Morteza; Dai, Hong Yan; Xiao, Yiming; Rivaz, Hassan; Borghammer, Per; Solheim, Ole; Eikenes, Live

    2017-12-01

    Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracer 18 F-fluciclovine ( 18 F-FACBC) for intraoperative image-guided surgery. A previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II. 18 F-Fluciclovine uptake was found in parts of the tumor where regional WHO grade, cell proliferation, and cell densities were highest. This finding suggests that PET/MRI with this tracer could be used to improve accuracy in histopathologic tissue sampling and grading, and possibly for guiding treatments targeting the most malignant part of extensive and eloquent gliomas. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Comparative uptake of ¹⁸F-FEN-DPAZn2, ¹⁸F-FECH, ¹⁸F-fluoride, and ¹⁸F-FDG in fibrosarcoma and aseptic inflammation.

    PubMed

    Liang, Xiang; Tang, Ganghua; Wang, Hongliang; Hu, Kongzhen; Tang, Xiaolan; Nie, Dahong; Sun, Ting; Huang, Tingting

    2014-08-01

    The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)-dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the combined S180 fibrosarcoma and turpentine-induced inflammation mice models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation-to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the best selectivity to inflammation. (18)F-FECH positron emission tomography (PET) imaging demonstrates some advantages over (18)F-FDG PET for the differentiation of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for PET imaging of aseptic inflammation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

    PubMed

    Mayoral, M; Fernandez-Martinez, A; Vidal, L; Fuster, D; Aya, F; Pavia, J; Pons, F; Lomeña, F; Paredes, P

    2016-01-01

    Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  3. A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images.

    PubMed

    Wang, Ping; Xu, Wengui; Sun, Jian; Yang, Chengwen; Wang, Gang; Sa, Yu; Hu, Xin-Hua; Feng, Yuanming

    2016-01-01

    It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after

  4. Subclinical seizures as a pitfall in 18F-FDG PET imaging of temporal lobe epilepsy.

    PubMed

    Tafti, Bashir Akhavan; Mandelkern, Mark; Berenji, Gholam Reza

    2014-09-01

    A 61-year-old man with history of heroin abuse, hepatitis B, hepatitis C, and hypertension was evaluated for seizures. MRI findings were concerning for temporal epilepsy. A brain 18F-FDG PET study showed a hypermetabolic focus in the left temporal lobe, although the patient was asymptomatic during the scan. Later review of electroencephalography recordings revealed a subclinical seizure during imaging. A whole-body 18F-FDG PET scan performed 4 days later for cancer screening purposes, during which the electroencephalography tracings were normal, showed no abnormal metabolic activity in the brain.

  5. (18)F-FDG PET/CT for the detection of large vessel vasculitis in patients with polymyalgia rheumatica.

    PubMed

    Lavado-Pérez, C; Martínez-Rodríguez, I; Martínez-Amador, N; Banzo, I; Quirce, R; Jiménez-Bonilla, J; De Arcocha-Torres, M; Bravo-Ferrer, Z; Jiménez-Alonso, M; López-Defilló, J L; Blanco, R; González-Gay, M A; Carril, J M

    2015-01-01

    Polymyalgia rheumatica (PMR) may present together with large vessel vasculitis (LVV), and frequently requires a more intensive therapy. The aim of the study was to evaluate the impact of (18)F-FDG PET/CT in the diagnosis and management of LVV associated to PMR. This prospective study included 40 consecutive patients (27 women/13 men, 68.10±10.27 years) with PMR and suspicion of associated LVV submitted for (18)F-FDG PET/CT. A PET/CT scan was obtained 180 min after (18)F-FDG intravenous injection. A visual analysis was performed on the images. Five vascular regions were evaluated: supra-aortic trunks (SAT), thoracic aorta (TA), abdominal aorta (AA), iliac arteries (IA), and femoral/tibioperoneal arteries (FTA). The intensity of uptake was graded from 0 to 3. A final diagnosis of LVV was established in 26/40 patients (65%). In the 26 patients with a diagnosis of LVV, the highest intensity of (18)F-FDG uptake was observed in the TA, SAT, and FTA. All of these patients showed uptake at the TA, with grade 2 and 3 in most cases. In 4 of the 14 patients without LVV, no uptake was observed in any vascular region, and in the other 10 patients only a grade 1 uptake was observed in 1 or to 2 territories. Out of the 20 treated LVV patients, (18)F-FDG PET/CT led to a therapeutic change in 17 (85%). (18)F-FDG PET/CT was useful in identifying patients with LVV associated to PMR. The detection of vascular inflammation had an important impact, and led to a change of treatment in a high percentage of patients with LVV. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  6. Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

    PubMed

    Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

    2014-05-01

    Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant

  7. 11C-Choline-Pet Guided Stereotactic Body Radiation Therapy for Lymph Node Metastases in Oligometastatic Prostate Cancer.

    PubMed

    Franzese, Ciro; Lopci, Egesta; Di Brina, Lucia; D'Agostino, Giuseppe Roberto; Navarria, Pierina; Mancosu, Pietro; Tomatis, Stefano; Chiti, Arturo; Scorsetti, Marta

    2017-10-21

    aim is outcome of 11C-Choline-PET guided SBRT on lymph node metastases. patients with 1 - 4 lymph node metastases detected by 11C-choline-PET were treated with SBRT. Toxicity, treated metastases control and Progression Free Survival were computed. twenty-six patients, 38 lymph node metastases were irradiated. No grade ≥ 2 toxicity. Median PSA-nadir after RT was 1.02 ng/mL. Post-treatment 11C-Choline-PET showed metabolic complete response in 17 metastases (44,7%), partial response in 9 metastases (38%). SBRT is effective and safe for lymph node metastases. PET is important in identification of gross tumor and evaluation of the response.

  8. 18F-FDG PET of the hands with a dedicated high-resolution PEM system (arthro-PET): correlation with PET/CT, radiography and clinical parameters

    PubMed Central

    Mhlanga, Joyce C.; Carrino, John A.; Lodge, Martin; Wang, Hao

    2015-01-01

    Purpose The aim of this study was to prospectively determine the feasibility and compare the novel use of a positron emission mammography (PEM) scanner with standard PET/CT for evaluating hand osteoarthritis (OA) with 18F-FDG. Methods Institutional review board approval and written informed consent were obtained for this HIPAA-compliant prospective study in which 14 adults referred for oncological 18F-FDG PET/CT underwent dedicated hand PET/CT followed by arthro-PET using the PEM device. Hand radiographs were obtained and scored for the presence and severity of OA. Summed qualitative and quantitative joint glycolytic scores for each modality were compared with the findings on plain radiography and clinical features. Results Eight patients with clinical and/or radiographic evidence of OA comprised the OA group (mean age 73±7.7 years). Six patients served as the control group (53.7±9.3 years). Arthro-PET quantitative and qualitative joint glycolytic scores were highly correlated with PET/CT findings in the OA patients (r=0.86. p =0.007; r=0.94, p=0.001). Qualitative arthro-PET and PET/CT joint scores were significantly higher in the OA patients than in controls (38.7±6.6 vs. 32.2±0.4, p=0.02; 37.5±5.4 vs. 32.2±0.4, p=0.03, respectively). Quantitative arthro-PET and PET/CT maximum SUV-lean joint scores were higher in the OA patients, although they did not reach statistical significance (20.8±4.2 vs. 18±1.8, p= 0.13; 22.8±5.38 vs. 20.1±1.54, p=0.21). By definition, OA patients had higher radiographic joint scores than controls (30.9±31.3 vs. 0, p=0.03). Conclusion Hand imaging using a small field of view PEM system (arthro-PET) with FDG is feasible, performing comparably to PET/CT in assessing metabolic joint activity. Arthro-PET and PET/CT showed higher joint FDG uptake in OA. Further exploration of arthro-PET in arthritis management is warranted. PMID:25134669

  9. Generalized Lymph Node Activation after Influenza Vaccination on 18F FDG-PET/CT Imaging, an Important Pitfall in PET Interpretation.

    PubMed

    Ayati, Narjess; Jesudason, Sarah; Berlangieri, Salvatore U; Scott, Andrew M

    2017-01-01

    We report on a 59-year-old female patient with an infected vascular graft investigated with 18 F FDG-PET/CT. The first of two studies showed FDG activity in the left deltoid and ipsilateral axillary lymph nodes explained by influenza vaccination the day prior. The second 18 F FDG-PET/CT showed multiple FDG-avid lymph nodes on both sides of the diaphragm without tracer accumulation at the vaccination site. Three months later the CT was negative for lymphadenopathy within the chest or abdominal region. Although influenza vaccination is a potential source of false positive results in FDG PET studies, generalised lymph node activation post vaccination is a rare finding with only one prior published report in individuals infected with HIV-1. This case emphasizes the necessity of taking a history of vaccination prior to a FDG PET study, and consideration of a vaccine-related immune response even without evidence of tracer activity at the vaccination site when generalised FDG-avid lymphadenopathy is encountered.

  10. A Comparison between 18F-FDG PET/CT Imaging and Biological and Radiological Findings in Restaging of Hepatoblastoma Patients

    PubMed Central

    Treglia, Giorgio; Pagano, Manuela; Fania, Piercarlo; Basso, Maria Eleonora; Fagioli, Franca; Ficola, Umberto

    2013-01-01

    Background. In this study we retrospectively evaluated if 18F-FDG-PET/CT provided incremental diagnostic information over CI in a group of hepatoblastoma patients performing restaging. Procedure. Nine patients (mean age: 5.9 years; range: 3.1–12 years) surgically treated for hepatoblastoma were followed up by clinical examination, serum α-FP monitoring, and US. CI (CT or MRI) and PET/CT were performed in case of suspicion of relapse. Fine-needle aspiration biopsies (FNAB) were carried out for final confirmation if the results of CI, PET/CT, and/or α-FP levels were suggestive of relapse. PET/CT and CI findings were analyzed for comparison purposes, using FNAB as reference standard. Results. α-FP level was suggestive of disease recurrence in 8/9 patients. Biopsy was performed in 8/9 cases. CI and PET/CT resulted to be concordant in 5/9 patients (CI identified recurrence of disease, but 18F-FDG-PET/CT provided a better definition of disease extent); in 4/9 cases, CI diagnostic information resulted in negative findings, whereas PET/CT correctly detected recurrence of disease. 18F-FDG-PET/CT showed an agreement of 100% (8/8) with FNAB results. Conclusions. 18F-FDG-PET/CT scan seems to better assess HB patients with respect to CI and may provide incremental diagnostic value in the restaging of this group of patients. PMID:24063012

  11. Evaluation of Prostate Cancer with 11C-Choline PET/CT for Treatment Planning, Response Assessment, and Prognosis.

    PubMed

    Ceci, Francesco; Castellucci, Paolo; Mapelli, Paola; Incerti, Elena; Picchio, Maria; Fanti, Stefano

    2016-10-01

    The aim of this review is to report on the value of 11 C-choline PET imaging as a diagnostic procedure for metastasis-directed therapies. Furthermore, the role of 11 C-choline PET/CT as a diagnostic tool for monitoring castration-resistant prostate cancer patients treated with systematic therapy is assessed. Finally, the role of 11 C-choline PET/CT in the prediction of survival in both castration-resistant prostate cancer patients and hormone-naïve patients is investigated. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  12. (18)F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: A pilot study.

    PubMed

    Cistaro, A; Cucinotta, M; Cassalia, L; Priola, A; Priola, S; Pappalardo, M; Coppolino, P; De Simone, M; Quartuccio, N

    2016-01-01

    Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography ((18)F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal(18)F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery (18)F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by (18)F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased (18)F-FDG uptake, were recognized. PP+IPCH of patients selected by (18)F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample.

    PubMed

    La Joie, Renaud; Bejanin, Alexandre; Fagan, Anne M; Ayakta, Nagehan; Baker, Suzanne L; Bourakova, Viktoriya; Boxer, Adam L; Cha, Jungho; Karydas, Anna; Jerome, Gina; Maass, Anne; Mensing, Ashley; Miller, Zachary A; O'Neil, James P; Pham, Julie; Rosen, Howard J; Tsai, Richard; Visani, Adrienne V; Miller, Bruce L; Jagust, William J; Rabinovici, Gil D

    2018-01-23

    To assess the relationships between fluid and imaging biomarkers of tau pathology and compare their diagnostic utility in a clinically heterogeneous sample. Fifty-three patients (28 with clinical Alzheimer disease [AD] and 25 with non-AD clinical neurodegenerative diagnoses) underwent β-amyloid (Aβ) and tau ([ 18 F]AV1451) PET and lumbar puncture. CSF biomarkers (Aβ 42 , total tau [t-tau], and phosphorylated tau [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator characteristic analyses were performed to compare discrimination of Aβ-positive AD from non-AD conditions across biomarkers. Correlations between CSF biomarkers and PET standardized uptake value ratios (SUVR) were assessed using skipped Pearson correlation coefficients. Voxelwise analyses were run to assess regional CSF-PET associations. [ 18 F]AV1451-PET cortical SUVR and p-tau showed excellent discrimination between Aβ-positive AD and non-AD conditions (area under the curve 0.92-0.94; ≤0.83 for other CSF measures), and reached 83% classification agreement. In the full sample, cortical [ 18 F]AV1451 was associated with all CSF biomarkers, most strongly with p-tau ( r = 0.75 vs 0.57 for t-tau and -0.49 for Aβ 42 ). When restricted to Aβ-positive patients with AD, [ 18 F]AV1451 SUVR correlated modestly with p-tau and t-tau (both r = 0.46) but not Aβ 42 ( r = 0.02). On voxelwise analysis, [ 18 F]AV1451 correlated with CSF p-tau in temporoparietal cortices and with t-tau in medial prefrontal regions. Within AD, Mini-Mental State Examination scores were associated with [ 18 F]AV1451-PET, but not CSF biomarkers. [ 18 F]AV1451-PET and CSF p-tau had comparable value for differential diagnosis. Correlations were robust in a heterogeneous clinical group but attenuated (although significant) in AD, suggesting that fluid and imaging biomarkers capture different aspects of tau pathology. This study provides Class III evidence that, in a clinical sample of patients with a variety

  14. Comparison between endoscopic macroscopic classification and F-18 FDG PET findings in gastric mucosa-associated lymphoid tissue lymphoma patients.

    PubMed

    Hirose, Yasumitsu; Kaida, Hayato; Ishibashi, Masatoshi; Uozumi, Jun; Arikawa, Shunji; Kurata, Seiji; Hayabuchi, Naofumi; Nakahara, Keita; Ohshima, Koichi

    2012-02-01

    The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis-like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis-like tumors and 40% for depressed-type tumors. F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.

  15. Characterization in humans of 18F-MNI-444, a PET radiotracer for brain adenosine 2A receptors.

    PubMed

    Barret, Olivier; Hannestad, Jonas; Vala, Christine; Alagille, David; Tavares, Adriana; Laruelle, Marc; Jennings, Danna; Marek, Ken; Russell, David; Seibyl, John; Tamagnan, Gilles

    2015-04-01

    PET with selective adenosine 2A receptor (A2A) radiotracers can be used to study a variety of neurodegenerative and neuropsychiatric disorders in vivo and to support drug-discovery studies targeting A2A. The aim of this study was to describe the first in vivo evaluation of (18)F-MNI-444, a novel PET radiotracer for imaging A2A, in healthy human subjects. Ten healthy human volunteers were enrolled in this study; 6 completed the brain PET studies and 4 participated in the whole-body PET studies. Arterial blood was collected for invasive kinetic modeling of the brain PET data. Noninvasive methods of data quantification were also explored. Test-retest reproducibility was evaluated in 5 subjects. Radiotracer distribution and dosimetry was determined using serial whole-body PET images acquired over 6 h post-radiotracer injection. Urine samples were collected to calculate urinary excretion. After intravenous bolus injection, (18)F-MNI-444 rapidly entered the brain and displayed a distribution consistent with known A2A densities in the brain. Binding potentials ranging from 2.6 to 4.9 were measured in A2A-rich regions, with an average test-retest variability of less than 10%. The estimated whole-body radiation effective dose was approximately 0.023 mSv/MBq. (18)F-MNI-444 is a useful PET radiotracer for imaging A2A in the human brain. The superior in vivo brain kinetic properties of (18)F-MNI-444, compared with previously developed A2A radiotracers, provide the opportunity to foster global use of in vivo A2A PET imaging in neuroscience research. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  16. Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

    PubMed

    Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

    2013-01-01

    This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K(1), and k(3) to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021), irrespective of stage and resectability. Quantitative (18)F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single

  17. 18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective.

    PubMed

    Meintjes, Marguerite; Endozo, Raymond; Dickson, John; Erlandsson, Kjel; Hussain, Khalid; Townsend, Caroline; Menezes, Leon; Bomanji, Jamshed

    2013-06-01

    Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of (18)F-DOPA PET/CT images in our clinical practice. Twenty-two (18)F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1-84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. (18)F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. (18)F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. Of the 18 patients, 13 showed diffuse and five showed focal (18)F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUV(max). Using the formula - highest SUV(max)/next highest SUV(max) - a ratio was calculated. Five patients had

  18. New horizons in cardiac innervation imaging: introduction of novel 18F-labeled PET tracers.

    PubMed

    Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A; Lapa, Constantin; Javadi, Mehrbod S; Higuchi, Takahiro

    2017-12-01

    Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed.

  19. [18F]MEL050 as a melanin-targeted PET tracer: Fully automated radiosynthesis and comparison to 18F-FDG for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases.

    PubMed

    Rizzo-Padoin, Nathalie; Chaussard, Michael; Vignal, Nicolas; Kotula, Ewa; Tsoupko-Sitnikov, Vadim; Vaz, Sofia; Hontonnou, Fortune; Liu, Wang-Qing; Poyet, Jean-Luc; Vidal, Michel; Merlet, Pascal; Hosten, Benoit; Sarda-Mantel, Laure

    2016-12-01

    Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [ 18 F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [ 18 F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [ 18 F]FDG. Automated radiosynthesis of [ 18 F]MEL050, including HPLC purification and formulation, were performed on an AllInOne™ synthesis module. [ 18 F]MEL050 was synthesized using a one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumor) or intravenous (pulmonary metastases) injection of B16-F10-luc2 cells in NMRI mice. The maximum percentage of [ 18 F]MEL050 Injected Dose per g of lung tissue (%ID/g Max) was determined on PET images, compared to [ 18 F]FDG and correlated to in vivo bioluminescence imaging. The automated radiosynthesis of [ 18 F]MEL050 required an overall radiosynthesis time of 48min, with a yield of 13-18% (not-decay corrected) and radiochemical purity higher than 99%. [ 18 F]MEL050 PET/CT images were concordant with bioluminescence imaging, showing increased radiotracer uptake in all primary subcutaneous tumors and pulmonary metastases of mice. PET quantification of radiotracers uptake in tumors and muscles demonstrated similar tumor-to-background ratio (TBR) with [ 18 F]MEL050 and [ 18 F]FDG in subcutaneous tumors and higher TBR with [ 18 F]MEL050 than with [ 18 F]FDG in pulmonary metastases. We successfully implemented the radiosynthesis of [ 18 F]MEL050 using the AllInOne™ module, including HPLC purification and formulation. In vivo PET/CT validation of [ 18 F]MEL050 was obtained in mouse models of pigmented melanoma, where higher [ 18 F]MEL050 uptake was observed

  20. 18F-FAC PET selectively images hepatic infiltrating CD4 and CD8 T cells in a mouse model of autoimmune hepatitis.

    PubMed

    Salas, Jessica R; Chen, Bao Ying; Wong, Alicia; Cheng, Donghui; Van Arnam, John S; Witte, Owen N; Clark, Peter M

    2018-04-26

    Immune cell-mediated attack on the liver is a defining feature of autoimmune hepatitis and hepatic allograft rejection. Despite an assortment of diagnostic tools, invasive biopsies remain the only method for identifying immune cells in the liver. We evaluated whether PET imaging with radiotracers that quantify immune activation ( 18 F-FDG and 18 F-FAC) and hepatocyte biology ( 18 F-DFA) can visualize and quantify hepatic infiltrating immune cells and hepatocyte inflammation, respectively, in a preclinical model of autoimmune hepatitis. Methods: Mice treated with Concanavalin A (ConA) to induce a model of autoimmune hepatitis or vehicle were imaged with 18 F-FDG, 18 F-FAC, and 18 F-DFA PET. Immunohistochemistry, digital autoradiography, and ex vivo accumulation assays were used to localize areas of altered radiotracer accumulation in the liver. For comparison, mice treated with an adenovirus to induce a viral hepatitis or vehicle were imaged with 18 F-FDG, 18 F-FAC, and 18 F-DFA PET. 18 F-FAC PET was performed on mice treated with ConA, and vehicle or dexamethasone. Biopsy samples of patients suffering from autoimmune hepatitis were immunostained for deoxycytidine kinase (dCK). Results: Hepatic accumulation of 18 F-FDG and 18 F-FAC was 173% and 61% higher, respectively, and hepatic accumulation of 18 F-DFA was 41% lower in a mouse model of autoimmune hepatitis compared to control mice. Increased hepatic 18 F-FDG accumulation was localized to infiltrating leukocytes and inflamed sinusoidal endothelial cells, increased hepatic 18 F-FAC accumulation was concentrated in infiltrating CD4 and CD8 cells, and decreased hepatic 18 F-DFA accumulation was apparent in hepatocytes throughout the liver. In contrast, viral hepatitis increased hepatic 18 F-FDG accumulation by 109% and decreased hepatic 18 F-DFA accumulation by 20% but had no effect on hepatic 18 F-FAC accumulation (non-significant 2% decrease). 18 F-FAC PET provided a non-invasive biomarker of the efficacy of

  1. PET/CT study performed after an oral administration of 18F-fluoride.

    PubMed

    Zacchi, Samara Riguete; Valadares, Agnes Araújo; Duarte, Paulo Schiavom; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

    2013-12-01

    A 52-year-old woman with right breast cancer was referred for 18F-fluoride whole-body PET/CT for the assessment of bone metastases. The peripheral i.v. access was not obtained after multiple attempts. The radiopharmaceutical was administered by oral route.

  2. Heterogeneity in Intratumor Correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET in Canine Sinonasal Tumors

    PubMed Central

    Bradshaw, Tyler J.; Bowen, Stephen R.; Jallow, Ngoneh; Forrest, Lisa J.; Jeraj, Robert

    2014-01-01

    Intratumor heterogeneity in biologic properties and in relationships between various phenotypes may present a challenge for biologically targeted therapies. Understanding the relationships between different phenotypes in individual tumor types could help inform treatment selection. The goal of this study was to characterize spatial correlations of glucose metabolism, proliferation, and hypoxia in 2 histologic types of tumors. Methods Twenty canine veterinary patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7 sarcomas) were imaged with 18F-FDG, 18F-labeled 39-deoxy-39-fluorothymidine (18F-FLT), and 61Cu-labeled diacetyl-bis(N4-methylthiosemicarbazone) (61Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and immobilization techniques coupled with anesthesia enabled motionless scans with repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and carcinoma volumes were compared by use of Mann– Whitney U tests. Patient images were rigidly registered together, and intratumor tracer uptake distributions were compared. Voxel-based Spearman correlation coefficients were used to quantify intertracer correlations, and the correlation coefficients of sarcomas and carcinomas were compared. The relative overlap of the highest uptake volumes of the 3 tracers was quantified, and the values were compared for sarcomas and carcinomas. Results Large degrees of heterogeneity in SUV measures and phenotype correlations were observed. Carcinoma and sarcoma tumors differed significantly in SUV measures, with carcinoma tumors having significantly higher 18F-FDG maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher 61Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly higher population-averaged Spearman correlation coefficients than sarcomas in comparisons of 18F-FDG and 18F-FLT (0.80 vs. 0.61; P = 0.02), 18F-FLT and 61Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and 18F-FDG and 61Cu-ATSM (0.82 vs. 0

  3. Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

    PubMed

    Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

    2018-01-01

    Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in

  4. Extramedullary Solitary Plasmacytoma: Demonstrating the Role of 18F-FDG PET Imaging.

    PubMed

    Gautam, Archana; Sahu, Kamal Kant; Alamgir, Ahsan; Siddiqi, Imran; Ailawadhi, Sikander

    2017-04-01

    An Extramedullary Plasmacytoma (EMP) is characterized by a neoplastic proliferation of clonal plasma cells outside the medullary cavity. EMPs are a rare occurrence compared to other malignant plasma cell disorders and account for approximately 3-5% of plasma-cell neoplasms. Although most cases of EMP are not immediately life threatening at diagnosis, EMPs can progress to Multiple Myeloma (MM) and thus, warrant monitoring. Currently, there are no standard guidelines for when and how to monitor patients who are diagnosed with or treated for a solitary plasmacytoma. We present a case of solitary EMP who was treated adequately and definitively but developed a distinct, non-contiguous subsequent solitary EMP and was only discovered due to surveillance 18 F-Fludeoxyglucose Positron Emission Tomography ( 18 F-FDG) (PET) scan. Uniform surveillance guidelines should be developed and the potential benefits of PET and other imaging techniques as well as their cost should be considered.

  5. Utility of 18 F-FDG PET/CT scan to diagnose the etiology of fever of unknown origin in patients on dialysis.

    PubMed

    Tek Chand, Kalawat; Chennu, Krishna Kishore; Amancharla Yadagiri, Lakshmi; Manthri Gupta, Ranadheer; Rapur, Ram; Vishnubotla, Siva Kumar

    2017-04-01

    Studies on fever of unknown origin (FUO) in patients of chronic kidney disease and end stage renal disease patients on dialysis were not many. In this study, we used 18 F-FDG PET/CT scan whole body survey for detection of hidden infection, in patients on dialysis, labelled as FUO. In this retrospective study, 20 patients of end stage renal disease on dialysis were investigated for the cause of FUO using 18F-FDG PET/CT scan. All these patients satisfied the definition of FUO as defined by Petersdorf and Beeson. Any focal abnormal site of increased FDG concentration detected by PET/CT, either a solitary or multiple lesions was documented and at least one of the detected abnormal sites of radio tracer concentration was further examined for histopathology. All patients were on renal replacement therapy. Of these, 18 were on hemodialysis and two were on peritoneal dialysis. 18F-FDG PET/CT scan showed metabolically active lesions in 15 patients and metabolically quiescent in five patients. After 18F-FDG PET/CT scan all, but one patient had a change in treatment for fever. Anti-tuberculous treatment was given in 15 patients, antibiotics in four patients and anti-malaria treatment in one patient. The present study is first study of 18F-FDG PET/CT scan in patients of end stage renal disease on dialysis with FUO. The study showed that the 18 F FDG PET/CT scan may present an opportunity to attain the diagnosis in end stage renal disease patients on dialysis with FUO. © 2016 International Society for Hemodialysis.

  6. Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates.

    PubMed

    Li, Songye; Cai, Zhengxin; Zheng, Ming-Qiang; Holden, Daniel; Naganawa, Mika; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Kapinos, Michael; Lara-Jaime, Teresa; Navarro, Antonio; Huang, Yiyun

    2018-01-01

    The κ-opioid receptor (KOR) has been implicated in depression, addictions, and other central nervous system disorders and, thus, is an important target for drug development. We previously developed several 11 C-labeled PET radiotracers for KOR imaging in humans. Here we report the synthesis and evaluation of 18 F-LY2459989 as the first 18 F-labeled KOR antagonist radiotracer in nonhuman primates and its comparison with 11 C-LY2459989. Methods: The novel radioligand 18 F-LY2459989 was synthesized by 18 F displacement of a nitro group or an iodonium ylide. PET scans in rhesus monkeys were obtained on a small-animal scanner to assess the pharmacokinetic and in vivo binding properties of the ligand. Metabolite-corrected arterial activity curves were measured and used as input functions in the analysis of brain time-activity curves and the calculation of binding parameters. Results: With the iodonium ylide precursor, 18 F-LY2459989 was prepared at high radiochemical yield (36% ± 7% [mean ± SD]), radiochemical purity (>99%), and mean molar activity (1,175 GBq/μmol; n = 6). In monkeys, 18 F-LY2459989 was metabolized at a moderate rate, with a parent fraction of approximately 35% at 30 min after injection. Fast and reversible kinetics were observed, with a regional peak uptake time of less than 20 min. Pretreatment with the selective KOR antagonist LY2456302 (0.1 mg/kg) decreased the activity level in regions with high levels of binding to that in the cerebellum, thus demonstrating the binding specificity and selectivity of 18 F-LY2459989 in vivo. Regional time-activity curves were well fitted by the multilinear analysis 1 kinetic model to derive reliable estimates of regional distribution volumes. With the cerebellum as the reference region, regional binding potentials were calculated and ranked as follows: cingulate cortex > insula > caudate/putamen > frontal cortex > temporal cortex > thalamus, consistent with the reported KOR distribution in the monkey brain

  7. The diagnostic performance and added value of (18)F-FDG PET/CT in the detection of liver metastases in recurrent colorectal carcinoma patients.

    PubMed

    Odalovic, Strahinja; Artiko, Vera; Sobic-Saranovic, Dragana; Stojiljkovic, Milica; Petrovic, Milorad; Petrovic, Nebojsa; Kozarevic, Nebojsa; Grozdic-Milojevic, Isidora; Obradovic, Vladimir

    2015-01-01

    The aim of this study was to assess the value of (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT in detection of liver metastases in patients with suspected recurrent colorectal carcinoma, as well as to compare diagnostic performance of (18)F-FDG PET/CT with conventional imaging methods (MDCT). This study included 73 patients with resected primary colorectal adenocarcinoma referred for (18)F-FDG PET/CT to the National PET Center, at the Clinical Center of Serbia, Belgrade, from January 2010 to May 2013, with suspicion of recurrence. The patients underwent (18)F-FDG PET/CT examination on a 64-slice hybrid PET/CT scanner (Biograph, TruePoint64, Siemens Medical Solutions, Inc. USA). Prior to (18)F-FDG PET/CT all patients underwent contrast-enhanced MDCT. Findings of (18)F-FDG PET/CT and MDCT were compared to findings of subsequent histopathological examinations or with results of clinical and imaging follow-up over at least six months. Final diagnosis of liver metastases of colorectal cancer was made either by histopathological examination of specimen after biopsy or surgery, or based on clinical, laboratory and imaging evaluation during first six months after PET/CT scan. In detection of liver metastases (18)F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 83.3%, 95.3%, 92.6%, 89.1% and 90.4%, respectively. In addition, MDCT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy in detection of liver metastases of 60%, 88.4%, 78.3%, 76% and 76.7%, respectively. There was significant difference in sensitivity (83.3% vs 60%; P=0.045) between these two methods. In addition, significant difference was observed in accuracy between PET/CT and MDCT (90.4% vs 76.7%; P=0.016). The higher specificity in visualization of liver metastases was also achieved by (18)F-FDG PET/CT compared to MDCT (95.3% vs 88.4%), but this difference was not significant (P=0.37). (18)F-FDG PET

  8. Using CT Data to Improve the Quantitative Analysis of 18F-FBB PET Neuroimages

    PubMed Central

    Segovia, Fermín; Sánchez-Vañó, Raquel; Górriz, Juan M.; Ramírez, Javier; Sopena-Novales, Pablo; Testart Dardel, Nathalie; Rodríguez-Fernández, Antonio; Gómez-Río, Manuel

    2018-01-01

    18F-FBB PET is a neuroimaging modality that is been increasingly used to assess brain amyloid deposits in potential patients with Alzheimer's disease (AD). In this work, we analyze the usefulness of these data to distinguish between AD and non-AD patients. A dataset with 18F-FBB PET brain images from 94 subjects diagnosed with AD and other disorders was evaluated by means of multiple analyses based on t-test, ANOVA, Fisher Discriminant Analysis and Support Vector Machine (SVM) classification. In addition, we propose to calculate amyloid standardized uptake values (SUVs) using only gray-matter voxels, which can be estimated using Computed Tomography (CT) images. This approach allows assessing potential brain amyloid deposits along with the gray matter loss and takes advantage of the structural information provided by most of the scanners used for PET examination, which allow simultaneous PET and CT data acquisition. The results obtained in this work suggest that SUVs calculated according to the proposed method allow AD and non-AD subjects to be more accurately differentiated than using SUVs calculated with standard approaches. PMID:29930505

  9. [18F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model.

    PubMed

    Diocou, S; Volpe, A; Jauregui-Osoro, M; Boudjemeline, M; Chuamsaamarkkee, K; Man, F; Blower, P J; Ng, T; Mullen, G E D; Fruhwirth, G O

    2017-04-19

    Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [ 18 F]tetrafluoroborate ([ 18 F]BF 4 - ) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [ 18 F]BF 4 - (PET/CT) was compared to the conventional tracer [ 123 I]iodide (sequential SPECT/CT). We found that [ 18 F]BF 4 - was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [ 18 F]BF 4 - -PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [ 18 F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [ 18 F]BF 4 - -PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest.

  10. Whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) vs choline-positron emission tomography-computed tomography (choline-PET/CT) for selecting treatments in recurrent prostate cancer.

    PubMed

    Conde-Moreno, A J; Herrando-Parreño, G; Muelas-Soria, R; Ferrer-Rebolleda, J; Broseta-Torres, R; Cozar-Santiago, M P; García-Piñón, F; Ferrer-Albiach, C

    2017-05-01

    To determine the effectiveness of whole-body diffusion-weighted magnetic resonance imaging (WB-DW-MRI) in detecting metastases by comparing the results with those from choline-positron emission tomography-computed tomography (choline-PET/CT) in patients with biochemical relapse after primary treatment, and no metastases in bone scintigraphy, CT and/or pelvic MRI, or metastatic/oligometastatic prostate cancer (PCa). Patients with this disease profile who could benefit from treatment with stereotactic body radiation therapy (SBRT) were selected and their responses to these techniques were rated. This was a prospective, controlled, unicentric study, involving 46 consecutive patients from our centre who presented biochemical relapse after adjuvant, salvage or radical treatment with external beam radiotherapy, or brachytherapy. After initial tests (bone scintigraphy, CT, pelvic MRI), 35 patients with oligometastases or without them were selected. 11 patients with multiple metastases were excluded from the study. WB-DW-MRI and choline-PET/CT was then performed on each patient within 1 week. The results were interpreted by specialists in nuclear medicine and MRI. If they were candidates for treatment with ablative SBRT (SABR), they were then evaluated every three months with both tests. Choline-PET/CT detected lesions in 16 patients that were not observable using WB-DW-MRI. The results were consistent in seven patients and in three cases, a lesion was observed using WB-DW-MRI that was not detected with choline-PET/CT. The Kappa value obtained was 0.133 (p = 0.089); the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of WB-DW-MRI were estimated at 44.93, 64.29, 86.11, and 19.15%, respectively. For choline-PET/CT patients, the sensitivity, specificity, PPV, and NPV were 97.10, 58.33, 93.06, and 77.78%, respectively. Choline-PET/CT has a high global sensitivity while WB-DW-MRI has a high specificity, and so they are

  11. [(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.

    PubMed

    Bascuñana, Pablo; Javela, Julián; Delgado, Mercedes; Fernández de la Rosa, Rubén; Shiha, Ahmed Anis; García-García, Luis; Pozo, Miguel Ángel

    2016-10-01

    Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

  12. Differentiation and diagnosis of benign and malignant testicular lesions using 18F-FDG PET/CT.

    PubMed

    Shao, Dan; Gao, Qiang; Tian, Xu-Wei; Wang, Si-Yun; Liang, Chang-Hong; Wang, Shu-Xia

    2017-08-01

    The purpose of this study was to evaluate the differential diagnostic value of 18 F-fluorodeoxy glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for benign and malignant testicular lesions. The PET/CT scans of 53 patients with testicular lesions confirmed by biopsy or surgical pathology were retrospectively analyzed. There were 32 cases of malignant tumors and 21 cases of benign lesions. Differences in the maximum standardized uptake value (SUVmax) measurements and the SUVmax lesion/background ratios between benign and malignant lesions were analyzed. The diagnostic value of this PET/CT modality for the differential diagnosis of benign versus malignant testicular lesions was calculated. The differences in the SUVmax measurements and the SUVmax lesion/background ratios between benign and malignant lesions were statistically significant (SUVmax: Z=-4.295, p=0.000; SUVmax lesion/background ratio: Z=-5.219, p=0.000); specifically, both of these indicators were higher in malignant lesions compared to benign lesions. An SUVmax of 3.75 was the optimal cutoff value to differentiate between benign and malignant testicular lesions. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this PET/CT modality in the differential diagnosis of benign versus malignant testicular lesions were 90.6%, 80.9%, 86.8%, 87.9%, and 85.0%, respectively. 18 F-FDG PET/CT can accurately identify benign and malignant testicular lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.

    PubMed

    Schwartz, Jazmin; Grkovski, Milan; Rimner, Andreas; Schöder, Heiko; Zanzonico, Pat B; Carlin, Sean D; Staton, Kevin D; Humm, John L; Nehmeh, Sadek A

    2017-06-01

    Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18 F-fluoromisonidazole ( 18 F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18 F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18 F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18 F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18 F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate ( k 3 ) and delivery rate ( K 1 ), influx rate ( K i ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k 3 and K i had a significant strong correlation for all tissue types. The TBR- k 3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K 1 - k 3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both

  14. Role of (18)F-FDG PET-CT in Monitoring the Cyclophosphamide Induced Pulmonary Toxicity in Patients with Breast Cancer - 2 Case Reports.

    PubMed

    Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar

    2016-09-01

    Drug induced pulmonary toxicity is not uncommon with the use of various chemotherapeutic agents. Cyclophosphamide is a widely used chemotherapeutic drug in the treatment of breast cancer. Although rare, lung toxicity has been reported with cyclophosphamide use. Detection of bleomycin induced pulmonary toxicity and pattern of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of (18)F-FDG PET-CT in monitoring drug induced pulmonary toxicity in breast cancer. We here present two cases of cyclophosphamide induced drug toxicity. Interim (18)F-FDG PET-CT demonstrated diffusely increased tracer uptake in bilateral lung fields in both these patients. Subsequently there was resolution of lung uptake on (18)F-FDG PET-CT scan post completion of chemotherapy. These patients did not develop significant respiratory symptoms during chemotherapy treatment and in follow up.

  15. Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

    PubMed

    Tang, Caihua; Nie, Dahong; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Tang, Xiaolan

    2017-07-01

    Several 11 C and 18 F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18 F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18 F-labeled l-DOPA analogue, N-(2-[ 18 F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([ 18 F]FPDOPA) for tumor PET imaging are performed. The synthesis of [ 18 F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NFP). The biodistribution of [ 18 F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [ 18 F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. [ 18 F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [ 18 F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na + -independent system L, with Na + -dependent system B 0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [ 18 F]FPDOPA. PET imaging demonstrated intense accumulation of [ 18 F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. A novel N-substituted 18 F-labeled L-DOPA analogue [ 18 F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [ 18 F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F

  16. Comparative evaluation of 18F-FLT and 18F-FDG for detecting cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis.

    PubMed

    Norikane, Takashi; Yamamoto, Yuka; Maeda, Yukito; Noma, Takahisa; Dobashi, Hiroaki; Nishiyama, Yoshihiro

    2017-08-29

    18 F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using 18 F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to 18 F-FDG, 18 F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of 18 F-FLT and 18 F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. 18 F-FLT and 18 F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before 18 F-FDG PET/CT but were given no special dietary instructions regarding the period before 18 F-FLT PET/CT. Uptake of 18 F-FLT and 18 F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 18 F-FDG scans were rated as inconclusive because the 18 F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of 18 F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for 18 F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean 18 F-FDG SUVmax was significantly higher than the mean 18 F-FLT SUVmax (P < 0.005). Both 18 F-FDG and 18 F-FLT PET/CT studies detected all 24 extra-cardiac lesions. Using semiquantitative analysis of extra-cardiac sarcoidosis, the mean 18

  17. Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

    PubMed

    Madsen, Karine; Hesby, Sara; Poulsen, Ingrid; Fuglsang, Stefan; Graff, Jesper; Larsen, Karen B; Kammersgaard, Lars P; Law, Ian; Siebner, Hartwig R

    2017-11-01

    Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [ 18 F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [ 18 F]FDG-PET scan and venous blood sampling. Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. Our study demonstrates that the analysis method of the [ 18 F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. We recommend supplementing a static [ 18 F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Comparison study of [18F]FAl-NOTA-PRGD2, [18F]FPPRGD2, and [68Ga]Ga-NOTA-PRGD2 for PET imaging of U87MG tumors in mice.

    PubMed

    Lang, Lixin; Li, Weihua; Guo, Ning; Ma, Ying; Zhu, Lei; Kiesewetter, Dale O; Shen, Baozhong; Niu, Gang; Chen, Xiaoyuan

    2011-12-21

    [(18)F]FPPRGD2, an F-18 labeled dimeric cyclic RGDyK peptide, has favorable properties for PET imaging of angiogenesis by targeting the α(v)β(3) integrin receptor. This radiotracer has been approved by the FDA for use in clinical trials. However, the time-consuming multiple-step synthetic procedure required for its preparation may hinder the widespread usage of this tracer. The recent development of a method using an F-18 fluoride-aluminum complex to radiolabel peptides provides a strategy for simplifying the labeling procedure. On the other hand, the easy-to-prepare [(68)Ga]-labeled NOTA-RGD derivatives have also been reported to have promising properties for imaging α(v)β(3) integrin receptors. The purpose of this study was to prepare [(18)F]FPPRGD2 [corrected] , [(18)F]FAl-NOTA-PRGD2, and [(68)Ga]Ga-NOTA-PRGD2 and to compare their pharmacokinetics and tumor imaging properties using small animal PET. All three compounds showed rapid and high tracer uptake in U87MG tumors with high target-to-background ratios. The uptake in the liver, kidneys, and muscle were similar for all three tracers, and they all showed predominant renal clearance. In conclusion, [(18)F]FAl-NOTA-PRGD2 and [(68)Ga]Ga-NOTA-PRGD2 have imaging properties and pharmacokinetics comparable to those of [(18)F]FPPRGD2. Considering their ease of preparation and good imaging qualities, [(18)F]FAl-NOTA-PRGD2 and [(68)Ga]NOTA-PRGD2 are promising alternatives to [(18)F]FPPRGD2 for PET imaging of tumor α(v)β(3) integrin expression.

  19. Comparison of 68Ga-PSMA-11 and 18F-Fluciclovine PET/CT in a Case Series of 10 Patients with Prostate Cancer Recurrence.

    PubMed

    Calais, Jeremie; Fendler, Wolfgang P; Herrmann, Ken; Eiber, Matthias; Ceci, Francesco

    2018-05-01

    This was a head-to-head comparison between 68 Ga-labeled prostate-specific membrane antigen (PSMA)-11 and 18 F-fluciclovine PET/CT in a series of 10 patients with prostate cancer (PCa) recurrence. Methods: In total, 288 patients with PCa recurrence were enrolled in a prospective study of 68 Ga-PSMA-11 PET/CT imaging for recurrent disease localization (ClinicalTrials.gov identifier NCT02940262). We retrospectively identified 10 patients who underwent clinically indicated 18 F-fluciclovine PET/CT prior to enrollment. Results: The median time between the 2 scans was 2.2 mo (range, 0.2-4.2 mo). The median prostate-specific antigen (PSA) value was 1.0 ng/mL (mean, 4.7 ng/mL; range, 0.13-18.1 ng/mL) and 1.1 ng/mL (mean, 6.2 ng/mL; range, 0.24-31.3 ng/mL) at the time of 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, respectively. Five of 10 patients (50%) were negative with 18 F-fluciclovine but positive with 68 Ga-PSMA-11 PET/CT. Two of 10 patients (20%) were positive with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT, but 68 Ga-PSMA-11 PET/CT showed additional lymph nodes metastasis. Three of 10 patients (30%) were negative with both 18 F-fluciclovine and 68 Ga-PSMA-11 PET/CT. Conclusion: This case series suggests improved detection rates for 68 Ga-PSMA-11 PET/CT when compared with 18 F-fluciclovine PET/CT in patients with recurrent PCa. Prospective trials designed to directly compare the two should be initiated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  20. Optimization of the reference region method for dual pharmacokinetic modeling using Gd-DTPA/MRI and (18) F-FDG/PET.

    PubMed

    Poulin, Éric; Lebel, Réjean; Croteau, Étienne; Blanchette, Marie; Tremblay, Luc; Lecomte, Roger; Bentourkia, M'hamed; Lepage, Martin

    2015-02-01

    The combination of MRI and positron emission tomography (PET) offers new possibilities for the development of novel methodologies. In pharmacokinetic image analysis, the blood concentration of the imaging compound as a function of time, [i.e., the arterial input function (AIF)] is required for MRI and PET. In this study, we tested whether an AIF extracted from a reference region (RR) in MRI can be used as a surrogate for the manually sampled (18) F-FDG AIF for pharmacokinetic modeling. An MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and a radiotracer, (18) F-fluorodeoxyglucose ((18) F-FDG), were simultaneously injected in a F98 glioblastoma rat model. A correction to the RR AIF for Gd-DTPA is proposed to adequately represent the manually sampled AIF. A previously published conversion method was applied to convert this AIF into a (18) F-FDG AIF. The tumor metabolic rate of glucose (TMRGlc) calculated with the manually sampled (18) F-FDG AIF, the (18) F-FDG AIF converted from the RR AIF and the (18) F-FDG AIF converted from the corrected RR AIF were found not statistically different (P>0.05). An AIF derived from an RR in MRI can be accurately converted into a (18) F-FDG AIF and used in PET pharmacokinetic modeling. © 2014 Wiley Periodicals, Inc.

  1. Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles.

    PubMed

    Hostetler, Eric D; Walji, Abbas M; Zeng, Zhizhen; Miller, Patricia; Bennacef, Idriss; Salinas, Cristian; Connolly, Brett; Gantert, Liza; Haley, Hyking; Holahan, Marie; Purcell, Mona; Riffel, Kerry; Lohith, Talakad G; Coleman, Paul; Soriano, Aileen; Ogawa, Aimie; Xu, Serena; Zhang, Xiaoping; Joshi, Elizabeth; Della Rocca, Joseph; Hesk, David; Schenk, David J; Evelhoch, Jeffrey L

    2016-10-01

    A PET tracer is desired to help guide the discovery and development of disease-modifying therapeutics for neurodegenerative diseases characterized by neurofibrillary tangles (NFTs), the predominant tau pathology in Alzheimer disease (AD). We describe the preclinical characterization of the NFT PET tracer 18 F-MK-6240. In vitro binding studies were conducted with 3 H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs. Immunohistochemistry for phosphorylated tau was performed on human brain slices for comparison with 3 H-MK-6240 binding patterns on adjacent brain slices. PET studies were performed with 18 F-MK-6240 in monkeys to evaluate tracer kinetics and distribution in the brain. 18 F-MK-6240 monkey PET studies were conducted after dosing with unlabeled MK-6240 to evaluate tracer binding selectivity in vivo. The 3 H-MK-6240 binding pattern was consistent with the distribution of phosphorylated tau in human AD brain slices. 3 H-MK-6240 bound with high affinity to human AD brain cortex homogenates containing abundant NFTs but bound poorly to amyloid plaque-rich, NFT-poor AD brain homogenates. 3 H-MK-6240 showed no displaceable binding in the subcortical regions of human AD brain slices and in the hippocampus/entorhinal cortex of non-AD human brain homogenates. In monkey PET studies, 18 F-MK-6240 displayed rapid and homogeneous distribution in the brain. The 18 F-MK-6240 volume of distribution stabilized rapidly, indicating favorable tracer kinetics. No displaceable binding was observed in self-block studies in rhesus monkeys, which do not natively express NFTs. Moderate defluorination was observed as skull uptake. 18 F-MK-6240 is a promising PET tracer for the in vivo quantification of NFTs in AD patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  2. Equilibrium modeling of 5-HT(2A) receptors with [18F]deuteroaltanserin and PET: feasibility of a constant infusion paradigm.

    PubMed

    van Dyck, C H; Soares, J C; Tan, P Z; Staley, J K; Baldwin, R M; Amici, L A; Fu, X; Garg, P K; Seibyl, J P; Charney, D S; Innis, R B

    2000-11-01

    [(18)F]Altanserin has emerged as a promising positron emission tomography (PET) ligand for serotonin-2A (5-HT(2A)) receptors. The deuterium substitution of both of the 2'-hydrogens of altanserin ([(18)F]deuteroaltanserin) yields a metabolically more stable radiotracer with higher ratios of parent tracer to radiometabolites and increased specific brain uptake than [(18)F]altanserin. The slower metabolism of the deuterated analog might preclude the possibility of achieving stable plasma and brain activities with a bolus plus constant infusion within a reasonable time frame for an (18)F-labeled tracer (T(1/2) 110 min). Thus, the purpose of this study was to test the feasibility in human subjects of a constant infusion paradigm for equilibrium modeling of [(18)F]deuteroaltanserin with PET. Seven healthy male subjects were injected with [(18)F]deuteroaltanserin as a bolus plus constant infusion lasting 10 h postinjection. PET acquisitions and venous blood sampling were performed throughout the infusion period. Linear regression analysis revealed that time-activity curves for both specific brain uptake and plasma [(18)F]deuteroaltanserin concentration stabilized after about 5 h. This permitted equilibrium modeling and estimation of V(')(3) (ratio of specific uptake to total plasma parent concentration) and the binding potential V(3) (ratio of specific uptake to free plasma parent concentration). Cortical/cerebellar ratios were increased by 26% relative to those we previously observed with [(18)F]altanserin using similar methodology in a somewhat older subject sample. These results demonstrate feasibility of equilibrium imaging with [(18)F]deuteroaltanserin and suggest that it may be superior to [(18)F]altanserin as a PET radioligand.

  3. PET/CT in giant cell arteritis: High 18F-FDG uptake in the temporal, occipital and vertebral arteries.

    PubMed

    Rehak, Z; Vasina, J; Ptacek, J; Kazda, T; Fojtik, Z; Nemec, P

    18 F-FDG PET/CT imaging is useful in patients with fever of unknown origin and can detect giant cell arteritis in extracranial large arteries. However, it is usually assumed that temporal arteries cannot be visualized with a PET/CT scanner due to their small diameter. Three patients with clinical symptoms of temporal arteritis were examined using a standard whole body PET/CT protocol (skull base - mid thighs) followed by a head PET/CT scan using the brain protocol. High 18 F-FDG uptake in the aorta and some arterial branches were detected in all 3 patients with the whole body protocol. Using the brain protocol, head imaging led to detection of high 18 F-FDG uptake in temporal arteries as well as in their branches (3 patients), in occipital arteries (2 patients) and also in vertebral arteries (3 patients). Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  4. Imaging of adrenal incidentalomas with PET using (11)C-metomidate and (18)F-FDG.

    PubMed

    Minn, Heikki; Salonen, Anna; Friberg, Johan; Roivainen, Anne; Viljanen, Tapio; Långsjö, Jaakko; Salmi, Jorma; Välimäki, Matti; Någren, Kjell; Nuutila, Pirjo

    2004-06-01

    Our aim was to evaluate the use of PET with (11)C-metomidate and (18)F-FDG for the diagnosis of adrenal incidentalomas. Twenty-one patients underwent hormonal screening before dynamic imaging of the upper abdomen with (11)C-metomidate, and for 19 of these 21 patients, static (18)F-FDG imaging followed. Uptake of (11)C-metomidate and (18)F-FDG in incidentalomas was quantified and correlated with the hormonal work-up and the mass size on CT (median, 2.5 cm; range, 2-10 cm). The final diagnoses were hormonally active adenoma (n = 7), nonsecretory adenoma (n = 5), adrenocortical carcinoma (n = 1), pheochromocytoma (n = 2), benign noncortical tumor (n = 2), normal adrenal (n = 1), and malignant noncortical tumor (n = 3). Diagnosis was established at surgery (n = 9), percutaneous biopsy (n = 4), or follow-up (n = 8). The highest uptake of (11)C-metomidate, expressed as standardized uptake value (SUV), was found in adrenocortical carcinoma (SUV = 28.0), followed by active adenomas (median SUV = 12.7), nonsecretory adenomas (median SUV = 12.2), and noncortical tumors (median SUV = 5.7). Patients with adenomas had significantly higher tumor-to-normal-adrenal (11)C-metomidate SUV ratios than did patients with noncortical tumors. (18)F-FDG detected 2 of 3 noncortical malignancies but failed to detect adrenal metastases from renal cell carcinoma. All inactive and most active adenomas were difficult to detect with (18)F-FDG against background activity, whereas both pheochromocytomas and adrenocortical carcinoma showed slightly increased uptake of (18)F-FDG. There was no correlation between uptake of (11)C-metomidate or (18)F-FDG and mass size. (11)C-Metomidate is a promising PET tracer to identify incidentalomas of adrenocortical origin. (18)F-FDG should be reserved for patients with a moderate to high likelihood of neoplastic disease.

  5. Extramedullary Solitary Plasmacytoma: Demonstrating the Role of 18F-FDG PET Imaging

    PubMed Central

    Gautam, Archana; Sahu, Kamal Kant; Alamgir, Ahsan; Siddiqi, Imran

    2017-01-01

    An Extramedullary Plasmacytoma (EMP) is characterized by a neoplastic proliferation of clonal plasma cells outside the medullary cavity. EMPs are a rare occurrence compared to other malignant plasma cell disorders and account for approximately 3-5% of plasma-cell neoplasms. Although most cases of EMP are not immediately life threatening at diagnosis, EMPs can progress to Multiple Myeloma (MM) and thus, warrant monitoring. Currently, there are no standard guidelines for when and how to monitor patients who are diagnosed with or treated for a solitary plasmacytoma. We present a case of solitary EMP who was treated adequately and definitively but developed a distinct, non-contiguous subsequent solitary EMP and was only discovered due to surveillance 18F-Fludeoxyglucose Positron Emission Tomography (18F-FDG) (PET) scan. Uniform surveillance guidelines should be developed and the potential benefits of PET and other imaging techniques as well as their cost should be considered. PMID:28571247

  6. Metabolic liver function measured in vivo by dynamic (18)F-FDGal PET/CT without arterial blood sampling.

    PubMed

    Horsager, Jacob; Munk, Ole Lajord; Sørensen, Michael

    2015-01-01

    Metabolic liver function can be measured by dynamic PET/CT with the radio-labelled galactose-analogue 2-[(18)F]fluoro-2-deoxy-D-galactose ((18)F-FDGal) in terms of hepatic systemic clearance of (18)F-FDGal (K, ml blood/ml liver tissue/min). The method requires arterial blood sampling from a radial artery (arterial input function), and the aim of this study was to develop a method for extracting an image-derived, non-invasive input function from a volume of interest (VOI). Dynamic (18)F-FDGal PET/CT data from 16 subjects without liver disease (healthy subjects) and 16 patients with liver cirrhosis were included in the study. Five different input VOIs were tested: four in the abdominal aorta and one in the left ventricle of the heart. Arterial input function from manual blood sampling was available for all subjects. K*-values were calculated using time-activity curves (TACs) from each VOI as input and compared to the K-value calculated using arterial blood samples as input. Each input VOI was tested on PET data reconstructed with and without resolution modelling. All five image-derived input VOIs yielded K*-values that correlated significantly with K calculated using arterial blood samples. Furthermore, TACs from two different VOIs yielded K*-values that did not statistically deviate from K calculated using arterial blood samples. A semicircle drawn in the posterior part of the abdominal aorta was the only VOI that was successful for both healthy subjects and patients as well as for PET data reconstructed with and without resolution modelling. Metabolic liver function using (18)F-FDGal PET/CT can be measured without arterial blood samples by using input data from a semicircle VOI drawn in the posterior part of the abdominal aorta.

  7. Radiation dosimetry estimates of (18)F-alfatide II based on whole-body PET imaging of mice.

    PubMed

    Wang, Si-Yang; Bao, Xiao; Wang, Ming-Wei; Zhang, Yong-Ping; Zhang, Ying-Jian; Zhang, Jian-Ping

    2015-11-01

    We estimated the dosimetry of (18)F-alfatide II with the method established by MIRD based on biodistribution data of mice. Six mice (three females and three males) were scanned for 160min on an Inveon MicroPET/CT scanner after injection of (18)F-alfatide II via tail vein. Eight source organs were delineated on the CT images and their residence times calculated. The data was then converted to human using scaling factors based on organ and body weight. The absorbed doses for human and the resulting effective dose were computed by OLINDA 1.1 software. The highest absorbed doses was observed in urinary bladder wall (male 0.102mGy/MBq, female 0.147mGy/MBq); and the lowest one was detected in brain (male 0.0030mGy/MBq, female 0.0036). The total effective doses were 0.0127mSv/MBq for male and 0.0166 mSv/MBq for female, respectively. A 370-MBq injection of (18)F-alfatide II led to an estimated effective dose of 4.70mSv for male and 6.14mSv for female. The potential radiation burden associated with (18)F-alfatide II/PET imaging therefore is comparable to other PET examinations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Inter- and Intraobserver Agreement of 18F-FDG PET/CT Image Interpretation in Patients Referred for Assessment of Cardiac Sarcoidosis.

    PubMed

    Ohira, Hiroshi; Ardle, Brian Mc; deKemp, Robert A; Nery, Pablo; Juneau, Daniel; Renaud, Jennifer M; Klein, Ran; Clarkin, Owen; MacDonald, Karen; Leung, Eugene; Nair, Girish; Beanlands, Rob; Birnie, David

    2017-08-01

    Recent studies have reported the usefulness of 18 F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18 F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18 F-FDG PET/CT images. 18 F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18 F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18 F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18 F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion : The interobserver agreement of cardiac 18 F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary

  9. Different predictive values of interim 18F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma.

    PubMed

    Kim, Jihyun; Lee, Jeong-Ok; Paik, Jin Ho; Lee, Won Woo; Kim, Sang Eun; Song, Yoo Sung

    2017-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of 18 F-fluoro-2-dexoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim 18 F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim 18 F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling. We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim 18 F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans' algorithm. In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim 18 F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim 18 F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in non-GCB subtype of DLBCL. Interim 18 F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for

  10. Hybrid core shell nanoparticles entrapping Gd-DTPA and 18F-FDG for simultaneous PET/MRI acquisitions.

    PubMed

    Vecchione, Donatella; Aiello, Marco; Cavaliere, Carlo; Nicolai, Emanuele; Netti, Paolo Antonio; Torino, Enza

    2017-09-01

    Although there has been an improvement in the hardware and software of the PET/MRI system, the development of the nanoprobes exploiting the simultaneous acquisition of the bimodal data is still under investigation. Moreover, few studies on biocompatible and clinically relevant probes are available. This work presents a core-shell polymeric nanocarrier with improved relaxometric properties for simultaneous PET/MRI acquisitions. Core-shell nanoparticles entrapping the Gd-DTPA and 18 F-FDG are obtained by a complex coacervation. The boosting of r 1 of the entrapped Gd-DTPA up to five-times compared with 'free Gd-DTPA', is confirmed by the PET/MRI scan. The sorption of 18 F-FDG into the nanoparticles is studied and designed to be integrated downstream for the production of the tracer.

  11. Localization and prediction of malignant potential in recurrent pheochromocytoma/paraganglioma (PCC/PGL) using 18F-FDG PET/CT.

    PubMed

    Fikri, Ahmad Saad Fathinul; Kroiss, A; Ahmad, A Z F; Zanariah, H; Lau, W F E; Uprimny, C; Donnemiller, E; Kendler, D; Nordin, A J; Virgolini, I J

    2014-06-01

    To our knowledge, data are lacking on the role of 18F-FDG PET/CT in the localization and prediction of neuroendocrine tumors, in particular the pheochromocytoma/paraganglioma (PCC/PGL) group. To evaluate the role of 18F-FDG PET/CT in localizing and predicting the malignant potential of PCC/PGL. Twenty-three consecutive patients with a history of PCC/PGL, presenting with symptoms related to catecholamine excess, underwent 18F-FDG PET/CT. Final confirmation of the diagnosis was made using the composite references. PET/CT findings were analyzed on a per-lesion basis and a per-patient basis. Tumor SUVmax was analyzed to predict the dichotomization of patient endpoints for the local disease and metastatic groups. We investigated 23 patients (10 men, 13 women) with a mean age of 46.43 ± 3.70 years. Serum catecholamine levels were elevated in 82.60% of these patients. There were 136 sites (mean SUVmax: 16.39 ± 3.47) of validated disease recurrence. The overall sensitivities for diagnostic CT, FDG PET, and FDG PET/CT were 86.02%, 87.50%, and 98.59%, respectively. Based on the composite references, 39.10% of patients had local disease. There were significant differences in the SUVmax distribution between the local disease and metastatic groups; a significant correlation was noted when a SUVmax cut-off was set at 9.2 (P<0.05). In recurrent PCC/PGL, diagnostic 18F-FDG PET/CT is a superior tool in the localization of recurrent tumors. Tumor SUVmax is a potentially useful predictor of malignant tumor potential. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

    PubMed

    Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

    2016-01-01

    We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  13. Fat-constrained 18F-FDG PET reconstruction using Dixon MR imaging and the origin ensemble algorithm

    NASA Astrophysics Data System (ADS)

    Wülker, Christian; Heinzer, Susanne; Börnert, Peter; Renisch, Steffen; Prevrhal, Sven

    2015-03-01

    Combined PET/MR imaging allows to incorporate the high-resolution anatomical information delivered by MRI into the PET reconstruction algorithm for improvement of PET accuracy beyond standard corrections. We used the working hypothesis that glucose uptake in adipose tissue is low. Thus, our aim was to shift 18F-FDG PET signal into image regions with a low fat content. Dixon MR imaging can be used to generate fat-only images via the water/fat chemical shift difference. On the other hand, the Origin Ensemble (OE) algorithm, a novel Markov chain Monte Carlo method, allows to reconstruct PET data without the use of forward- and back projection operations. By adequate modifications to the Markov chain transition kernel, it is possible to include anatomical a priori knowledge into the OE algorithm. In this work, we used the OE algorithm to reconstruct PET data of a modified IEC/NEMA Body Phantom simulating body water/fat composition. Reconstruction was performed 1) natively, 2) informed with the Dixon MR fat image to down-weight 18F-FDG signal in fatty tissue compartments in favor of adjacent regions, and 3) informed with the fat image to up-weight 18F-FDG signal in fatty tissue compartments, for control purposes. Image intensity profiles confirmed the visibly improved contrast and reduced partial volume effect at water/fat interfaces. We observed a 17+/-2% increased SNR of hot lesions surrounded by fat, while image quality was almost completely retained in fat-free image regions. An additional in vivo experiment proved the applicability of the presented technique in practice, and again verified the beneficial impact of fat-constrained OE reconstruction on PET image quality.

  14. SU-C-BRA-01: 18F-NaF PET/CT-Directed Dose Escalation in Stereotactic Body Radiotherapy for Spine Oligometastases From Prostate Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, L; University of Nevada, Las Vegas, Las Vegas, NV; Zhang, W

    2015-06-15

    Purpose: To investigate the technical feasibility of SBRT dose painting using {sup 18}F-NaF positron emission tomography (PET) scans guidance in patients with spine oligometastases from prostate cancer. Methods: As a proof of concept, six patients with 14 spine oligometastatic lesions from prostate cancer who had {sup 18}F-NaF PET/CT scan prior to treatment were retrospectively included. GTV{sub reg} was delineated according to the regular tumor boundary shown on PET and/or CT images; and GTV{sub MATV} was contoured based on a net metabolically active tumor volume (MATV) defined by 60% of the SUV{sub max} values on {sup 18}F-NaF PET images. The PTVsmore » (PTV{sub reg} and PTV{sub MATV}) were defined as respective GTVs (plus involved entire vertebral body for PTV{sub reg}) with a 3-mm isotropic expansion margin. Three 1-fraction SBRT plans using VMAT technique along with 10 MV FFF beams (Plan{sub 24Gy}, Plan{sub 24–27Gy}, and Plan{sub 24–30Gy}) were generated for each patient. All plans included a dose of 24 Gy prescribed to PTV{sub reg}. The Plan{sub 24–27Gy} and Plan{sub 24–30Gy} also included a simultaneous boost dose of 27 Gy or 30 Gy prescribed to the PTV{sub MATV}, respectively. The feasibility of 18F-NaF PET-guided SBRT dose escalation was evaluated by its ability to achieve the prescription dose objectives while adhering to organ-at-risk (OAR) dose constraints. The normal tissue complication probabilities (NTCP) calculated by radiological models were also compared between the plans. Results: In all 33 SBRT plans generated, the planning objectives and dose constraints were met without exception. Plan{sub 24–27Gy} and Plan{sub 24–30Gy} had a significantly higher dose in PTV{sub MATV} than Plan{sub 24Gy} (p < 0.05), respectively, while maintaining a similar OAR sparing profile and NTCP values. Conclusion: Using VMAT with FFF beams to incorporate a simultaneous {sup 18}F-NaF PET-guided radiation boost dose up to 30 Gy into a SBRT plan is

  15. Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An (18)F-FDG-PET study.

    PubMed

    Ma, Suhua; You, Shengzhong; Hao, Li; Zhang, Dongchuan; Quan, Li

    2015-07-01

    This study was designed to evaluate changes in brain glucose metabolism in rats following ligature strangulation. Thirteen male Wistar rats were used in the present study, divided into control (n=7) and asphyxia groups (n=6, ligature strangulation). Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was used to evaluate brain glucose metabolism. Rats were scanned for PET-CT, and image data co-registered with a T2WI MRI template using SPM8 software. Image J was employed to draw regions of interest (ROIs) from the MRI template and acquire ROI activity information from the PET images. In the asphyxia group vs. controls, (18)F-FDG uptake (FU) was decreased in the substantia nigra (25.26%, p<0.001), rhombencephalon (pons/medulla oblongata, 13.92%, p<0.01), hypothalamus (22.06%, p<0.01), ventral tegmentum (10.12%, p<0.05) and amygdala (12.74%, p<0.05); however, FU was increased in motor (18.21%, p<0.05) and visual cortices (19.2%, p<0.05). The glucose metabolism distribution map in the asphyxiated rat brains were substantially changed versus controls. PET with (18)F-FDG can demonstrate excitement and inhibition of different brain areas even in cases of ligature strangulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

    PubMed

    Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

    2015-04-21

    Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

  17. In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

    PubMed Central

    Barrio, Jorge R.; Small, Gary W.; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A.; Giza, Christopher C.; Fitzsimmons, Robert P.; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. PMID:25848027

  18. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data.

    PubMed

    Fanti, Stefano; Minozzi, Silvia; Castellucci, Paolo; Balduzzi, Sara; Herrmann, Ken; Krause, Bernd Joachim; Oyen, Wim; Chiti, Arturo

    2016-01-01

    For the last decade PET and PET/CT with (11)C-choline have been proposed for the evaluation of prostate cancer (PC), but the diagnostic performance of (11)C-choline PET/CT is still a matter of debate. We performed a comprehensive review of the most important clinical application of (11)C-choline PET, restaging of patients with biochemical relapse, following a rigorous methodological approach and including assessment of the risk of bias. We conducted a systematic review and meta-analysis of the literature assessing (11)C-choline PET/CT for its accuracy in the diagnosis and ability to detect the site of recurrence of PC in the restaging of patients with biochemical recurrence after initial treatment with curative intent. We performed a comprehensive literature search of PubMed and the Cochrane Library to determine the accuracy for the detection of the site of recurrence (prostate bed recurrences, metastatic spread to locoregional pelvic lymph nodes or distant metastases). Only studies with a reference standard (for prostatic bed histopathology, for histopathology or biopsy of distant metastases or a composite reference standard with clinical follow-up of at least 12 months, correlative imaging and clinical data) were included. Overall 425 studies were retrieved, of which 43 were judged as potentially relevant and 29 with 2,686 participants were finally included. Of these 29 studies, 18 reported results for any relapse, All 18 studies, with a total of 2,126 participants, reported detection rates. The pooled rate was 62 % (95 % CI 53 - 71 %). Of the 18 studies, 12 with 1,270 participants reported useful data to derive sensitivity and specificity. The pooled sensitivity was 89 % (95 % CI 83 - 93 %) and the pooled specificity was 89 % (95 % CI 73 - 96 %). Of 11 studies reporting results for local relapse, 9 with 993 participants reported detection rates. The pooled rate was 27 % (95 % CI 16 - 38 %). Six studies with 491 participants reported

  19. Prospective comparison of 68Ga-PSMA PET/CT, 18F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer.

    PubMed

    Zacho, Helle D; Nielsen, Julie B; Afshar-Oromieh, Ali; Haberkorn, Uwe; deSouza, Nandita; De Paepe, Katja; Dettmann, Katja; Langkilde, Niels C; Haarmark, Christian; Fisker, Rune V; Arp, Dennis T; Carl, Jesper; Jensen, Jørgen B; Petersen, Lars J

    2018-06-06

    To prospectively compare diagnostic accuracies for detection of bone metastases by 68 Ga-PSMA PET/CT, 18 F-NaF PET/CT and diffusion-weighted MRI (DW 600 -MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68 Ga-PSMA PET/CT, a 18 F-NaF PET/CT and a DW 600 -MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm 2 ). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68 Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18 NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW 600 -MRI (n = 60 patients). The diagnostic performance of DW 600 -MRI was significantly lower than that of 68 Ga-PSMA PET/CT and 18 NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68 Ga-PSMA PET/CT and 18 NaF PET/CT (p = 0.65). 68 Ga-PSMA PET/CT and 18 F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW 600 -MRI, which was inadequate for diagnosing bone

  20. [18F]FDG imaging of head and neck tumours: comparison of hybrid PET and morphological methods.

    PubMed

    Dresel, S; Grammerstorff, J; Schwenzer, K; Brinkbäumer, K; Schmid, R; Pfluger, T; Hahn, K

    2003-07-01

    The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose ([(18)F]FDG) imaging of head and neck tumours using a second- or third-generation hybrid PET device. Results were compared with the findings of spiral computed tomography (CT) and magnetic resonance imaging (MRI), and, as regards lymph node metastasis, the ultrasound findings. A total of 116 patients with head and neck tumours (83 males and 33 females aged 27-88 years) were examined using a hybrid PET scanner after injection of 185-350 MBq of [(18)F]FDG (Picker Prism 2000 XP-PCD, Marconi Axis gamma-PET(2) AZ). Hybrid PET examinations were performed in list mode using an axial filter. Reconstruction of data was performed iteratively. Ninety-six patients underwent CT using a multislice technique (Siemens Somatom Plus 4, Marconi MX 8000), 18 patients underwent MRI and 100 patients were examined by ultrasound. All findings were verified by histology, which was considered the gold standard, or, in the event of negative histology, by follow-up. Correct diagnosis of the primary or recurrent lesion was made in 73 of 85 patients using the hybrid PET scanner, in 50 of 76 patients on CT and in 7 of 10 patients on MRI. Hybrid PET successfully visualised metastatic disease in cervical lymph nodes in 28 of 34 patients, while 23 of 31 were correctly diagnosed with CT, 3 of 4 with MRI and 30 of 33 with ultrasound. False positive results regarding lymph node metastasis were seen in three patients with hybrid PET, in 14 patients with CT and in 13 patients with ultrasound. MRI yielded no false positive results concerning lymph node metastasis. In one patient, unrecognised metastatic lesions were seen on hybrid PET elsewhere in the body (lung: n=1; bone: n=1). Additional malignant lesions at sites other than the head and neck tumour were found in three patients (one patient with lung cancer, one patient with pelvic metastasis due to a carcinoma of the prostate and one patient with pulmonary metastasis due to breast

  1. Methodologic Considerations for Quantitative 18F-FDG PET/CT Studies of Hepatic Glucose Metabolism in Healthy Subjects.

    PubMed

    Trägårdh, Malene; Møller, Niels; Sørensen, Michael

    2015-09-01

    PET with the glucose analog (18)F-FDG is used to measure regional tissue metabolism of glucose. However, (18)F-FDG may have affinities different from those of glucose for plasma membrane transporters and intracellular enzymes; the lumped constant (LC) can be used to correct these differences kinetically. The aims of this study were to investigate the feasibility of measuring human hepatic glucose metabolism with dynamic (18)F-FDG PET/CT and to determine an operational LC for (18)F-FDG by comparison with (3)H-glucose measurements. Eight healthy human subjects were included. In all studies, (18)F-FDG and (3)H-glucose were mixed in saline and coadministered. A 60-min dynamic PET recording of the liver was performed for 180 min with blood sampling from catheters in a hepatic vein and a radial artery (concentrations of (18)F-FDG and (3)H-glucose in blood). Hepatic blood flow was determined by indocyanine green infusion. First, 3 subjects underwent studies comparing bolus administration and constant-infusion administration of tracers during hyperinsulinemic-euglycemic clamping. Next, 5 subjects underwent studies comparing fasting and hyperinsulinemic-euglycemic clamping with tracer infusions. Splanchnic extraction fractions of (18)F-FDG (E*) and (3)H-glucose (E) were calculated from concentrations in blood, and the LC was calculated as ln(1 - E*)/ln(1 - E). Volumes of interest were drawn in the liver tissue, and hepatic metabolic clearance of (18)F-FDG (mL of blood/100 mL of liver tissue/min) was estimated. For bolus versus infusion, E* values were always negative when (18)F-FDG was administered as a bolus and were always positive when it was administered as an infusion. For fasting versus clamping, E* values were positive in 4 of 5 studies during fasting and were always positive during clamping. Negative extraction fractions were ascribed to the tracer distribution in the large volume of distribution in the prehepatic splanchnic bed. The LC ranged from 0.43 to 2

  2. 18F-FDG PET/CT as an Indicator of Survival in Ewing Sarcoma of Bone

    PubMed Central

    Salem, Usama; Amini, Behrang; Chuang, Hubert H.; Daw, Najat C.; Wei, Wei; Haygood, Tamara Miner; Madewell, John E.; Costelloe, Colleen M.

    2017-01-01

    Objective: The existing literature of 18 F-FDG PET/CT in Ewing sarcoma investigates mixed populations of patients with both soft tissue and bone primary tumors. The aim of our study was to evaluate whether the maximum standardized uptake value (SUVmax) obtained with 18F-FDG PET/CT before and after induction chemotherapy can be used as an indicator of survival in patients with Ewing sarcoma originating exclusively in the skeleton. Materials and Methods: A retrospective database search from 2004-2011 identified 28 patients who underwent 18 F-FDG PET/CT before (SUV1, n= 28) and after (SUV2, n=23) induction chemotherapy. Mean follow up was 3.3 years and median follow up for survivors was 6.3 years (range: 2.6-9.8 years). Multivariate and univariate Cox proportional hazard model was used to assess for correlation of SUV1, SUV2, and the change in SUVmax with overall survival (OS) and progression-free survival (PFS). Results: Mean SUVmax was 10.74 before (SUV1) and after 4.11 (SUV2) induction chemotherapy. High SUV1 (HR = 1.05, 95% CI: 1.0-1.1, P = 0.01) and SUV2 (HR =1.2, 95% CI: 1.0-1.4, P = 0.01) were associated with worse OS. A cut off point of 11.6 was identified for SUV1. SUV1 higher than 11.6 had significantly worse OS (HR = 5.71, 95% CI: 1.85 - 17.61, P = 0.003) and PFS (HR = 3.16, 95% CI: 1.13 - 8.79, P = 0.03, P < 0.05 is significant). Conclusion: 18F-FDG PET/CT can be used as a prognostic indicator for survival in primary Ewing sarcoma of bone. PMID:28928879

  3. Can (18)F-FDG PET/CT scan change treatment planning and be prognostic in recurrent colorectal carcinoma? A prospective and follow-up study.

    PubMed

    Artiko, Vera; Odalovic, Strahinja; Sobic-Saranovic, Dragana; Petrovic, Milorad; Stojiljkovic, Milica; Petrovic, Nebojsa; Kozarevic, Nebojsa; Grozdic-Milojevic, Isidora; Obradovic, Vladimir

    2015-01-01

    To prospectively study whether in patients with resected primary colorectal cancer fluorine- 18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) examination could diagnose the stage, specify treatment procedure and be prognostic. This prospective study included 75 patients with resected primary colorectal adenocarcinoma referred for (18)F-FDG PET/CT to the National PET Center, at the Clinical Center of Serbia, Belgrade, from January 2010 to May 2013. Findings of (18)F-FDG PET/CT were compared to findings of subsequent histopathological examinations or with results of clinical and imaging follow-up. Patients were followed after PET/CT examination for a mean follow-up time of 16.7±5.9 months. In the detection of recurrent disease (18)F-FDG PET/CT showed overall sensitivity, specificity, PPV, NPV and accuracy of 96.6%, 82.4%, 94.9%, 87.5% and 93.3%, respectively. In the detection of stages I and II sensitivity, specificity and accuracy of (18)F-FDG PET/CT were: 88%, 96.6% and 94.7%, respectively, and in the detection of stages III and IV sensitivity, specificity and accuracy were 94.9%, 87.5% and 93.3%, respectively. These findings prevented or changed intended surgical treatment in 12/32 cases. Univariate and multivariate Cox proportional regression analyses revealed that metastatic recurrence (stages III and IV) was the only and independent prognostic factor of disease progression during follow-up (P=0.012 and P=0.023, respectively). Although, survival seemed better in patients with local recurrence compared to metastatic recurrent disease, this difference did not reach significance (Log-rank test; P=0.324). In addition, progression-free survival time was significantly longer in patients in whom (18)F-FDG PET/CT scan led to treatment changes (Log-rank test; P=0.037). (18)F-FDG PET/CT was sensitive and accurate for the detection and staging of local and metastatic recurrent colorectal carcinoma, with higher specificity in the

  4. (11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients.

    PubMed

    Picchio, M; Berardi, G; Fodor, A; Busnardo, E; Crivellaro, C; Giovacchini, G; Fiorino, C; Kirienko, M; Incerti, E; Messa, C; Gianolli, L; Di Muzio, N

    2014-07-01

    To evaluate, in prostate cancer (PCa) patients the potential of (11)C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed. We enrolled 83 PCa patients (mean age 68 years, range 51 - 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 - 187.00 ng/ml; PSA0) who showed pathological findings on (11)C-choline PET/CT only at the LN site. (11)C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT0). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT0 were treated with high doses using SIB. Doses were in the range 36 - 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 - 365 days), serum PSA was measured in all patients (PSA1) and compared with PSA0 to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT1) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity. PET/CT0 revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA0, PSA1 (mean 6.28 ng/ml, range 0.00 - 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT1, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic

  5. Automated synthesis of 4-[(18)F]fluoroanisole, [(18)F]DAA1106 and 4-[(18)F]FPhe using Cu-mediated radiofluorination under "minimalist" conditions.

    PubMed

    Zischler, Johannes; Krapf, Philipp; Richarz, Raphael; Zlatopolskiy, Boris D; Neumaier, Bernd

    2016-09-01

    The application of the "minimalist" approach to Cu-mediated radiofluorination allows the efficient preparation of (18)F-labeled arenes regardless of their electronic properties. The implementation of this methodology on a commercially available synthesis module (hotbox(three), Scintomics, Germany) enabled the automated production of 4-[(18)F]fluoroanisole as well as the clinically relevant PET-tracers, 4-[(18)F]FPhe and [(18)F]DAA1106, in radiochemical yields of 41-61% and radiochemical purities of >95% within 30-60min. These results demonstrated the high efficacy and versatility of the developed method that will open up opportunities for a broad application of Cu-mediated radiofluorination in PET-chemistry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

    NASA Astrophysics Data System (ADS)

    Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

    2007-02-01

    Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PETPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

  7. The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma.

    PubMed

    Galldiks, Norbert; Stoffels, Gabriele; Filss, Christian; Rapp, Marion; Blau, Tobias; Tscherpel, Caroline; Ceccon, Garry; Dunkl, Veronika; Weinzierl, Martin; Stoffel, Michael; Sabel, Michael; Fink, Gereon R; Shah, Nadim J; Langen, Karl-Josef

    2015-09-01

    We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001). Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. The use of 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) as a non-invasive pharmacodynamic biomarker to determine the minimally pharmacologically active dose of AZD8835, a novel PI3Kα inhibitor

    PubMed Central

    Maynard, Juliana; Emmas, Sally-Ann; Ble, Francois-Xavier; Barjat, Herve; Lawrie, Emily; Hancox, Urs; Polanska, Urszula M.; Pritchard, Alison; Hudson, Kevin

    2017-01-01

    Background The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development. It has been used widely with PI3K inhibitors both clinically and pre-clinically because of the role of the PI3K pathway in glucose metabolism. In this study we investigated the potential of 18F-FDG PET as a non-invasive pharmacodynamic biomarker for AZD8835. We sought to understand if 18F-FDG PET could determine the minimally effective dose of AZD8835 and correlate with other pharmacodynamic biomarkers for validation of its use in clinical development. 18F-FDG PET scans were performed in nude mice in the BT474C breast xenograft model. Mice were fasted prior to imaging and static 18F-FDG PET was performed. Treatment groups received AZD8835 by oral gavage at a dose volume of 10ml/kg. Treatment groups received either 3, 6, 12.5, 25 or 50mg/kg AZD8835. Tumour growth was monitored throughout the study, and at the end of the imaging procedure, tumours were taken and a full pharmacodynamic analysis was performed. Results Results showed that AZD8835 reduced 18F-FDG uptake at a dose of 12.5, 25 and 50mg/kg with no significant reduction at doses of 3 and 6mg/kg. These results were consistent with other pharmacodynamics biomarkers measured and show 18F-FDG PET as a sensitive biomarker with the ability to determine the minimal effective dose of AZD8835. Conclusions Our pre-clinical studies support the use of 18F-FDG PET imaging as a sensitive and non- invasive pharmacodynamic biomarker (understanding the role of PI3K signalling in glucose uptake) for AZD8835 with

  9. MO-AB-BRA-05: [18F]NaF PET/CT Imaging Biomarkers in Metastatic Prostate Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harmon, S; Perk, T; Lin, C

    Purpose: Clinical use of {sup 18}F-Sodium Fluoride (NaF) PET/CT in metastatic settings often lacks technology to quantitatively measure full disease dynamics due to high tumor burden. This study assesses radiomics-based extraction of NaF PET/CT measures, including global metrics of overall burden and local metrics of disease heterogeneity, in metastatic prostate cancer for correlation to clinical outcomes. Methods: Fifty-six metastatic Castrate-Resistant Prostate Cancer (mCRPC) patients had NaF PET/CT scans performed at baseline and three cycles into chemotherapy (N=16) or androgen-receptor (AR) inhibitors (N=39). A novel technology, Quantitative Total Bone Imaging (QTBI), was used for analysis. Employing hybrid PET/CT segmentation and articulatedmore » skeletal-registration, QTBI allows for response assessment of individual lesions. Various SUV metrics were extracted from each lesion (iSUV). Global metrics were extracted from composite lesion-level statistics for each patient (pSUV). Proportion of detected lesions and those with significant response (%-increase or %-decrease) was calculated for each patient based on test-retest limits for iSUV metrics. Cox proportional hazard regression analyses were conducted between imaging metrics and progression-free survival (PFS). Results: Functional burden (pSUV{sub total}) assessed mid-treatment was the strongest univariate predictor of PFS (HR=2.03; p<0.0001). Various global metrics outperformed baseline clinical markers, including fraction of skeletal burden, mean uptake (pSUV{sub mean}), and heterogeneity of average lesion uptake (pSUV{sub hetero}). Of 43 patients with paired baseline/mid-treatment imaging, 40 showed heterogeneity in lesion-level response, containing populations of lesions with both increasing/decreasing metrics. Proportion of lesions with significantly increasing iSUV{sub mean} was highly predictive of clinical PFS (HR=2.0; p=0.0002). Patients exhibiting higher proportion of lesions with decreasing i

  10. PET Imaging of Fatty Acid Amide Hydrolase with [ 18F]DOPP in Nonhuman Primates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rotstein, Benjamin H.; Wey, Hsiao -Ying; Shoup, Timothy M.

    Here, the fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [ 11C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [ 18F]DOPP ([ 18F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising 18F-labeled analogue based on rodent studies. The goal of this work is to evaluate [ 18F]DOPP in nonhuman primates to support its clinical translation. High specific activity [ 18F]DOPP (5–6 Ci·μmol –1) was administered intravenously (iv) to three baboons (2M/1F, 3–4 years old). The distribution and pharmacokinetics were quantified followingmore » a 2 h dynamic imaging session using a simultaneous PET/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 μg/kg iv, 10 min prior to [ 18F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated ~95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [ 18F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [ 11C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter λk 3 was therefore used to evaluate whole brain (WB) and regional binding of [ 18F]DOPP. Pretreatment studies showed inhibition of λk 3 across all brain regions (WB baseline: 0.112 mL/cm3/min; 300 μg/kg URB597: 0.058 mL/cm 3/min), suggesting that [ 18F]DOPP binding is specific for FAAH, consistent with previous rodent data.« less

  11. PET Imaging of Fatty Acid Amide Hydrolase with [ 18F]DOPP in Nonhuman Primates

    DOE PAGES

    Rotstein, Benjamin H.; Wey, Hsiao -Ying; Shoup, Timothy M.; ...

    2014-07-08

    Here, the fatty acid amide hydrolase (FAAH) regulates endocannabinoid signaling. [ 11C]CURB, an irreversibly binding FAAH inhibitor, has been developed for clinical research imaging with PET. However, no fluorine-18 labeled radiotracer for FAAH has yet advanced to human studies. [ 18F]DOPP ([ 18F]3-(4,5-dihydrooxazol-2-yl)phenyl (5-fluoropentyl)carbamate) has been identified as a promising 18F-labeled analogue based on rodent studies. The goal of this work is to evaluate [ 18F]DOPP in nonhuman primates to support its clinical translation. High specific activity [ 18F]DOPP (5–6 Ci·μmol –1) was administered intravenously (iv) to three baboons (2M/1F, 3–4 years old). The distribution and pharmacokinetics were quantified followingmore » a 2 h dynamic imaging session using a simultaneous PET/MR scanner. Pretreatment with the FAAH-selective inhibitor, URB597, was carried out at 200 or 300 μg/kg iv, 10 min prior to [ 18F]DOPP administration. Rapid arterial blood sampling for the first 3 min was followed by interval sampling with metabolite analysis to provide a parent radiotracer plasma input function that indicated ~95% baseline metabolism at 60 min and a reduced rate of metabolism after pretreatment with URB597. Regional distribution data were analyzed with 1-, 2-, and 3-tissue compartment models (TCMs), with and without irreversible trapping since [ 18F]DOPP covalently links to the active site of FAAH. Consistent with previous findings for [ 11C]CURB, the 2TCM with irreversible binding was found to provide the best fit for modeling the data in all regions. The composite parameter λk 3 was therefore used to evaluate whole brain (WB) and regional binding of [ 18F]DOPP. Pretreatment studies showed inhibition of λk 3 across all brain regions (WB baseline: 0.112 mL/cm3/min; 300 μg/kg URB597: 0.058 mL/cm 3/min), suggesting that [ 18F]DOPP binding is specific for FAAH, consistent with previous rodent data.« less

  12. The role of PET/CT in evaluation of Facet and Disc abnormalities in patients with low back pain using (18)F-Fluoride.

    PubMed

    Gamie, Sherief; El-Maghraby, Tarek

    2008-01-01

    Bone scintigraphy including Single Photon Emission Computed Tomography (SPECT) is known for its role in the diagnosis of low back pain disorders. Positron Emission Tomography (PET) with (18)F (Flouride-18) as a tracer can be used to carry out bone scans with improved image quality. With the addition of CT, simultaneous PET/CT fused images provide more accurate anatomical details. The objectives of this work are to assess the use of (18)F-PET/CT in patients with back pain and suspected facetogenic pain, and to find the frequency of facet arthropathy versus disc disease abnormalities. 67 patients who presented with back pain underwent routine X-ray, CT and/or MRI, which failed to identify a clear cause, were referred to (18)F-PET/CT. Among the main group, a subset of 25 patients had previous spine surgery consisting of laminectomy or discectomy (17 patients) and lumbar fusion (8 patients). The PET/CT scan was acquired on a GE VCT 64-Slice combined scanner. Imaging started 45-60 minutes after administration of 12-15 mCi (444-555 MBq) of (18)F-Fluoride. The PET scan was acquired from the skull base through the inguinal region in 3D mode at 2 minutes/bed. A lowresolution, non-contrast CT scan was also acquired for anatomic localization and attenuation correction. The (18)F-PET/CT showed abnormal uptake in the spine in 56 patients, with an overall detection ability of 84%. Facet joints as a cause of back pain was much more frequent (25 with abnormal scans). One-third (36%) of the patients showed multiple positive uptake in both facet joints and disc areas (20/56). The patients were further divided into two groups. Group A consisted of 42 patients (63%) with back pain and no previous operative procedures, and the (18)F-PET/CT showed a high sensitivity (88%) in identifying the source of pain in 37/42 patients. Group B included 25 patients (37%) with prior lumbar fusion or laminectomy, in which the PET/CT showed positive uptake in 76% (19/25 patients). (18)F-PET/CT showed

  13. Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

    PubMed

    Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

    2017-12-01

    18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

  14. Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.

    PubMed

    Toyama, Hiroshi; Ichise, Masanori; Liow, Jeih-San; Modell, Kendra J; Vines, Douglass C; Esaki, Takanori; Cook, Michelle; Seidel, Jurgen; Sokoloff, Louis; Green, Michael V; Innis, Robert B

    2004-08-01

    The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states. Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers. Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to

  15. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fernandes, F; Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia; Silva, D da

    2015-06-15

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transportmore » (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga

  16. PET Imaging Evaluation of [18F]DBT-10, a Novel Radioligand Specific to α7 Nicotinic Acetylcholine Receptors, in Nonhuman Primates

    PubMed Central

    Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Scheunemann, Matthias; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Carson, Richard E.; Brust, Peter; Huang, Yiyun

    2015-01-01

    Purpose PET radioligands specific to α7 nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer’s disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α7-nAChR specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[18F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([18F]DBT-10), in nonhuman primates. Methods [18F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [18F]DBT-10 PET, with measurement of [18F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α7-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [18F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (VT/fP). Results [18F]DBT-10 was produced within 90 min at high specific activities of 428±436 GBq/μmol at end of synthesis. Metabolism of [18F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15–55%. Uptake of [18F]DBT-10 in brain occurred rapidly, reaching peak SUVs of 2.9–3.7 within 30 min. The plasma free fraction was 18.8±3.4%. No evidence for radiolabeled [18F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated VT/fP values were 193–376 mL/cm3 across regions, with regional rank order of thalamus > frontal cortex > striatum > hippocampus > occipital cortex > cerebellum > pons. Dose dependent blockade of [18F]DBT-10 binding by structural analog ASEM was observed throughout the

  17. Biodistribution and radiation dosimetry of 18F-CP-18, a potential apoptosis imaging agent, as determined from PET/CT scans in healthy volunteers.

    PubMed

    Doss, Mohan; Kolb, Hartmuth C; Walsh, Joseph C; Mocharla, Vani; Fan, Hong; Chaudhary, Ashok; Zhu, Zhihong; Alpaugh, R Katherine; Lango, Miriam N; Yu, Jian Q

    2013-12-01

    (18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24-isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from (18)F-CP-18. Successive whole-body PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of (18)F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. (18)F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 ± 4 μSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 μGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 ± 2 μSv/MBq and 142 ± 15 μGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 1.1 mSv for the 1-h interval

  18. Metabolic effects of pulmonary obstruction on myocardial functioning: a pilot study using multiple time-point 18F-FDG-PET imaging.

    PubMed

    Choi, Grace G; Han, Yuchi; Weston, Brian; Ciftci, Esra; Werner, Thomas J; Torigian, Drew; Salavati, Ali; Alavi, Abass

    2015-01-01

    The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the right ventricle (RV) of patients with chronic obstructive pulmonary disease (COPD) and to characterize the variability of 18F-FDG uptake in the RV at different time points following radiotracer administration using PET/computerized tomography (CT). Impaired RV systolic function, RV hypertrophy, and RV dilation are associated with increases in mean pulmonary arterial pressure in patients with COPD. Metabolic changes in the RV using 18F-FDG-PET images 2 and 3 h after tracer injection have not yet been investigated. Twenty-five patients with clinical suspicion of lung cancer underwent 18F-FDG-PET/CT imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUVs) and volumes of RV were recorded from transaxial sections to quantify the metabolic activity. The SUV of RV was higher in patients with COPD stages 1-3 as compared with that in patients with COPD stage 0. RV SUV was inversely correlated with FEV1/FVC pack-years of smoking at 1 h after 18F-FDG injection. In the majority of patients, 18F-FDG activity in RV decreased over time. There was no significant difference in the RV myocardial free wall and chamber volume on the basis of COPD status. The severity of lung obstruction and pack-years of smoking correlate with the level of 18F-FDG uptake in the RV myocardium, suggesting that there may be metabolic changes in the RV associated with lung obstruction that can be detected noninvasively using 18F-FDG-PET/CT. Multiple time-point images of the RV did not yield any additional value in this study.

  19. Comparison of DWI and 18F-FDG PET/CT for assessing preoperative N-staging in gastric cancer: evidence from a meta-analysis.

    PubMed

    Luo, Mingxu; Song, Hongmei; Liu, Gang; Lin, Yikai; Luo, Lintao; Zhou, Xin; Chen, Bo

    2017-10-13

    The diagnostic values of diffusion weighted imaging (DWI) and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for N-staging of gastric cancer (GC) were identified and compared. After a systematic search to identify relevant articles, meta-analysis was used to summarize the sensitivities, specificities, and areas under curves (AUCs) for DWI and PET/CT. To better understand the diagnostic utility of DWI and PET/CT for N-staging, the performance of multi-detector computed tomography (MDCT) was used as a reference. Fifteen studies were analyzed. The pooled sensitivity, specificity, and AUC with 95% confidence intervals of DWI were 0.79 (0.73-0.85), 0.69 (0.61-0.77), and 0.81 (0.77-0.84), respectively. For PET/CT, the corresponding values were 0.52 (0.39-0.64), 0.88 (0.61-0.97), and 0.66 (0.62-0.70), respectively. Comparison of the two techniques revealed DWI had higher sensitivity and AUC, but no difference in specificity. DWI exhibited higher sensitivity but lower specificity than MDCT, and 18 F-FDG PET/CT had lower sensitivity and equivalent specificity. Overall, DWI performed better than 18 F-FDG PET/CT for preoperative N-staging in GC. When the efficacy of MDCT was taken as a reference, DWI represented a complementary imaging technique, while 18 F-FDG PET/CT had limited utility for preoperative N-staging.

  20. Comparison of DWI and 18F-FDG PET/CT for assessing preoperative N-staging in gastric cancer: evidence from a meta-analysis

    PubMed Central

    Luo, Mingxu; Song, Hongmei; Liu, Gang; Lin, Yikai; Luo, Lintao; Zhou, Xin; Chen, Bo

    2017-01-01

    The diagnostic values of diffusion weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for N-staging of gastric cancer (GC) were identified and compared. After a systematic search to identify relevant articles, meta-analysis was used to summarize the sensitivities, specificities, and areas under curves (AUCs) for DWI and PET/CT. To better understand the diagnostic utility of DWI and PET/CT for N-staging, the performance of multi-detector computed tomography (MDCT) was used as a reference. Fifteen studies were analyzed. The pooled sensitivity, specificity, and AUC with 95% confidence intervals of DWI were 0.79 (0.73–0.85), 0.69 (0.61–0.77), and 0.81 (0.77–0.84), respectively. For PET/CT, the corresponding values were 0.52 (0.39–0.64), 0.88 (0.61–0.97), and 0.66 (0.62–0.70), respectively. Comparison of the two techniques revealed DWI had higher sensitivity and AUC, but no difference in specificity. DWI exhibited higher sensitivity but lower specificity than MDCT, and 18F-FDG PET/CT had lower sensitivity and equivalent specificity. Overall, DWI performed better than 18F-FDG PET/CT for preoperative N-staging in GC. When the efficacy of MDCT was taken as a reference, DWI represented a complementary imaging technique, while 18F-FDG PET/CT had limited utility for preoperative N-staging. PMID:29137440

  1. Thyroglobulin levels and thyroglobulin doubling time independently predict a positive 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma.

    PubMed

    Giovanella, Luca; Trimboli, Pierpaolo; Verburg, Frederik A; Treglia, Giorgio; Piccardo, Arnoldo; Foppiani, Luca; Ceriani, Luca

    2013-06-01

    To assess the relationship between serum thyroglobulin (Tg) levels, Tg doubling time (Tg-DT) and the diagnostic performance of (18)F-FDG PET/CT in detecting recurrences of (131)I-negative differentiated thyroid carcinoma (DTC). Included in the present study were 102 patients with DTC. All patients were treated by thyroid ablation (e.g. thyroidectomy and (131)I), and underwent (18)F-FDG PET/CT due to detectable Tg levels and negative conventional imaging. Consecutive serum Tg measurements performed before the (18)F-FDG PET/CT examination were used for Tg-DT calculation. The (18)F-FDG PET/CT results were assessed as true or false after histological and/or clinical follow-up. Serum Tg levels were higher in patients with a positive (18)F-FDG PET/CT scan (median 6.7 ng/mL, range 0.7-73.6 ng/mL) than in patients with a negative scan (median 1.8 ng/mL, range 0.5-4.9 ng/mL; P < 0.001). In 43 (88 %) of 49 patients with a true-positive (18)F-FDG PET/CT scan, the Tg levels were >5.5 ng/mL, and in 31 (74 %) of 42 patients with a true-negative (18)F-FDG PET/CT scan, the Tg levels were ≤5.5 ng/mL. A Tg-DT of <1 year was found in 46 of 49 patients (94 %) with a true-positive (18)F-FDG PET/CT scan, and 40 of 42 patients (95 %) with a true-negative scan had a stable or increased Tg-DT. Moreover, combining Tg levels and Tg-DT as selection criteria correctly distinguished between patients with a positive and a negative scan (P<0.0001). The accuracy of (18)F-FDG PET/CT significantly improves when the serum Tg level is above 5.5 ng/mL during levothyroxine treatment or when the Tg-DT is less than 1 year, independent of the absolute value.

  2. Prognostic value of pre-treatment 18F-FDG PET uptake for nasopharyngeal carcinoma.

    PubMed

    Aktan, Meryem; Kanyilmaz, Gul; Yavuz, Berrin Benli; Koc, Mehmet; Eryılmaz, Mehmet Akif; Adli, Mustafa

    2017-11-25

    To evaluate the prognostic value of maximal standardized uptake values (SUV max ) from serial fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in patients with nasopharyngeal carcinoma (NPC). Fifty-two patients with NPC who underwent 18 F-FDG PET/CT scan before radiotherapy with/without chemotherapy were reviewed retrospectively. Twenty-seven patients (52%) were applied 3-D conformal radiotherapy and 25 patients (48%) applied intensity-modulated radiotherapy (IMRT). Fourteen (27%) patients were given neoadjuvant chemotherapy and forty-four (84.6%) patients were given concomitant and adjuvant chemotherapy. Median follow-up time was 34 months (range 5.6-66.4 months). Forty-four (84.6%) patients were alive at last follow-up and eight (15.4%) had died. The best cut-off value of the SUV max for the primary tumor site (SUV max -PT) was 13 and 9 for the lymph nodes (SUV max -LN). Patients with SUV max -PT ≥ 13.0 and SUV max -LN ≥ 9 had a significantly higher risk for the development of the distant metastases (p = 0.044 and p = 0.038). DFS was affected in patients with SUV max -PT ≥ 13 (log rank χ 2  = 2.54, p = 0.017) and was significantly lower in patients with SUV max -LN ≥ 9 for the lymph nodes (log rank χ 2  = 5.81, p = 0.013). OS was not affected by SUV levels. A multivariate Cox proportional hazard model of DFS included age (≥ 40), SUV max -LN (< 9), T stage (T1-2) and neoadjuvant chemotherapy are significantly better prognosis for the DFS. 18 F-FDG PET/CT uptake before treatment, as determined by SUV max , may be a valuable tool to evaluate prognosis in NPC patients.

  3. [18F]FE@SNAP—A new PET tracer for the melanin concentrating hormone receptor 1 (MCHR1): Microfluidic and vessel-based approaches

    PubMed Central

    Philippe, Cécile; Ungersboeck, Johanna; Schirmer, Eva; Zdravkovic, Milica; Nics, Lukas; Zeilinger, Markus; Shanab, Karem; Lanzenberger, Rupert; Karanikas, Georgios; Spreitzer, Helmut; Viernstein, Helmut; Mitterhauser, Markus; Wadsak, Wolfgang

    2012-01-01

    Changes in the expression of the melanin concentrating hormone receptor 1 (MCHR1) are involved in a variety of pathologies, especially obesity and anxiety disorders. To monitor these pathologies in-vivo positron emission tomography (PET) is a suitable method. After the successful radiosynthesis of [11C]SNAP-7941—the first PET-Tracer for the MCHR1, we aimed to synthesize its [18F]fluoroethylated analogue: [18F]FE@SNAP. Therefore, microfluidic and vessel-based approaches were tested. [18F]fluoroethylation was conducted via various [18F]fluoroalkylated synthons and direct [18F]fluorination. Only the direct [18F]fluorination of a tosylated precursor using a flow-through microreactor was successful, affording [18F]FE@SNAP in 44.3 ± 2.6%. PMID:22921745

  4. Evolving Role of Molecular Imaging with (18)F-Sodium Fluoride PET as a Biomarker for Calcium Metabolism.

    PubMed

    Raynor, William; Houshmand, Sina; Gholami, Saeid; Emamzadehfard, Sahra; Rajapakse, Chamith S; Blomberg, Björn Alexander; Werner, Thomas J; Høilund-Carlsen, Poul F; Baker, Joshua F; Alavi, Abass

    2016-08-01

    (18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.

  5. F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis

    PubMed Central

    Haslerud, Torjan; Brauckhoff, Katrin; Reisæter, Lars; Küfner Lein, Regina; Heinecke, Achim; Varhaug, Jan Erik

    2015-01-01

    Background Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC). Purpose To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy. Material and Methods A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma’s bivariate model. Results Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9–84.1) and 79.4% (95% CI, 71.2–85.4), respectively, with an area under the curve of 0.858. Conclusion F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy. PMID:26163534

  6. Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET.

    PubMed

    Watabe, Tadashi; Hanaoka, Kohei; Naka, Sadahiro; Kanai, Yasukazu; Ikeda, Hayato; Aoki, Masanao; Shimosegawa, Eku; Kirihata, Mitsunori; Hatazawa, Jun

    2017-07-01

    The purpose of this study was to establish a practical method to estimate the absolute boron concentrations in the tissues based on the standardized uptake values (SUVs) after administration of 4-borono-phenylalanine (BPA) using 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) PET. Rat xenograft models of C6 glioma (n = 7, body weight 241 ± 28.0 g) were used for the study. PET was performed 60 min after intravenous injection of 18 F-FBPA (30.5 ± 0.7 MBq). After the PET scanning, BPA-fructose (167.3 ± 18.65 mg/kg) was administered by slow intravenous injection to the same subjects. The rats were killed 60 min after the BPA injection and tissue samples were collected from the major organs and tumors. The absolute boron concentrations (unit: ppm) in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The boron concentrations in the tissues/tumors were also estimated from the 18 F-FBPA PET images using the following formula: estimated absolute boron concentration (ppm) = 0.0478 × [BPA dose (mg/kg)] × SUV. The measured absolute boron concentrations (mBC) by ICP-OES and the estimated boron concentrations (eBC) from the PET images were compared. The percent difference between the mBC and eBC calculated based on the SUV max was -5.2 ± 21.1% for the blood, -9.4 ± 22.3% for the brain, 1.6 ± 21.3% for the liver, -14.3 ± 16.8% for the spleen, -9.5 ± 27.5% for the pancreas, and 3.4 ± 43.2% for the tumor. Relatively large underestimation was observed for the lung (-48.4 ± 16.2%), small intestine (-37.8 ± 19.3%) and large intestine (-33.9 ± 11.0%), due to the partial volume effect arising from the air or feces contained in these organs. In contrast, relatively large overestimation was observed for the kidney (34.3 ± 29.3%), due to the influence of the high uptake in urine. The absolute boron concentrations in tissues/tumors can be estimated from the SUVs on 18 F-FBPA PET using a

  7. Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

    PubMed

    Kaneuchi, Yoichi; Hakozaki, Michiyuki; Yamada, Hitoshi; Hasegawa, Osamu; Tajino, Takahiro; Konno, Shinichi

    2016-01-01

    We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

  8. 18F-FDOPA PET/CT uptake parameters correlate with catecholamines secretion in human pheochromocytomas.

    PubMed

    Moog, Sophie; Moog, Sophie; Houy, Sébastien; Chevalier, Elodie; Ory, Stéphane; Weryha, Georges; Rame, Marion; Klein, Marc; Brunaud, Laurent; Gasman, Stéphane; Cuny, Thomas

    2018-06-27


    Background: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging for the diagnosis of pheochromocytomas (PHEO). However, its utility as a predictive factor of the secretion of catecholamines remains poorly studied. Thirty-nine histologically-confirmed PHEO were included in this retrospective monocentric study. Patients underwent 18F-FDOPA PET/CT before surgery with evaluation of several uptake parameters (SUVmax, SUVmean and the metabolic burden [MB] calculated as follows: MB = SUVmean x tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM) and chromogranin A (CGA). Thirty-five patients were screened for germline mutations in RET, SDHx and VHL genes. Once resected, primary cultures of 5 PHEO were used for real time measurement of catecholamines release by carbon fiber amperometry. The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r=0.64, p<0.0001), MN (r=0.49, p=0.002), combined MN and NM (r=0.75, p<0,0001) and eventually plasma free levels of NM (r=0.55 p=0.006). In mutated-patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL and 3 RET), a similar correlation was observed between the MB and the 24h-urinary combined MN and NM (r=0.86, p=0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p=0.01). While the 18F-FDOPA PET/CT metabolic burden of PHEO strongly correlates with the concentration of metanephrines, amperometric recordings suggest that the 18F-FDOPA uptake could be enhanced by the overactivity of the catecholamines exocytosis.
    . ©2018S. Karger AG, Basel.

  9. In Vivo Imaging of Glial Activation after Unilateral Labyrinthectomy in the Rat: A [18F]GE180-PET Study.

    PubMed

    Zwergal, Andreas; Günther, Lisa; Brendel, Matthias; Beck, Roswitha; Lindner, Simon; Xiong, Guoming; Eilles, Eva; Unterrainer, Marcus; Albert, Nathalie Lisa; Becker-Bense, Sandra; Brandt, Thomas; Ziegler, Sibylle; la Fougère, Christian; Dieterich, Marianne; Bartenstein, Peter

    2017-01-01

    The functional relevance of reactive gliosis for recovery from acute unilateral vestibulopathy is unknown. In the present study, glial activation was visualized in vivo by [ 18 F]GE180-PET in a rat model of unilateral labyrinthectomy (UL) and compared to behavioral vestibular compensation (VC) overtime. 14 Sprague-Dawley rats underwent a UL by transtympanic injection of bupivacaine/arsenilate, 14 rats a SHAM UL (injection of normal saline). Glial activation was depicted with [ 18 F]GE180-PET and ex vivo autoradiography at baseline and 7, 15, 30 days after UL/SHAM UL. Postural asymmetry and nystagmus were registered at 1, 2, 3, 7, 15, 30 days after UL/SHAM UL. Signs of vestibular imbalance were found only after UL, which significantly decreased until days 15 and 30. In parallel, [ 18 F]GE180-PET and ex vivo autoradiography depicted glial activation in the ipsilesional vestibular nerve and nucleus on days 7 and 15 after UL. Correlation analysis revealed a strong negative association of [ 18 F]GE180 uptake in the ipsilesional vestibular nucleus on day 7 with the rate of postural recovery ( R  = -0.90, p  < 0.001), suggesting that glial activation accelerates VC. In conclusion, glial activation takes place in the ipsilesional vestibular nerve and nucleus within the first 30 days after UL in the rat and can be visualized in vivo by [ 18 F]GE180-PET.

  10. In Vivo Imaging of Glial Activation after Unilateral Labyrinthectomy in the Rat: A [18F]GE180-PET Study

    PubMed Central

    Zwergal, Andreas; Günther, Lisa; Brendel, Matthias; Beck, Roswitha; Lindner, Simon; Xiong, Guoming; Eilles, Eva; Unterrainer, Marcus; Albert, Nathalie Lisa; Becker-Bense, Sandra; Brandt, Thomas; Ziegler, Sibylle; la Fougère, Christian; Dieterich, Marianne; Bartenstein, Peter

    2017-01-01

    The functional relevance of reactive gliosis for recovery from acute unilateral vestibulopathy is unknown. In the present study, glial activation was visualized in vivo by [18F]GE180-PET in a rat model of unilateral labyrinthectomy (UL) and compared to behavioral vestibular compensation (VC) overtime. 14 Sprague-Dawley rats underwent a UL by transtympanic injection of bupivacaine/arsenilate, 14 rats a SHAM UL (injection of normal saline). Glial activation was depicted with [18F]GE180-PET and ex vivo autoradiography at baseline and 7, 15, 30 days after UL/SHAM UL. Postural asymmetry and nystagmus were registered at 1, 2, 3, 7, 15, 30 days after UL/SHAM UL. Signs of vestibular imbalance were found only after UL, which significantly decreased until days 15 and 30. In parallel, [18F]GE180-PET and ex vivo autoradiography depicted glial activation in the ipsilesional vestibular nerve and nucleus on days 7 and 15 after UL. Correlation analysis revealed a strong negative association of [18F]GE180 uptake in the ipsilesional vestibular nucleus on day 7 with the rate of postural recovery (R = −0.90, p < 0.001), suggesting that glial activation accelerates VC. In conclusion, glial activation takes place in the ipsilesional vestibular nerve and nucleus within the first 30 days after UL in the rat and can be visualized in vivo by [18F]GE180-PET. PMID:29312111

  11. Estimation of patient radiation dose from whole body 18F- FDG PET/CT examination in cancer imaging: a preliminary study

    NASA Astrophysics Data System (ADS)

    Mahmud, M. H.; Nordin, A. J.; Saad, F. F. Ahmad; Fattah Azman, A. Z.

    2014-11-01

    This study aims to estimate the radiation effective dose resulting from whole body fluorine-18 flourodeoxyglucose Positron Emission Tomography (18F-FDG PET) scanning as compared to conservative Computed Tomography (CT) techniques in evaluating oncology patients. We reviewed 19 oncology patients who underwent 18F-FDG PET/CT at our centre for cancer staging. Internal and external doses were estimated using radioactivity of injected FDG and volume CT Dose Index (CTDIvol), respectively with employment of the published and modified dose coefficients. The median differences of dose among the conservative CT and PET protocols were determined using Kruskal Wallis test with p < 0.05 considered as significant. The median (interquartile range, IQR) effective doses of non-contrasted CT, contrasted CT and PET scanning protocols were 7.50 (9.35) mSv, 9.76 (3.67) mSv and 6.30 (1.20) mSv, respectively, resulting in the total dose of 21.46 (8.58) mSv. Statistically significant difference was observed in the median effective dose between the three protocols (p < 0.01). The effective doses of whole body 18F-FDG PET technique may be effective the lowest amongst the conventional CT imaging techniques.

  12. IMPROVED DERIVATION OF INPUT FUNCTION IN DYNAMIC MOUSE [18F]FDG PET USING BLADDER RADIOACTIVITY KINETICS

    PubMed Central

    Wong, Koon-Pong; Zhang, Xiaoli; Huang, Sung-Cheng

    2013-01-01

    Purpose Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Methods Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. Total accumulated radioactivity in the urinary bladder was fitted to a renal compartmental model with the last blood sample and a 1-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of 4-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects and erythrocytes uptake) and the late-time blood estimates. Using only the blood sample acquired at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. Results The area under the plasma TACs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal

  13. Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT.

    PubMed

    Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia K; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2018-06-05

    Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-( 18 F)fluoro-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy. 25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18 F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients' best clinical response, assessed at a mean of 59 weeks, was used as reference. According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients). Quantitative analysis of 18 F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

  14. Non-invasive estimation of 10 B-4-borono-L-phenylalanine-derived boron concentration in tumors by PET using 4-borono-2-18 F-fluoro-phenylalanine.

    PubMed

    Yoshimoto, Mitsuyoshi; Honda, Natsuki; Kurihara, Hiroaki; Hiroi, Kenta; Nakamura, Satoshi; Ito, Masashi; Shikano, Naoto; Itami, Jun; Fujii, Hirofumi

    2018-05-01

    In boron neutron capture therapy (BNCT), 10 B-4-borono-L-phenylalanine (BPA) is commonly used as a 10 B carrier. PET using 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18 F-FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18 F-FBPA and BPA, and evaluated the utility of 18 F-FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid, an inhibitor of the L-type amino acid transporter, significantly inhibited 18 F-FBPA and 14 C-4-borono-L-phenylalanine ( 14 C-BPA) uptake in FaDu and LN-229 human cancer cells. 18 F-FBPA uptake strongly correlated with 14 C-BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18 F-FBPA was independent of the administration method, and uptake of 18 F-FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18 F-FBPA by PET was useful for estimating 10 B concentration in tumors. © 2018 The Authors.Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. Is 18F-FDG PET/CT useful for distinguishing between primary thyroid lymphoma and chronic thyroiditis?

    PubMed

    Nakadate, Masashi; Yoshida, Katsuya; Ishii, Akihiro; Koizumi, Masayuki; Tochigi, Naobumi; Suzuki, Yoshio; Ryu, Yoshiharu; Nakagawa, Tassei; Umehara, Isao; Shibuya, Hitoshi

    2013-09-01

    This study aims to investigate the usefulness of (18)F-FDG PET/CT for distinguishing between primary thyroid lymphoma (PTL) and chronic thyroiditis. We retrospectively reviewed the data of 196 patients with diffuse (18)F-FDG uptake of the thyroid gland and enrolled patients who were diagnosed as having PTL or chronic thyroiditis based on the medical records, pathological findings, and laboratory data. The enrolled patients comprised 10 PTL patients (M/F = 4:6) and 51 chronic thyroiditis patients (M/F = 8:43). Images had been acquired on a PET/CT scanner at 100 minutes after intravenous injection of (18)F-FDG. The PTL group consisted of 7 patients with diffuse large B-cell lymphoma (DLBCL) and 3 with mucosa-associated lymphoid tissue (MALT) lymphoma. The maximum standardized uptake value (SUV(max)) was significantly higher in the PTL group than that in the chronic thyroiditis group (25.3 ± 8.0 and 7.4 ± 3.2, P < 0.001). On the other hand, the CT density (Hounsfield unit: HU) was significantly lower in the PTL group than that in the chronic thyroiditis group (46.1 ± 7.0 HU and 62.1 ± 6.9 HU, P < 0.001). Within the PTL group, the SUV(max) was significantly higher in the cases of DLBCL than in those of MALT lymphoma (29.0 ± 6.4 and 16.7 ± 2.3, P = 0.017). The SUV(max) was significantly higher and the CT density was significantly lower in PTL as compared with those in chronic thyroiditis. Thus, (18)F-FDG PET/CT may be useful for distinguishing between PTL and chronic thyroiditis.

  16. In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

    PubMed

    Colasanti, Alessandro; Guo, Qi; Muhlert, Nils; Giannetti, Paolo; Onega, Mayca; Newbould, Rexford D; Ciccarelli, Olga; Rison, Stuart; Thomas, Charlotte; Nicholas, Richard; Muraro, Paolo A; Malik, Omar; Owen, David R; Piccini, Paola; Gunn, Roger N; Rabiner, Eugenii A; Matthews, Paul M

    2014-07-01

    PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune

  17. Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

    PubMed

    Ghedini, Pietro; Bossert, I; Zanoni, L; Ceci, F; Graziani, T; Castellucci, P; Ambrosini, V; Massari, F; Nobili, E; Melotti, B; Musto, A; Zoboli, S; Antunovic, L; Kirienko, M; Chiti, A; Mosconi, C; Ardizzoni, A; Golfieri, R; Fanti, S; Nanni, C

    2018-05-01

    were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

  18. Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer.

    PubMed

    Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

    2018-05-01

    The objective of this study was to investigate whether quantitative imaging features derived from combined 18 F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18 F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (≥Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver-operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18 F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. © 2018 by the Society of Nuclear Medicine and Molecular

  19. Movement Correction Method for Human Brain PET Images: Application to Quantitative Analysis of Dynamic [18F]-FDDNP Scans

    PubMed Central

    Wardak, Mirwais; Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Huang, Sung-Cheng

    2010-01-01

    Head movement during a PET scan (especially, dynamic scan) can affect both the qualitative and quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic [18F]-FDDNP PET images of cognitively intact controls and patients with Alzheimer’s disease (AD). Methods Dynamic [18F]-FDDNP PET images, used for in vivo imaging of beta-amyloid plaques and neurofibrillary tangles, were obtained from 12 AD and 9 age-matched controls. For each study, a transmission scan was first acquired for attenuation correction. An accurate retrospective MC method that corrected for transmission-emission misalignment as well as emission-emission misalignment was applied to all studies. No restriction was assumed for zero movement between the transmission scan and first emission scan. Logan analysis with cerebellum as the reference region was used to estimate various regional distribution volume ratio (DVR) values in the brain before and after MC. Discriminant analysis was used to build a predictive model for group membership, using data with and without MC. Results MC improved the image quality and quantitative values in [18F]-FDDNP PET images. In this subject population, medial temporal (MTL) did not show a significant difference between controls and AD before MC. However, after MC, significant differences in DVR values were seen in frontal, parietal, posterior cingulate (PCG), MTL, lateral temporal (LTL), and global between the two groups (P < 0.05). In controls and AD, the variability of regional DVR values (as measured by the coefficient of variation) decreased on average by >18% after MC. Mean DVR separation between controls and ADs was higher in frontal, MTL, LTL and global after MC. Group classification by discriminant analysis based on [18F]-FDDNP DVR values was markedly improved after MC. Conclusion

  20. 18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

    PubMed

    Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

    2018-02-01

    The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

  1. N-(4-[18F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats.

    PubMed

    Frisch, Kim; Stimson, Damion H R; Venkatachalam, Taracad; Pierens, Gregory K; Keiding, Susanne; Reutens, David; Bhalla, Rajiv

    2018-05-04

    Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[ 18 F]fluorobenzyl)cholylglycine ([ 18 F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [ 18 F]FBCGly and a proof-of-concept study by PET/MR in rats. A radiosynthesis of [ 18 F]FBCGly was developed based on reductive alkylation of glycine with 4-[ 18 F]fluorobenzaldehyde followed by coupling to cholic acid. [ 18 F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [ 18 F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [ 18 F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. [ 18 F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected radiochemical yield of 1.0% ± 0.3% (mean ± SD; n = 12). PET/MR studies showed that i.v.-administrated [ 18 F]FBCGly underwent EHC within 40-60 min with a rapid transhepatic transport from blood to bile. In untreated rats, the radioactivity concentration of [ 18 F]FBCGly was approximately 15 times higher in bile than in liver tissue. Cholyltaurine and rifampicin inhibited the biliary secretion of [ 18 F]FBCGly. No fluorine-18 metabolites of [ 18 F]FBCGly were observed. We have developed a radiosynthesis of a novel fluorine-18 labeled bile acid derivative, [ 18 F]FBCGly, and shown by PET/MR that [ 18 F]FBCGly undergoes continuous EHC in rats without metabolizing. This novel tracer may prove useful in PET

  2. Adenocarcinoma with BAC Features Presented as the Nonsolid Nodule Is Prone to Be False-Negative on 18F-FDG PET/CT

    PubMed Central

    Wu, Hu-bing; Wang, Lijuan; Wang, Quan-shi; Han, Yan-jian; Li, Hong-sheng; Zhou, Wen-lan; Tian, Ying

    2015-01-01

    Purpose. The present study investigated which type of adenocarcinoma with BAC features was prone to be false-negative on 18F-FDG PET/CT. Materials and Methods. A retrospective study was performed on 51 consecutive patients with localized adenocarcinoma with BAC features. CT and PET were assessed for lesion size, GGO percentage, and SUVmax. Lesions with FDG uptake the same as or more than mediastinal blood-pool activity were considered as PET-positive. Results. Of the 51 cases, 19.6% presented as pure GGO nodules, 31.4% as mixed nodules, and 49.0% as solid nodules. None of the pure GGO nodules was 18F-FDG avid, compared with 37.5% of mixed nodules and 96.0% of solid nodules (χ 2 = 31.55, P = 0.000). In the mixed nodule group, SUVmax was negatively correlated with GGO percentage (r = −0.588; P = 0.021). The positive detection rate of 18F-FDG PET/CT was 50.0%, 55.6%, and 100% in tumors 1.1–2.0 cm, 2.1–3.0 cm, and >3.0 cm in diameter, respectively (χ 2 = 5.815, P = 0.055). General linear model factor analysis showed that the GGO was an important factor contributing to false-negative PET/CT results (F = 23.992, P = 0.000), but lesion size was not (F = 0.602, P = 0.866). Conclusions. The present study indicated that the adenocarcinoma with BAC features presented as nonsolid nodule is prone to be false negative on 18F-FDG PET/CT. PMID:25879020

  3. Intensity-modulated salvage radiotherapy with simultaneous integrated boost for local recurrence of prostate carcinoma: a pilot study on the place of PET-choline for guiding target volume delineation.

    PubMed

    Wahart, Aurélien; Guy, Jean-Baptiste; Vallard, Alexis; Geissler, Benjamin; Ben Mrad, Majed; Falk, Alexander T; Prevot, Nathalie; de Laroche, Guy; Rancoule, Chloé; Chargari, Cyrus; Magné, Nicolas

    2016-01-01

    The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy. Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume. Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence. Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity. IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

  4. 18F-Fluoride and 18F-Fluorodeoxyglucose Positron Emission Tomography After Transient Ischemic Attack or Minor Ischemic Stroke

    PubMed Central

    Jenkins, William S. A.; Irkle, Agnese; Moss, Alastair; Sng, Greg; Forsythe, Rachael O.; Clark, Tim; Roberts, Gemma; Fletcher, Alison; Lucatelli, Christophe; Rudd, James H. F.; Davenport, Anthony P.; Mills, Nicholas L.; Al-Shahi Salman, Rustam; Dennis, Martin; Whiteley, William N.; van Beek, Edwin J. R.; Dweck, Marc R.; Newby, David E.

    2017-01-01

    Background— Combined positron emission tomography (PET) and computed tomography (CT) can assess both anatomy and biology of carotid atherosclerosis. We sought to assess whether 18F-fluoride or 18F-fluorodeoxyglucose can identify culprit and high-risk carotid plaque. Methods and Results— We performed 18F-fluoride and 18F-fluorodeoxyglucose PET/CT in 26 patients after recent transient ischemic attack or minor ischemic stroke: 18 patients with culprit carotid stenosis awaiting carotid endarterectomy and 8 controls without culprit carotid atheroma. We compared standardized uptake values in the clinically adjudicated culprit to the contralateral asymptomatic artery, and assessed the relationship between radiotracer uptake and plaque phenotype or predicted cardiovascular risk (ASSIGN score [Assessing Cardiovascular Risk Using SIGN Guidelines to Assign Preventive Treatment]). We also performed micro PET/CT and histological analysis of excised plaque. On histological and micro PET/CT analysis, 18F-fluoride selectively highlighted microcalcification. Carotid 18F-fluoride uptake was increased in clinically adjudicated culprit plaques compared with asymptomatic contralateral plaques (log10standardized uptake valuemean 0.29±0.10 versus 0.23±0.11, P=0.001) and compared with control patients (log10standardized uptake valuemean 0.29±0.10 versus 0.12±0.11, P=0.001). 18F-Fluoride uptake correlated with high-risk plaque features (remodeling index [r=0.53, P=0.003], plaque burden [r=0.51, P=0.004]), and predicted cardiovascular risk [r=0.65, P=0.002]). Carotid 18F-fluorodeoxyglucose uptake appeared to be increased in 7 of 16 culprit plaques, but no overall differences in uptake were observed in culprit versus contralateral plaques or control patients. However, 18F-fluorodeoxyglucose did correlate with predicted cardiovascular risk (r=0.53, P=0.019), but not with plaque phenotype. Conclusions— 18F-Fluoride PET/CT highlights culprit and phenotypically high-risk carotid plaque

  5. The Label Matters: μPET Imaging of the Biodistribution of Low Molar Mass 89Zr and 18F-Labeled Poly(2-ethyl-2-oxazoline).

    PubMed

    Glassner, Mathias; Palmieri, Luca; Monnery, Bryn D; Verbrugghen, Thomas; Deleye, Steven; Stroobants, Sigrid; Staelens, Steven; Wyffels, Leonie; Hoogenboom, Richard

    2017-01-09

    Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

  6. Diagnostic performance of an automated analysis software for the diagnosis of Alzheimer’s dementia with 18F FDG PET

    PubMed Central

    Partovi, Sasan; Yuh, Roger; Pirozzi, Sara; Lu, Ziang; Couturier, Spencer; Grosse, Ulrich; Schluchter, Mark D; Nelson, Aaron; Jones, Robert; O’Donnell, James K; Faulhaber, Peter

    2017-01-01

    The objective of this study was to assess the ability of a quantitative software-aided approach to improve the diagnostic accuracy of 18F FDG PET for Alzheimer’s dementia over visual analysis alone. Twenty normal subjects (M:F-12:8; mean age 80.6 years) and twenty mild AD subjects (M:F-12:8; mean age 70.6 years) with 18F FDG PET scans were obtained from the ADNI database. Three blinded readers interpreted these PET images first using a visual qualitative approach and then using a quantitative software-aided approach. Images were classified on two five-point scales based on normal/abnormal (1-definitely normal; 5-definitely abnormal) and presence of AD (1-definitely not AD; 5-definitely AD). Diagnostic sensitivity, specificity, and accuracy for both approaches were compared based on the aforementioned scales. The sensitivity, specificity, and accuracy for the normal vs. abnormal readings of all readers combined were higher when comparing the software-aided vs. visual approach (sensitivity 0.93 vs. 0.83 P = 0.0466; specificity 0.85 vs. 0.60 P = 0.0005; accuracy 0.89 vs. 0.72 P<0.0001). The specificity and accuracy for absence vs. presence of AD of all readers combined were higher when comparing the software-aided vs. visual approach (specificity 0.90 vs. 0.70 P = 0.0008; accuracy 0.81 vs. 0.72 P = 0.0356). Sensitivities of the software-aided and visual approaches did not differ significantly (0.72 vs. 0.73 P = 0.74). The quantitative software-aided approach appears to improve the performance of 18F FDG PET for the diagnosis of mild AD. It may be helpful for experienced 18F FDG PET readers analyzing challenging cases. PMID:28123864

  7. Noninvasive monitoring of cancer therapy induced activated T cells using [18F]FB-IL-2 PET imaging.

    PubMed

    Hartimath, S V; Draghiciu, O; van de Wall, S; Manuelli, V; Dierckx, R A J O; Nijman, H W; Daemen, T; de Vries, E F J

    2017-01-01

    Cancer immunotherapy urgently calls for methods to monitor immune responses at the site of the cancer. Since activated T lymphocytes may serve as a hallmark for anticancer responses, we targeted these cells using the radiotracer N-(4-[ 18 F]fluorobenzoyl)-interleukin-2 ([ 18 F]FB-IL-2) for positron emission tomography (PET) imaging. Thus, we noninvasively monitored the effects of local tumor irradiation and/or immunization on tumor-infiltrating and systemic activated lymphocytes in tumor-bearing mice. A 10- and 27-fold higher [ 18 F]FB-IL-2 uptake was observed in tumors of mice receiving tumor irradiation alone or in combination with immunization, respectively. This increased uptake was extended to several non-target tissues. Administration of the CXCR4 antagonist AMD3100 reduced tracer uptake by 2.8-fold, indicating a CXCR4-dependent infiltration of activated T lymphocytes upon cancer treatment. In conclusion, [ 18 F]FB-IL-2 PET can serve as a clinical biomarker to monitor treatment-induced infiltration of activated T lymphocytes and, on that basis, may guide cancer immunotherapies.

  8. Double match of 18F-fluorodeoxyglucose-PET and iomazenil-SPECT improves outcomes of focus resection surgery.

    PubMed

    Fujimoto, Ayataka; Okanishi, Tohru; Kanai, Sotaro; Sato, Keishiro; Itamura, Shinji; Baba, Shimpei; Nishimura, Mitsuyo; Masui, Takayuki; Enoki, Hideo

    2018-06-01

    When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18 FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. Concordance between interictal 18 FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18 FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

  9. Impact of Endoscopic Ultrasonography on 18F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment.

    PubMed

    Hulshoff, J B; Mul, V E M; de Boer, H E M; Noordzij, W; Korteweg, T; van Dullemen, H M; Nagengast, W B; Oppedijk, V; Pierie, J P E N; Plukker, John Th M

    2017-07-01

    In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography ( 18 F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid 18 F-FDG-PET/CT or 18 F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes.

  10. Metabolic Tumor Volume on 18F-FDG PET/CT Improves Preoperative Identification of High-Risk Endometrial Carcinoma Patients.

    PubMed

    Husby, Jenny A; Reitan, Bernt C; Biermann, Martin; Trovik, Jone; Bjørge, Line; Magnussen, Inger J; Salvesen, Øyvind O; Salvesen, Helga B; Haldorsen, Ingfrid S

    2015-08-01

    Our objective was to prospectively explore the diagnostic value of (18)F-FDG PET/CT for preoperative staging in endometrial carcinomas and to investigate whether (18)F-FDG PET-specific quantitative tumor parameters reflect clinical and histologic characteristics. Preoperative (18)F-FDG PET/CT was prospectively performed on 129 consecutive endometrial carcinoma patients. Two physicians who did not know the clinical findings or staging results independently reviewed the images, assessing primary tumor, cervical stroma involvement and metastatic spread, and determining maximum and mean standardized uptake value (SUVmax and SUVmean, respectively) for tumor, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). All parameters were analyzed in relation to histomorphologic and clinical tumor characteristics. Receiver-operating-characteristic curves for identification of deep myometrial invasion and lymph node metastases were generated, and MTV cutoffs for predicting deep myometrial invasion and lymph node metastases were calculated. The sensitivity, specificity, and accuracy of (18)F-FDG PET/CT for the detection of lymph node metastases were 77%-85%, 91%-96%, and 89%-93%, respectively. SUVmax, SUVmean, MTV, and TLG were significantly related to deep myometrial invasion, presence of lymph node metastases, and high histologic grade (P < 0.015 for all) and independently predicted deep myometrial invasion (P < 0.015) and lymph node metastases (P < 0.025) after adjustment for preoperative histologic risk (based on subtype and grade) in endometrial biopsies. Optimal cutoffs for MTV in predicting deep myometrial invasion (20 mL) and the presence of lymph node metastases (30 mL) yielded odds ratios of 7.8 (P < 0.001) and 16.5 (P = 0.001), respectively. (18)F-FDG PET/CT represents a clinically valuable tool for preoperatively evaluating the presence of lymph node metastases in endometrial carcinoma patients. Applying MTV cutoffs for the prediction of deep myometrial

  11. In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging

    DTIC Science & Technology

    2017-12-01

    AWARD NUMBER: W81XWH-13-1-0138 TITLE: In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical...18Ffluorocholine/ 18F-FDG Cerenkov radiation energy transfer (CRET) coupled with TF- and ErbB2/3- molecularly targeted nearinfrared (NIR) QDs can be used to detect...to examine whether internal illumination via 18F-fluorocholine Cerenkov radiation energy transfer (CRET) coupled with TF- and ErbB2/3- molecularly

  12. Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

    PubMed

    Unterrainer, Marcus; Vettermann, Franziska; Brendel, Matthias; Holzgreve, Adrien; Lifschitz, Michael; Zähringer, Matthias; Suchorska, Bogdana; Wenter, Vera; Illigens, Ben M; Bartenstein, Peter; Albert, Nathalie L

    2017-12-01

    PET with O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18 F-FET PET reading. The background activity of 20 18 F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans. Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more. The commonly applied methods for background activity assessment show different variability which might hamper 18 F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a

  13. Clinical impact of PSMA-based 18F-DCFBC PET/CT imaging in patients with biochemically recurrent prostate cancer after primary local therapy.

    PubMed

    Mena, Esther; Lindenberg, Maria L; Shih, Joanna H; Adler, Stephen; Harmon, Stephanie; Bergvall, Ethan; Citrin, Deborah; Dahut, William; Ton, Anita T; McKinney, Yolanda; Weaver, Juanita; Eclarinal, Philip; Forest, Alicia; Afari, George; Bhattacharyya, Sibaprasad; Mease, Ronnie C; Merino, Maria J; Pinto, Peter; Wood, Bradford J; Jacobs, Paula; Pomper, Martin G; Choyke, Peter L; Turkbey, Baris

    2018-01-01

    The purpose of our study was to assess 18 F-DCFBC PET/CT, a PSMA targeted PET agent, for lesion detection and clinical management of biochemical relapse in prostate cancer patients after primary treatment. This is a prospective IRB-approved study of 68 patients with documented biochemical recurrence after primary local therapy consisting of radical prostatectomy (n = 50), post radiation therapy (n = 9) or both (n = 9), with negative conventional imaging. All 68 patients underwent whole-body 18 F-DCFBC PET/CT, and 62 also underwent mpMRI within one month. Lesion detection with 18 F-DCFBC was correlated with mpMRI findings and pre-scan PSA levels. The impact of 18 F-DCFBC PET/CT on clinical management and treatment decisions was established after 6 months' patient clinical follow-up. Forty-one patients (60.3%) showed at least one positive 18 F-DCFBC lesion, for a total of 79 lesions, 30 in the prostate bed, 39 in lymph nodes, and ten in distant sites. Tumor recurrence was confirmed by either biopsy (13/41 pts), serial CT/MRI (8/41) or clinical follow-up (15/41); there was no confirmation in five patients, who continue to be observed. The 18 F-DCFBC and mpMRI findings were concordant in 39 lesions (49.4%), and discordant in 40 lesions (50.6%); the majority (n = 32/40) of the latter occurring because the recurrence was located outside the mpMRI field of view. 18 F-DCFBC PET positivity rates correlated with PSA values and 15%, 46%, 83%, and 77% were seen in patients with PSA values <0.5, 0.5 to <1.0, 1.0 to <2.0, and ≥2.0 ng/mL, respectively. The optimal cut-off PSA value to predict a positive 18 F-DCFBC scan was 0.78 ng/mL (AUC = 0.764). A change in clinical management occurred in 51.2% (21/41) of patients with a positive 18 F-DCFBC result, generally characterized by starting a new treatment in 19 patients or changing the treatment plan in two patients. 18 F-DCFBC detects recurrences in 60.3% of a population of patients with biochemical recurrence, but

  14. Dual-Gated Motion-Frozen Cardiac PET with Flurpiridaz F 18.

    PubMed

    Slomka, Piotr J; Rubeaux, Mathieu; Le Meunier, Ludovic; Dey, Damini; Lazewatsky, Joel L; Pan, Tinsu; Dweck, Marc R; Newby, David E; Germano, Guido; Berman, Daniel S

    2015-12-01

    A novel PET radiotracer, Flurpiridaz F 18, has undergone phase II clinical trial evaluation as a high-resolution PET cardiac perfusion imaging agent. In a subgroup of patients imaged with this agent, we assessed the feasibility and benefit of simultaneous correction of respiratory and cardiac motion. In 16 patients, PET imaging was performed on a 4-ring scanner in dual cardiac and respiratory gating mode. Four sets of data were reconstructed with high-definition reconstruction (HD•PET): ungated and 8-bin electrocardiography-gated images using 5-min acquisition, optimal respiratory gating (ORG)-as developed for oncologic imaging-using a narrow range of breathing amplitude around end-expiration level with 35% of the counts in a 7-min acquisition, and 4-bin respiration-gated and 8-bin electrocardiography-gated images (32 bins in total) using the 7-min acquisition (dual-gating, using all data). Motion-frozen (MF) registration algorithms were applied to electrocardiography-gated and dual-gated data, creating cardiac-MF and dual-MF images. We computed wall thickness, wall/cavity contrast, and contrast-to-noise ratio for standard, ORG, cardiac-MF, and dual-MF images to assess image quality. The wall/cavity contrast was similar for ungated (9.3 ± 2.9) and ORG (9.5 ± 3.2) images and improved for cardiac-MF (10.8 ± 3.6) and dual-MF images (14.8 ± 8.0) (P < 0.05). The contrast-to-noise ratio was 22.2 ± 9.1 with ungated, 24.7 ± 12.2 with ORG, 35.5 ± 12.8 with cardiac-MF, and 42.1 ± 13.2 with dual-MF images (all P < 0.05). The wall thickness was significantly decreased (P < 0.05) with dual-MF (11.6 ± 1.9 mm) compared with ungated (13.9 ± 2.8 mm), ORG (13.1 ± 2.9 mm), and cardiac-MF images (12.1 ± 2.7 mm). Dual (respiratory/cardiac)-gated perfusion imaging with Flurpiridaz F 18 is feasible and improves image resolution, contrast, and contrast-to-noise ratio when MF registration methods are applied. © 2015 by the Society of Nuclear Medicine and Molecular Imaging

  15. SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, C; Yin, Y

    2014-06-01

    Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters weremore » derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.« less

  16. The Value of 18F-FDG PET/CT Mathematical Prediction Model in Diagnosis of Solitary Pulmonary Nodules

    PubMed Central

    Chen, Yao; Tang, Kun; Lin, Jie

    2018-01-01

    Purpose To establish an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) mathematical prediction model to improve the diagnosis of solitary pulmonary nodules (SPNs). Materials and Methods We retrospectively reviewed 177 consecutive patients who underwent 18F-FDG PET/CT for evaluation of SPNs. The mathematical model was established by logistic regression analysis. The diagnostic capabilities of the model were calculated, and the areas under the receiver operating characteristic curve (AUC) were compared with Mayo and VA model. Results The mathematical model was y = exp⁡(x)/[1 + exp⁡(x)], x = −7.363 + 0.079 × age + 1.900 × lobulation + 1.024 × vascular convergence + 1.530 × pleural retraction + 0.359 × the maximum of standardized uptake value (SUVmax). When the cut-off value was set at 0.56, the sensitivity, specificity, and accuracy of our model were 86.55%, 74.14%, and 81.4%, respectively. The area under the receiver operating characteristic curve (AUC) of our model was 0.903 (95% confidence interval (CI): 0.860 to 0.946). The AUC of our model was greater than that of the Mayo model, the VA model, and PET (P < 0.05) and has no difference with that of PET/CT (P > 0.05). Conclusion The mathematical predictive model has high accuracy in estimating the malignant probability of patients with SPNs. PMID:29789808

  17. Incidence of Brain Metastases on Follow-up 18F-FDG PET/CT Scans of Non-Small Cell Lung Cancer Patients: Should We Include the Brain?

    PubMed

    Nia, Emily S; Garland, Linda L; Eshghi, Naghmehossadat; Nia, Benjamin B; Avery, Ryan J; Kuo, Phillip H

    2017-09-01

    The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18 F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18 F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18 F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18 F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18 F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18 F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18 F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18 F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18 F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution. © 2017 by the Society of

  18. Monitoring of Tumor Growth with [(18)F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches.

    PubMed

    Holzgreve, Adrien; Brendel, Matthias; Gu, Song; Carlsen, Janette; Mille, Erik; Böning, Guido; Mastrella, Giorgia; Unterrainer, Marcus; Gildehaus, Franz J; Rominger, Axel; Bartenstein, Peter; Kälin, Roland E; Glass, Rainer; Albert, Nathalie L

    2016-01-01

    Noninvasive tumor growth monitoring is of particular interest for the evaluation of experimental glioma therapies. This study investigates the potential of positron emission tomography (PET) using O-(2-(18)F-fluoroethyl)-L-tyrosine ([(18)F]-FET) to determine tumor growth in a murine glioblastoma (GBM) model-including estimation of the biological tumor volume (BTV), which has hitherto not been investigated in the pre-clinical context. Fifteen GBM-bearing mice (GL261) and six control mice (shams) were investigated during 5 weeks by PET followed by autoradiographic and histological assessments. [(18)F]-FET PET was quantitated by calculation of maximum and mean standardized uptake values within a universal volume-of-interest (VOI) corrected for healthy background (SUVmax/BG, SUVmean/BG). A partial volume effect correction (PVEC) was applied in comparison to ex vivo autoradiography. BTVs obtained by predefined thresholds for VOI definition (SUV/BG: ≥1.4; ≥1.6; ≥1.8; ≥2.0) were compared to the histologically assessed tumor volume (n = 8). Finally, individual "optimal" thresholds for BTV definition best reflecting the histology were determined. In GBM mice SUVmax/BG and SUVmean/BG clearly increased with time, however at high inter-animal variability. No relevant [(18)F]-FET uptake was observed in shams. PVEC recovered signal loss of SUVmean/BG assessment in relation to autoradiography. BTV as estimated by predefined thresholds strongly differed from the histology volume. Strikingly, the individual "optimal" thresholds for BTV assessment correlated highly with SUVmax/BG (ρ = 0.97, p < 0.001), allowing SUVmax/BG-based calculation of individual thresholds. The method was verified by a subsequent validation study (n = 15, ρ = 0.88, p < 0.01) leading to extensively higher agreement of BTV estimations when compared to histology in contrast to predefined thresholds. [(18)F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model

  19. Textural features and SUV-based variables assessed by dual time point 18F-FDG PET/CT in locally advanced breast cancer.

    PubMed

    Garcia-Vicente, Ana María; Molina, David; Pérez-Beteta, Julián; Amo-Salas, Mariano; Martínez-González, Alicia; Bueno, Gloria; Tello-Galán, María Jesús; Soriano-Castrejón, Ángel

    2017-12-01

    To study the influence of dual time point 18F-FDG PET/CT in textural features and SUV-based variables and their relation among them. Fifty-six patients with locally advanced breast cancer (LABC) were prospectively included. All of them underwent a standard 18F-FDG PET/CT (PET-1) and a delayed acquisition (PET-2). After segmentation, SUV variables (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained. Eighteen three-dimensional (3D) textural measures were computed including: run-length matrices (RLM) features, co-occurrence matrices (CM) features, and energies. Differences between all PET-derived variables obtained in PET-1 and PET-2 were studied. Significant differences were found between the SUV-based parameters and MTV obtained in the dual time point PET/CT, with higher values of SUV-based variables and lower MTV in the PET-2 with respect to the PET-1. In relation with the textural parameters obtained in dual time point acquisition, significant differences were found for the short run emphasis, low gray-level run emphasis, short run high gray-level emphasis, run percentage, long run emphasis, gray-level non-uniformity, homogeneity, and dissimilarity. Textural variables showed relations with MTV and TLG. Significant differences of textural features were found in dual time point 18F-FDG PET/CT. Thus, a dynamic behavior of metabolic characteristics should be expected, with higher heterogeneity in delayed PET acquisition compared with the standard PET. A greater heterogeneity was found in bigger tumors.

  20. Association Between Osteogenesis and Inflammation During the Progression of Calcified Plaque Evaluated by 18F-Fluoride and 18F-FDG.

    PubMed

    Li, Xiang; Heber, Daniel; Cal-Gonzalez, Jacobo; Karanikas, Georgios; Mayerhoefer, Marius E; Rasul, Sazan; Beitzke, Dietrich; Zhang, Xiaoli; Agis, Hermine; Mitterhauser, Markus; Wadsak, Wolfgang; Beyer, Thomas; Loewe, Christian; Hacker, Marcus

    2017-06-01

    18 F-FDG is the most widely validated PET tracer for the evaluation of atherosclerotic inflammation. Recently, 18 F-NaF has also been considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these 2 processes during disease progression. Methods: Thirty-four myeloma patients underwent 18 F-NaF and 18 F-FDG PET/CT examinations. Lesions were divided into 3 groups (noncalcified, mildly calcified, and severely calcified lesions) on the basis of calcium density as measured in Hounsfield units by CT. Tissue-to-background ratios were determined from PET for both tracers. The association between inflammation and osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least 2 examinations with both tracers. Results: There were significant correlations between the maximum tissue-to-background ratios of the 2 tracers (Spearman r = 0.5 [ P < 0.01]; Pearson r = 0.4 [ P < 0.01]) in the 221 lesions at baseline. The highest uptake of both tracers was observed in noncalcified lesions, but without any correlation between the tracers (Pearson r = 0.06; P = 0.76). Compared with noncalcified plaques, mildly calcified plaques showed concordant significantly lower accumulation, with good correlation between the tracers (Pearson r = 0.7; P < 0.01). In addition, enhanced osteogenesis-derived 18 F-NaF uptake and regressive inflammation-derived 18 F-FDG uptake were observed in severely calcified lesions (Pearson r = 0.4; P < 0.01). During follow-up, increased calcium density and increased mean 18 F-NaF uptake were observed, whereas mean 18 F-FDG uptake decreased. Most noncalcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of 18 F-NaF PET imaging and 18 F

  1. Chronic manganism: A long-term follow-up study with a new dopamine terminal biomarker of 18F-FP-(+)-DTBZ (18F-AV-133) brain PET scan.

    PubMed

    Huang, Chu-Yun; Liu, Chi-Hung; Tsao, Eusden; Hsieh, Chia-Ju; Weng, Yi-Hsin; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Lin, Kun-Ju; Huang, Chin-Chang

    2015-01-01

    Recent experimental studies revealed that dopamine neuron dysfunction in chronic manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between manganism and IPD. We conducted a long-term clinical follow-up study of 4 manganism patients, applying a new tracer (18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The (18)F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The (18)F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic manganism and can provide a useful neuroimage biomarker in the differential diagnosis. Copyright © 2015. Published by Elsevier B.V.

  2. Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson's disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging.

    PubMed

    Weng, Chi-Chang; Chen, Zi-An; Chao, Ko-Ting; Ee, Ting-Wei; Lin, Kun-Ju; Chan, Ming-Huan; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Kung, Mei-Ping; Hsu, Ching-Han; Wey, Shiaw-Pyng

    2017-01-01

    18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

  3. IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas.

    PubMed

    Verger, A; Metellus, Ph; Sala, Q; Colin, C; Bialecki, E; Taieb, D; Chinot, O; Figarella-Branger, D; Guedj, E

    2017-08-01

    The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and 18 F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone 18 F-FDOPA PET at an initial stage before surgery and histological diagnosis. 18 F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher 18 F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher 18 F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of 18 F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.

  4. Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0597 TITLE: Parametric PET /MR Fusion Imaging to...Parametric PET /MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies...The study investigates whether fusion PET /MRI imaging with 18F-choline PET /CT and diffusion-weighted MRI can be successfully applied to target prostate

  5. In Vivo Monitoring of Staphylococcus aureus Biofilm Infections and Antimicrobial Therapy by [18F]Fluoro-Deoxyglucose–MicroPET in a Mouse Model

    PubMed Central

    Garrido, Victoria; Collantes, María; Barberán, Montserrat; Peñuelas, Iván; Arbizu, Javier; Amorena, Beatriz

    2014-01-01

    A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [18F]fluoro-deoxyglucose–MicroPET ([18F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [18F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [18F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches. PMID:25155589

  6. Evaluation of focal cortical dysplasia and mixed neuronal and glial tumors in pediatric epilepsy patients using 18F-FDG and 11C-methionine pet.

    PubMed

    Phi, Ji Hoon; Paeng, Jin Chul; Lee, Hyo Sang; Wang, Kyu-Chang; Cho, Byung-Kyu; Lee, Ji-Yeoun; Park, Sung-Hye; Lee, Joongyub; Lee, Dong Soo; Kim, Seung-Ki

    2010-05-01

    Focal cortical dysplasia (FCD) and mixed neuronal and glial tumors share many clinical characteristics; therefore, the presurgical differential diagnosis of these diseases using MRI is difficult in some cases. The aim of this study was to determine whether (11)C-methionine PET, compared with (18)F-FDG PET, was useful for the evaluation of these diseases. The clinical and imaging data of 30 pediatric lesional epilepsy patients pathologically diagnosed with FCD, dysembryoplastic neuroepithelial tumor (DNT), or ganglioglioma were reviewed. Eleven patients had FCD, 8 patients had a DNT, and 11 patients had a ganglioglioma. (18)F-FDG and (11)C-methinine PET scans were obtained from 25 patients and 15 patients, respectively. Visual grading analysis and quantitative assessment of (18)F-FDG and (11)C-methionine PET, represented as a lesion-to-gray matter ratio (LGR), were performed. In the visual grading analysis, both (18)F-FDG PET and (11)C-methionine PET detected a significant difference among the 3 disease groups (P = 0.033 and P = 0.016, respectively), but discrimination of FCD from mixed neuronal and glial tumors was possible only with (11)C-methionine PET. The mean LGR of (18)F-FDG PET was 0.502 +/- 0.119 for FCD, 0.631 +/- 0.107 for DNTs, and 0.620 +/- 0.196 for gangliogliomas; there was no significant difference in LGR among the groups (P = 0.111). However, the mean LGR of (11)C-methionine PET was 1.078 +/- 0.182 for FCD, 1.564 +/- 0.368 for DNT, and 2.114 +/- 0.723 for gangliogliomas; there was a significant difference in LGR among the groups (P = 0.014). Post hoc analysis revealed that the LGR of FCD was significantly different from that of DNTs and gangliogliomas. The mean LGR value of DNTs fell between those of FCD and gangliogliomas. Although (18)F-FDG plays a major role in the preoperative work-up of epilepsy surgery patients, it appears from this study that (18)F-FDG does not contribute to the differential diagnosis and that another tracer such as (11)C

  7. Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

    PubMed

    Werner, Rudolf A; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G; Higuchi, Takahiro

    2015-09-01

    (18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-MIBG) was examined by PET and planar scintigraphy, respectively. Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and

  8. Comparison of 68Ga-labelled PSMA-11 and 11C-choline in the detection of prostate cancer metastases by PET/CT.

    PubMed

    Schwenck, Johannes; Rempp, Hansjoerg; Reischl, Gerald; Kruck, Stephan; Stenzl, Arnulf; Nikolaou, Konstantin; Pfannenberg, Christina; la Fougère, Christian

    2017-01-01

    Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11 C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68 Ga-PSMA-11 with 11 C-choline in patients with primary and recurrent prostate cancer. 123 patients underwent a whole-body PET/CT examination using 68 Ga-PSMA-11 and 11 C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68 Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11 C-choline PET. Also 68 Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by 68 Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11 C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68 Ga-PSMA-11 PET. Thus, PET using 68 Ga-PSMA-11 showed a higher detection rate than 11 C-choline PET for lymph nodes as well as

  9. Development of novel approach to diagnostic imaging of lung cancer with 18F-Nifene PET/CT using A/J mice treated with NNK

    PubMed Central

    Galitovskiy, V; Kuruvilla, SA; Sevriokov, E; Corches, A; Pan, ML; Kalantari-Dehaghi, M; Chernyavsky, AI; Mukherjee, J; Grando, SA

    2017-01-01

    Development of novel methods of early diagnosis of lung cancer is one of the major tasks of contemporary clinical and experimental oncology. In this study, we utilized the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice as an animal model for development of a new imaging technique for early diagnosis of lung cancer. Lung cancer cells in A/J mice overexpress nicotinic acetylcholine receptors. Longitudinal CT scans were carried out over a period of 8 months after NNK treatment, followed by PET/CT scans with 18F-Nifene that binds to α4-made nicotinic receptors with high affinity. PET/CT scans of lungs were also obtained ex vivo. CT revealed the presence of lung nodules in 8-month NNK-treated mice, while control mice had no tumors. Imaging of live animals prior to necropsy allowed correlation of results of tumor load via PET/CT and histopathological findings. Significant amount of 18F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of 18F-Nifene. Quantitative analysis of the extent and amount of 18F-Nifene binding in lung in vivo and ex vivo demonstrated a higher tumor/nontumor ratio due to selective labeling of tumor nodules expressing abundant α4 nicotinic receptor subunits. For comparison, we performed PET/CT studies with 18F-FDG, which is used for the imaging diagnosis of lung cancer. The tumor/nontumor ratios for 18F-FDG were lower than for 18F-Nifene. Thus, we have developed a novel diagnostic imaging approach to early diagnosis of lung cancer using 18F-Nifene PET/CT. This technique allows quantitative assessment of lung tumors in live mice, which is critical for establishing tumor size and location, and also has salient clinical implications. PMID:28553544

  10. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.

    PubMed

    Silveira, Marina B; Ferreira, Soraya M Z M D; Nascimento, Leonardo T C; Costa, Flávia M; Mendes, Bruno M; Ferreira, Andrea V; Malamut, Carlos; Silva, Juliana B; Mamede, Marcelo

    2016-10-01

    [(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [(18)F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. (18)F-glyco-RGD peptides for PET imaging of integrin expression: efficient radiosynthesis by click chemistry and modulation of biodistribution by glycosylation.

    PubMed

    Maschauer, Simone; Haubner, Roland; Kuwert, Torsten; Prante, Olaf

    2014-02-03

    Glycosylation frequently improves the biokinetics and clearance properties of macromolecules in vivo and could therefore be used for the design of radiopharmaceuticals for positron emission tomography (PET). Recently, we have developed a click chemistry method for (18)F-fluoroglycosylation of alkyne-bearing RGD-peptides targeting the integrin receptor. To investigate whether this strategy could yield an (18)F-labeled RGD glycopeptide with favorable biokinetics, we generated a series of new RGD glycopeptides, varying the 6-fluoroglycosyl residue from monosaccharide to disaccharide units, which provided the glucosyl ([(19)F]6Glc-RGD, 4b), galactosyl ([(19)F]Gal-RGD, 4c), maltosyl ([(19)F]Mlt-RGD, 4e), and cellobiosyl ([(19)F]Cel-RGD, 4f) conjugated peptides in high yields and purities of >97%. All of these RGD glycopeptides showed high affinity to αvβ3 (11-55 nM), αvβ5 (6-14 nM), and to αvβ3-positive U87MG cells (90-395 nM). (18)F-labeling of the various carbohydrate precursors (1a-f) using cryptate-assisted reaction conditions (CH3CN, 85 °C, 10 min) gave (18)F-labeled glycosyl azides in radiochemical yields (RCYs) of up to 84% ([(18)F]2b). The deacetylation and subsequent click reaction with the alkyne-bearing cyclic RGD peptide proceeded in one-pot reactions with RCYs as high as 81% in 15-20 min at 60 °C, using a minimal amount of peptide precursor (100 nmol). Optimization of the radiosynthesis strategy gave a decay-uncorrected RCY of 16-24% after 70-75 min (based on [(18)F]fluoride). Due to their high-yield radiosyntheses, the glycopeptides [(18)F]6Glc-RGD and [(18)F]Mlt-RGD were chosen for comparative biodistribution studies and dynamic small-animal PET imaging using U87MG tumor-bearing nude mice. [(18)F]6Glc-RGD and [(18)F]Mlt-RGD showed significantly decreased liver and kidney uptake by PET relative to the 2-[(18)F]fluoroglucosyl analog [(18)F]2Glc-RGD, and showed specific tumor uptake in vivo. Notably, [(18)F]Mlt-RGD revealed uptake and retention in

  12. Comparison of the Cardiac MicroPET Images Obtained Using [(18)F]FPTP and [(13)N]NH3 in Rat Myocardial Infarction Models.

    PubMed

    Kim, Dong-Yeon; Kim, Hyeon Sik; Jang, Hwa Youn; Kim, Ju Han; Bom, Hee-Seung; Min, Jung-Joon

    2014-10-09

    The short half-life of current positron emission tomography (PET) cardiac tracers limits their widespread clinical use. We previously developed a (18)F-labeled phosphonium cation, [(18)F]FPTP, that demonstrated sharply defined myocardial defects in a corresponding infarcted myocardium. The aim of this study was to compare the image properties of PET scans obtained using [(18)F]FPTP with those obtained using [(13)N]NH3 in rat myocardial infarction models. Perfusion abnormality was analyzed in 17 segments of polar map images. The myocardium-to-liver and myocardium-to-lung ratios of [(18)F]FPTP were 10.48 and 2.65 times higher, respectively, than those of [(13)N]NH3 in images acquired 30 min after tracer injection. The myocardial defect size measured by [(18)F]FPTP correlated more closely with the hypoperfused area measured by quantitative 2,3,5-triphenyltetrazolium chloride staining (r = 0.89, P < 0.01) than did [(13)N]NH3 (r = 0.84, P < 0.01). [(18)F]FPTP might be useful as a replacement for the myocardial agent [(13)N]NH3 in cardiac PET/CT applications.

  13. Metabolic impact of partial volume correction of [18F]FDG PET-CT oncological studies on the assessment of tumor response to treatment.

    PubMed

    Stefano, A; Gallivanone, F; Messa, C; Gilardi, M C; Gastiglioni, I

    2014-12-01

    The aim of this work is to evaluate the metabolic impact of Partial Volume Correction (PVC) on the measurement of the Standard Uptake Value (SUV) from [18F]FDG PET-CT oncological studies for treatment monitoring purpose. Twenty-nine breast cancer patients with bone lesions (42 lesions in total) underwent [18F]FDG PET-CT studies after surgical resection of breast cancer primitives, and before (PET-II) chemotherapy and hormone treatment. PVC of bone lesion uptake was performed on the two [18F]FDG PET-CT studies, using a method based on Recovery Coefficients (RC) and on an automatic measurement of lesion metabolic volume. Body-weight average SUV was calculated for each lesion, with and without PVC. The accuracy, reproducibility, clinical feasibility and the metabolic impact on treatment response of the considered PVC method was evaluated. The PVC method was found clinically feasible in bone lesions, with an accuracy of 93% for lesion sphere-equivalent diameter >1 cm. Applying PVC, average SUV values increased, from 7% up to 154% considering both PET-I and PET-II studies, proving the need of the correction. As main finding, PVC modified the therapy response classification in 6 cases according to EORTC 1999 classification and in 5 cases according to PERCIST 1.0 classification. PVC has an important metabolic impact on the assessment of tumor response to treatment by [18F]FDG PET-CT oncological studies.

  14. Comparison of whole body magnetic resonance imaging (WBMRI) to whole body computed tomography (WBCT) or 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) in patients with myeloma: Systematic review of diagnostic performance.

    PubMed

    Gariani, Joanna; Westerland, Olwen; Natas, Sarah; Verma, Hema; Cook, Gary; Goh, Vicky

    2018-04-01

    To undertake a systematic review to determine the diagnostic performance of whole body MRI (WBMRI) including diffusion weighted sequences (DWI) compared to whole body computed tomography (WBCT) or 18 F-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG PET/CT) in patients with myeloma. Two researchers searched the primary literature independently for WBMRI studies of myeloma. Data were extracted focusing on the diagnostic ability of WBMRI versus WBCT and 18 F-FDG PET/CT. Meta-analysis was intended. 6 of 2857 articles were eligible that included 147 patients, published from 2008 to 2016. Studies were heterogeneous including both newly diagnosed & relapsed patients. All were single centre studies. Four of the six studies (66.7%) accrued prospectively and 5/6 (83.3%, 3 prospective) included WBMRI and 18 F-FDG PET/CT. Three of seven (42.9%) included DWI. The lack of an independent reference standard for individual lesions was noted in 5/6 (83.3%) studies. Studies reported that WBMRI detected more lesions than 18 F-FDG PET/CT (sensitivity 68-100% versus 47-100%) but was less specific (specificity 37-83% versus 62-85.7%). No paper assessed impact on management. Studies were heterogeneous, the majority lacking an independent reference standard. Future prospective trials should address these limitations and assess the impact of WBMRI on management. Copyright © 2018. Published by Elsevier B.V.

  15. The use of longitudinal 18F-FET MicroPET imaging to evaluate response to irinotecan in orthotopic human glioblastoma multiforme xenografts.

    PubMed

    Nedergaard, Mette K; Kristoffersen, Karina; Michaelsen, Signe R; Madsen, Jacob; Poulsen, Hans S; Stockhausen, Marie-Thérése; Lassen, Ulrik; Kjaer, Andreas

    2014-01-01

    Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared. Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens. The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts. 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

  16. Dual time point 2-deoxy-2-[18F]fluoro-D-glucose PET/CT: nodal staging in locally advanced breast cancer.

    PubMed

    García Vicente, A M; Soriano Castrejón, A; Cruz Mora, M Á; Ortega Ruiperez, C; Espinosa Aunión, R; León Martín, A; González Ageitos, A; Van Gómez López, O

    2014-01-01

    To assess dual time point 2-deoxy-2-[(18)F]fluoro-D-glucose (18)(F)FDG PET-CT accuracy in nodal staging and in detection of extra-axillary involvement. Dual time point [(18)F] FDG PET/CT scan was performed in 75 patients. Visual and semiquantitative assessment of lymph nodes was performed. Semiquantitative measurement of SUV and ROC-analysis were carried out to calculate SUV(max) cut-off value with the best diagnostic performance. Axillary and extra-axillary lymph node chains were evaluated. Sensitivity and specificity of visual assessment was 87.3% and 75%, respectively. SUV(max) values with the best sensitivity were 0.90 and 0.95 for early and delayed PET, respectively. SUV(max) values with the best specificity were 1.95 and 2.75, respectively. Extra-axillary lymph node involvement was detected in 26.7%. FDG PET/CT detected extra-axillary lymph node involvement in one-fourth of the patients. Semiquantitative lymph node analysis did not show any advantage over the visual evaluation. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  17. 18F-Fluorosulfate for PET Imaging of the Sodium-Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo.

    PubMed

    Khoshnevisan, Alex; Chuamsaamarkkee, Krisanat; Boudjemeline, Mehdi; Jackson, Alex; Smith, Gareth E; Gee, Antony D; Fruhwirth, Gilbert O; Blower, Philip J

    2017-01-01

    Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124 I - and 18 F-BF 4 - We sought new 18 F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18 F-BF 4 - METHODS: The ability of a range of anions, some containing fluorine, to block 99m TcO 4 - uptake in hNIS-expressing cells was measured. SO 3 F - emerged as a promising candidate. 18 F-SO 3 F - was synthesized by reaction of 18 F - with SO 3 -pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO 4 ). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO 4 inhibition. Fluorosulfate was identified as a potent inhibitor of 99m TcO 4 - uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 μM (in comparison with 0.29-4.5 μM for BF 4 - , 0.07 μM for TcO 4 - , and 2.7-4.7 μM for I - ). Radiolabeling to produce 18 F-SO 3 F - was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity > 95%, decay-corrected radiochemical yield = 31.6%, specific activity ≥ 48.5 GBq/μmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 ± 140 and 32 ± 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 ± 21). Fluorosulfate is a high-affinity hNIS substrate. 18 F-SO 3 F - is easily

  18. PSMA-Based [(18)F]DCFPyL PET/CT Is Superior to Conventional Imaging for Lesion Detection in Patients with Metastatic Prostate Cancer.

    PubMed

    Rowe, Steven P; Macura, Katarzyna J; Mena, Esther; Blackford, Amanda L; Nadal, Rosa; Antonarakis, Emmanuel S; Eisenberger, Mario; Carducci, Michael; Fan, Hong; Dannals, Robert F; Chen, Ying; Mease, Ronnie C; Szabo, Zsolt; Pomper, Martin G; Cho, Steve Y

    2016-06-01

    Current standard of care conventional imaging modalities (CIM) such as X-ray computed tomography (CT) and bone scan can be limited for detection of metastatic prostate cancer and therefore improved imaging methods are an unmet clinical need. We evaluated the utility of a novel second-generation low molecular weight radiofluorinated prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer, [(18)F]DCFPyL, in patients with metastatic prostate cancer. Nine patients with suspected prostate cancer recurrence, eight with CIM evidence of metastatic prostate cancer and one with biochemical recurrence, were imaged with [(18)F]DCFPyL PET/CT. Eight of the patients had contemporaneous CIM for comparison. A lesion-by-lesion comparison of the detection of suspected sites of metastatic prostate cancer was carried out between PET and CIM. Statistical analysis for estimated proportions of inter-modality agreement for detection of metastatic disease was calculated accounting for intra-patient correlation using general estimating equation (GEE) intercept-only regression models. One hundred thirty-nine sites of PET positive [(18)F]DCFPyL uptake (138 definite, 1 equivocal) for metastatic disease were detected in the eight patients with available comparison CIM. By contrast, only 45 lesions were identified on CIM (30 definite, 15 equivocal). When lesions were negative or equivocal on CIM, it was estimated that a large portion of these lesions or 0.72 (95 % confidence interval (CI) 0.55-0.84) would be positive on [(18)F]DCFPyL PET. Conversely, of those lesions negative or equivocal on [(18)F]DCFPyL PET, it was estimated that only a very small proportion or 0.03 (95 % CI 0.01-0.07) would be positive on CIM. Delayed 2-h-post-injection time point PET yielded higher tumor radiotracer uptake and higher tumor-to-background ratios than an earlier 1-h-post-injection time point. A novel PSMA-targeted PET radiotracer, [(18)F]DCFPyL, was able to a large

  19. Diagnostic performance of 11C-choline PET/CT and bone scintigraphy in the detection of bone metastases in patients with prostate cancer.

    PubMed

    Kitajima, Kazuhiro; Fukushima, Kazuhito; Yamamoto, Shingo; Kato, Takashi; Odawara, Soichi; Takaki, Haruyuki; Fujiwara, Masayuki; Yamakado, Koichiro; Nakanishi, Yukako; Kanematsu, Akihiro; Nojima, Michio; Hirota, Shozo

    2017-08-01

    The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.

  20. Functional analysis of [methyl-(3)H]choline uptake in glioblastoma cells: Influence of anti-cancer and central nervous system drugs.

    PubMed

    Taguchi, Chiaki; Inazu, Masato; Saiki, Iwao; Yara, Miki; Hara, Naomi; Yamanaka, Tsuyoshi; Uchino, Hiroyuki

    2014-04-01

    Positron emission tomography (PET) and PET/computed tomography (PET-CT) studies with (11)C- or (18)F-labeled choline derivatives are used for PET imaging in glioblastoma patients. However, the nature of the choline transport system in glioblastoma is poorly understood. In this study, we performed a functional characterization of [methyl-(3)H]choline uptake and sought to identify the transporters that mediate choline uptake in the human glioblastoma cell lines A-172 and U-251MG. In addition, we examined the influence of anti-cancer drugs and central nervous system drugs on the transport of [methyl-(3)H]choline. High- and low-affinity choline transport systems were present in A-172 cells, U-251MG cells and astrocytes, and these were Na(+)-independent and pH-dependent. Cell viability in A-172 cells was not affected by choline deficiency. However, cell viability in U-251MG cells was significantly inhibited by choline deficiency. Both A-172 and U-251MG cells have two different choline transporters, choline transporter-like protein 1 (CTL1) and CTL2. In A-172 cells, CTL1 is predominantly expressed, whereas in U-251MG cells, CTL2 is predominantly expressed. Treatment with anti-cancer drugs such as cisplatin, etoposide and vincristine influenced [methyl-(3)H]choline uptake in U-251MG cells, but not A-172 cells. Central nervous system drugs such as imipramine, fluvoxamine, paroxetine, reboxetine, citalopram and donepezil did not affect cell viability or [methyl-(3)H]choline uptake. The data presented here suggest that CTL1 and CTL2 are functionally expressed in A-172 and U-251MG cells and are responsible for [methyl-(3)H]choline uptake that relies on a directed H(+) gradient as a driving force. Furthermore, while anti-cancer drugs altered [methyl-(3)H]choline uptake, central nervous system drugs did not affect [methyl-(3)H]choline uptake. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Preoperative Staging With 11C-Choline PET/CT Is Adequately Accurate in Patients With Very High-Risk Prostate Cancer.

    PubMed

    Schiavina, Riccardo; Bianchi, Lorenzo; Mineo Bianchi, Federico; Borghesi, Marco; Pultrone, Cristian Vincenzo; Dababneh, Hussam; Castellucci, Paolo; Ceci, Francesco; Nanni, Cristina; Gaudiano, Caterina; Fiorentino, Michelangelo; Porreca, Angelo; Chessa, Francesco; Minervini, Andrea; Fanti, Stefano; Brunocilla, Eugenio

    2018-05-30

    To evaluate the accuracy of 11 C-choline positron emission tomography (PET)/computed tomography (CT) for nodal staging of prostate cancer (PCa) in different populations of high-risk patients. We evaluated 262 individuals with intermediate- or high-risk PCa submitted to radical prostatectomy and extended pelvic lymph node dissection. Within men with high-risk disease, we identified a subgroup of individuals harboring very high-risk (VHR, n = 28) disease: clinical stage ≥ T2c and more than 5 cores with Gleason score 8-10; primary biopsy Gleason score of 5; 3 high-risk features; or prostate-specific antigen ≥ 30 ng/mL. The diagnostic accuracy of PET/CT and contrast-enhanced CT (CECT) was assessed after stratifying patients according to risk group classification on a patient- and anatomic region-based analysis. On patient-based analysis, considering high-risk patients (n = 155), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 50% and 76% versus 21% and 92%, respectively. Considering VHR men as separate subgroups (n = 28), 11 C-choline PET/CT versus CECT had sensitivity and specificity of 71% and 93% versus 25% and 79%, respectively. Accordingly, in the VHR category, the area under the curve of 11 C-choline PET/CT versus CECT was 0.86 (95% confidence interval, 0.71-1.0) versus 0.69 (95% confidence interval, 0.52-0.86), respectively. On anatomic region-based analysis, considering the VHR group, 11 C-choline PET/CT versus CECT had sensitivity and specificity of 70.6% and 95.5% versus 35.3% and 98.5%, respectively. Patients with VHR characteristics could represent the ideal candidate to undergo disease staging with PET/CT before surgery with the highest cost efficacy. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Importance of 18F-FDG PET/CT to select patients with nonresectable colorectal liver metastases for liver transplantation.

    PubMed

    Grut, Harald; Revheim, Mona-Elisabeth; Line, Pål-Dag; Dueland, Svein

    2018-04-20

    The aim of this study was to evaluate fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT for the selection of patients with nonresectable colorectal liver metastases (NCLM) for liver transplantation (LT). In the secondary cancer study, we reported an improved 5-year overall survival in patients treated with LT for NCLM (56%) compared with chemotherapy (9%). However, many patients were rejected for LT owing to the detection of extrahepatic disease at preoperative imaging. F-FDG PET/CT and contrast-enhanced computed tomography (ceCT) examinations before tentative LT for NCLM were assessed, and findings contraindicating LT were registered. Maximum, mean and peak standardized uptake values; tumor-to-background ratio; metabolic tumor volume; and total lesion glycolysis were measured and calculated for all liver metastases. Overall survival was calculated by the Kaplan-Meier method. Thirty-two patients excluded by F-FDG PET/CT and/or ceCT before tentative LT for NCLM were identified. F-FDG PET/CT from 20 of the 32 excluded patients revealed extrahepatic disease. Eight of the other 12 patients had a negative F-FDG PET/CT finding but were excluded by ceCT. Ten patients were excluded by F-FDG PET/CT only. Four patients were excluded owing to detected malignancy from frozen sections at the start of the intended transplant operation. Tumor-to-background ratio of the liver metastases was significantly higher in patients where F-FDG PET/CT detected extrahepatic disease (P=0.03). The median (range) survival after exclusion was 16 (0-52) months. The ability of F-FDG PET/CT to detect extrahepatic disease before LT for NCLM is vital to establish LT as a treatment option.

  3. Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies.

    PubMed

    Kim, Dong Hyun; Choe, Yearn Seong; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae

    2011-05-01

    Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study

    PubMed Central

    Andrzejewski, Piotr; Baltzer, Pascal; Polanec, Stephan H.; Sturdza, Alina; Georg, Dietmar; Helbich, Thomas H.; Karanikas, Georgios; Grimm, Christoph; Polterauer, Stephan; Poetter, Richard; Wadsak, Wolfgang; Mitterhauser, Markus; Georg, Petra

    2016-01-01

    Objectives To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Materials and Methods Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. Results All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05–0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. Conclusion MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT. PMID:27167829

  5. Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study.

    PubMed

    Pinker, Katja; Andrzejewski, Piotr; Baltzer, Pascal; Polanec, Stephan H; Sturdza, Alina; Georg, Dietmar; Helbich, Thomas H; Karanikas, Georgios; Grimm, Christoph; Polterauer, Stephan; Poetter, Richard; Wadsak, Wolfgang; Mitterhauser, Markus; Georg, Petra

    2016-01-01

    To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05-0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.

  6. Analysis of 18F-fluorodeoxy-glucose PET imaging data captured before and after Pc 4-mediated photodynamic therapy of U87 tumors in the athymic nude rat

    NASA Astrophysics Data System (ADS)

    Cross, Nathan; Varghai, Davood; Spring-Robinson, Chandra; Sharma, Rahul; Muzic, Raymond F., Jr.; Oleinick, Nancy L.; Dean, D.

    2007-02-01

    Introduction: Several workers have proposed the use of PET (Positron Emission Tomography) imaging for the outcome assessment of photodynamic therapy (PDT), especially for deep-seated tumors. We report on our study of 18Ffluorodeoxy- glucose (18F-FDG) PET imaging following brain tumor Pc4-PDT. Our working hypothesis was that the tumor's metabolic activity would decline dramatically following Pc 4-PDT owing to tumor necrosis. Methods: Seven days after intraparenchymal implantation of U87 cells, the brains of 12 athymic nude rats were imaged by micro-CT and/or micro-MR. These animals were also 18F-FDG micro-PETPET) scanned before and after Pc 4-PDT. 18F-FDG was used to trace metabolic activity that was monitored via μPET. Occurrence of PDT was confirmed on histology. The analysis of 18F-FDG dose and animal weight normalized μPET activity was studied over the 90 minute µPET scan. Results: Currently, μPET data have been studied for: (1) three of the animals that did not indicate tumor necrosis on histology and were assigned to a "Non-PDT" group, and (2) six animals that exhibited tumor necrosis on histology and were assigned to a "PDT" group. The μPET-detected 18F-FDG uptake activity in the tumor region before and after photoirradiation increased in the Non-PDT group an average of 2.28 times, and in the PDT group it increased an average of 1.15 times. Discussion: We are investigating the cause of the increase in 18F-FDG μPET activity that we observed in the PDT group. The methodology used in this study should be useful in determining whether this or other PET, SPECT, or MR functional imaging protocols will detect both the specificity and sensitivity of brain tumor necrosis following Pc 4-PDT.

  7. Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson’s disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging

    PubMed Central

    Chao, Ko-Ting; Ee, Ting-Wei; Lin, Kun-Ju; Chan, Ming-Huan; Hsiao, Ing-Tsung; Yen, Tzu-Chen; Kung, Mei-Ping; Hsu, Ching-Han

    2017-01-01

    18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson’s disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP–PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD. PMID:28257461

  8. Parapharyngeal neuroglial heterotopia appearing as high uptake on 18F-FDG PET: case report and literature review of radiographical findings.

    PubMed

    Kameyama, Masayuki; Kawaguchi, Tomohiro; Niizuma, Hidetaka; Ogawa, Takenori; Watanabe, Kenichi; Hayashi, Toshiaki; Sato, Kanako; Kanamori, Masayuki; Watanabe, Mika; Katori, Yukio; Kure, Shigeo; Tominaga, Teiji

    2018-04-01

    Parapharyngeal neuroglial heterotopia is a rare entity, and the specific radiographical findings are unclear. We present a case of parapharyngeal neuroglial heterotopia examined with proton magnetic resonance spectroscopy ( 1 H-MRS) and 18 F-fluorodesoxyglucose positron emission tomography ( 18 F-FDG PET). Our neonate patient presented with neck mass and polyhydramnios during gestation. Computed tomography and magnetic resonance imaging demonstrated the morphological characteristics, but failed to establish the diagnosis. 1 H-MRS showed a non-malignant pattern, but 18 F-FDG PET demonstrated high glucose metabolism. Complete resection was achieved and the histopathological diagnosis was neuroglial heterotopia. Assessment of biological activity may be useful for both preoperative diagnosis and postoperative evaluation of residual lesions.

  9. [18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia.

    PubMed

    Tan, Chengbo; Zhao, Songji; Higashikawa, Kei; Wang, Zifeng; Kawabori, Masahito; Abumiya, Takeo; Nakayama, Naoki; Kazumata, Ken; Ukon, Naoyuki; Yasui, Hironobu; Tamaki, Nagara; Kuge, Yuji; Shichinohe, Hideo; Houkin, Kiyohiro

    2018-05-02

    The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [ 18 F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [ 18 F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [ 18 F]DPA-714 PET was performed 3 and 10 days after MCAO. Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [ 18 F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group. The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [ 18 F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

  10. A rare adult renal neuroblastoma better imaged by 18F-FDG than by 68Ga-dotanoc in the PET/CT scan.

    PubMed

    Jain, Tarun Kumar; Singh, Sharwan Kumar; Sood, Ashwani; Ashwathanarayama, Abhiram Gj; Basher, Rajender Kumar; Shukla, Jaya; Mittal, Bhagwant Rai

    2017-01-01

    Primary renal neuroblastoma is an uncommon tumor in children and extremely rare in adults. We present a case of a middle aged female having a large retroperitoneal mass involving the right kidney with features of neuroblastoma on pre-operative histopathology. Whole-body fluorine-18-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG PET/CT) and 68 Ga-dotanoc PET/CT scans performed for staging and therapeutic potential revealed a tracer avid mass replacing the right kidney and also pelvic lymph nodes. The 18 F-FDG PET/CT scan showed better both the primary lesion and the metastases in the pelvic lymph nodes than the 68 Ga-dotanoc scan supporting diagnosis and treatment planning.

  11. Pharmacokinetics, metabolism, biodistribution, radiation dosimetry, and toxicology of (18)F-fluoroacetate ((18)F-FACE) in non-human primates.

    PubMed

    Nishii, Ryuichi; Tong, William; Wendt, Richard; Soghomonyan, Suren; Mukhopadhyay, Uday; Balatoni, Julius; Mawlawi, Osama; Bidaut, Luc; Tinkey, Peggy; Borne, Agatha; Alauddin, Mian; Gonzalez-Lepera, Carlos; Yang, Bijun; Gelovani, Juri G

    2012-04-01

    To facilitate the clinical translation of (18)F-fluoroacetate ((18)F-FACE), the pharmacokinetics, biodistribution, radiolabeled metabolites, radiation dosimetry, and pharmacological safety of diagnostic doses of (18)F-FACE were determined in non-human primates. (18)F-FACE was synthesized using a custom-built automated synthesis module. Six rhesus monkeys (three of each sex) were injected intravenously with (18)F-FACE (165.4 ± 28.5 MBq), followed by dynamic positron emission tomography (PET) imaging of the thoracoabdominal area during 0-30 min post-injection and static whole-body PET imaging at 40, 100, and 170 min. Serial blood samples and a urine sample were obtained from each animal to determine the time course of (18)F-FACE and its radiolabeled metabolites. Electrocardiograms and hematology analyses were obtained to evaluate the acute and delayed toxicity of diagnostic dosages of (18)F-FACE. The time-integrated activity coefficients for individual source organs and the whole body after administration of (18)F-FACE were obtained using quantitative analyses of dynamic and static PET images and were extrapolated to humans. The blood clearance of (18)F-FACE exhibited bi-exponential kinetics with half-times of 4 and 250 min for the fast and slow phases, respectively. A rapid accumulation of (18)F-FACE-derived radioactivity was observed in the liver and kidneys, followed by clearance of the radioactivity into the intestine and the urinary bladder. Radio-HPLC analyses of blood and urine samples demonstrated that (18)F-fluoride was the only detectable radiolabeled metabolite at the level of less than 9% of total radioactivity in blood at 180 min after the (18)F-FACE injection. The uptake of free (18)F-fluoride in the bones was insignificant during the course of the imaging studies. No significant changes in ECG, CBC, liver enzymes, or renal function were observed. The estimated effective dose for an adult human is 3.90-7.81 mSv from the administration of 185

  12. Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

    PubMed

    Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

    2010-05-01

    The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

  13. The combination of 13N-ammonia and 18F-FDG whole-body PET/CT on the same day for diagnosis of advanced prostate cancer

    PubMed Central

    Yi, Chang; Yu, Donglan; Shi, Xinchong; Luo, Ganhua; He, Qiao; Zhang, Xuezhen

    2016-01-01

    Purpose The aim of the study was to evaluate the efficacy of 13N-ammonia and 18F-fluorodeoxyglucose (18F-FDG) PET performed on the same day in the detection of advanced prostate cancer (PC) and its metastases. Patients and methods Twenty-six patients with high-risk PC [Gleason score 8–10 or prostate-specific antigen (PSA)>20 ng/ml or clinical tumor extension≥T2c] were recruited into the study. 13N-Ammonia and 18F-FDG PET/CT were performed on the same day (18F-FDG followed ammonia, with an interval of a minimum of 2 h). Lesions were interpreted as positive, negative, or equivocal. Patient-based and field-based performance characteristics for both imaging techniques were reported. Results There was significant correlation between 13N-ammonia and 18F-FDG PET/CT in the detection of primary PC (κ=0.425, P=0.001) and no significant difference in sensitivity (60.2 vs. 54.5%) and specificity (100 vs. 83.3%). The maximum standard uptake values and corresponding target-to-background ratio values of the concordantly positive lesions in prostate glands in the two studies did not differ significantly (P=0.124 and 0.075, respectively). The sensitivity and specificity of PET imaging using 13N-ammonia for lymph node metastases were 77.5 and 96.3%, respectively, whereas the values were 75 and 44.4% using 18F-FDG. The two modalities were highly correlated with respect to the detection of lymph nodes and bone metastases. Conclusion The concordance between the two imaging modalities suggests a clinical impact of 13N-ammonia PET/CT in advanced PC patients as well as of 18F-FDG. 13N-Ammonia is a useful PET tracer and a complement to 18F-FDG for detecting primary focus and distant metastases in PC. The combination of these two tracers on the same day can accurately detect advanced PC. PMID:26588068

  14. IgG4-Related Disease Simulating Carcinoma Colon With Diffuse Peritoneal Carcinomatosis on 18F-FDG PET/CT.

    PubMed

    Vadi, Shelvin Kumar; Parihar, Ashwin Singh; Kumar, Rajender; Singh, Harmandeep; Mittal, Bhagwant Rai; Bal, Amanjit; Sinha, Saroj Kumar

    2018-05-14

    IgG4-related disease (IgG4-RD) continues to be a diagnostic challenge and a great mimicker of malignancies. We report here a case of young man who presented with subacute intestinal obstruction with initial imaging and clinical features suggestive of carcinoma colon. 18F-FDG PET/CT showed diffuse peritoneal carcinomatosis pattern typically seen with abdominal malignancies. However, the histopathology and the raised IgG4 levels diagnosed it to be IgG4-RD. Although 18F-FDG PET/CT has typical patterns corresponding to the multisystemic involvement of IgG4-RD, the index case did not show any such findings.

  15. Radiosynthesis and initial characterization of a PDE10A specific PET tracer [18F]AMG 580 in non-human primates.

    PubMed

    Hwang, Dah-Ren; Hu, Essa; Allen, Jennifer R; Davis, Carl; Treanor, James; Miller, Silke; Chen, Hang; Shi, Bingzhi; Narayanan, Tanjorie K; Barret, Olivier; Alagille, David; Yu, Zhigang; Slifstein, Mark

    2015-08-01

    Phosphodiesterase 10A (PDE10A) is an intracellular enzyme responsible for the breakdown of cyclic nucleotides which are important second messengers for neurotransmission. Inhibition of PDE10A has been identified as a potential target for treatment of various neuropsychiatric disorders. To assist drug development, we have identified a selective PDE10A positron emission tomography (PET) tracer, AMG 580. We describe here the radiosynthesis of [(18)F]AMG 580 and in vitro and in vivo characterization results. The potency and selectivity were determined by in vitro assay using [(3)H]AMG 580 and baboon brain tissues. [(18)F]AMG 580 was prepared by a 1-step [(18)F]fluorination procedure. Dynamic brain PET scans were performed in non-human primates. Regions-of-interest were defined on individuals' MRIs and transferred to the co-registered PET images. Data were analyzed using two tissue compartment analysis (2TC), Logan graphical (Logan) analysis with metabolite-corrected input function and the simplified reference tissue model (SRTM) method. A PDE10A inhibitor and unlabeled AMG 580 were used to demonstrate the PDE10A specificity. KD was estimated by Scatchard analysis of high and low affinity PET scans. AMG 580 has an in vitro KD of 71.9 pM. Autoradiography showed specific uptake in striatum. Mean activity of 121 ± 18 MBq was used in PET studies. In Rhesus, the baseline BPND for putamen and caudate was 3.38 and 2.34, respectively, via 2TC, and 3.16, 2.34 via Logan, and 2.92, and 2.01 via SRTM. A dose dependent decrease of BPND was observed by the pre-treatment with a PDE10A inhibitor. In baboons, 0.24 mg/kg dose of AMG 580 resulted in about 70% decrease of BPND. The in vivo KD of [(18)F]AMG 580 was estimated to be around 0.44 nM in baboons. [(18)F]AMG 580 is a selective and potent PDE10A PET tracer with excellent specific striatal binding in non-human primates. It warrants further evaluation in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Static and dynamic 18F-FET PET for the characterization of gliomas defined by IDH and 1p/19q status.

    PubMed

    Verger, Antoine; Stoffels, Gabriele; Bauer, Elena K; Lohmann, Philipp; Blau, Tobias; Fink, Gereon R; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

    2018-03-01

    The molecular features isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion have gained major importance for both glioma typing and prognosis and have, therefore, been integrated in the World Health Organization (WHO) classification in 2016. The aim of this study was to characterize static and dynamic O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET parameters in gliomas with or without IDH mutation or 1p/19q co-deletion. Ninety patients with newly diagnosed and untreated gliomas with a static and dynamic 18 F-FET PET scan prior to evaluation of tumor tissue according to the 2016 WHO classification were identified retrospectively. Mean and maximum tumor-to-brain ratios (TBR mean/max ), as well as dynamic parameters (time-to-peak and slope) of 18 F-FET uptake were calculated. Sixteen (18%) oligodendrogliomas (IDH mutated, 1p/19q co-deleted), 27 (30%) astrocytomas (IDH mutated only), and 47 (52%) glioblastomas (IDH wild type only) were identified. TBR mean , TBR max , TTP and slope discriminated between IDH mutated astrocytomas and IDH wild type glioblastomas (P < 0.01). TBR mean showed the best diagnostic performance (cut-off 1.95; sensitivity, 89%; specificity, 67%; accuracy, 81%). None of the parameters discriminated between oligodendrogliomas (IDH mutated, 1p/19q co-deleted) and glioblastomas or astrocytomas. Furthermore, TBR mean , TBR max , TTP, and slope discriminated between gliomas with and without IDH mutation (p < 0.01). The best diagnostic performance was obtained for the combination of TTP with TBR max or slope (accuracy, 73%). Data suggest that static and dynamic 18 F-FET PET parameters may allow determining non-invasively the IDH mutation status. However, IDH mutated and 1p/19q co-deleted oligodendrogliomas cannot be differentiated from glioblastomas and astrocytomas by 18 F-FET PET.

  17. Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma

    PubMed Central

    Foster, Brent; Boutin, Robert D.; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D.; Li, Chin-Shang; Canter, Robert J.; Chaudhari, Abhijit J.

    2018-01-01

    The aim of this study was to determine the association of measures of skeletal muscle determined from 18F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma. PMID:29756042

  18. Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma.

    PubMed

    Foster, Brent; Boutin, Robert D; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D; Li, Chin-Shang; Canter, Robert J; Chaudhari, Abhijit J

    2018-01-01

    The aim of this study was to determine the association of measures of skeletal muscle determined from 18 F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18 F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

  19. 18F-FDG or 3'-deoxy-3'-18F-fluorothymidine to detect transformation of follicular lymphoma.

    PubMed

    Wondergem, Marielle J; Rizvi, Saiyada N F; Jauw, Yvonne; Hoekstra, Otto S; Hoetjes, Nikie; van de Ven, Peter M; Boellaard, Ronald; Chamuleau, Martine E D; Cillessen, Saskia A G M; Regelink, Josien C; Zweegman, Sonja; Zijlstra, Josée M

    2015-02-01

    Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that (18)F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) might be superior to (18)F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a head-to-head comparison of (18)F-FDG and (18)F-FLT in patients with FL and TF. (18)F-FDG and (18)F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUVmax), defined as the lymph node with the highest uptake per patient, and SUVrange, defined as the difference between the SUVmax of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm(3) (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of (18)F-FDG or (18)F-FLT. To determine the discriminative ability of SUVmax and SUVrange of both tracers for TF, receiver-operating-characteristic curve analysis was performed. The highest SUVmax was significantly higher for TF than FL for both (18)F-FDG and (18)F-FLT (P < 0.001). SUVrange was significantly higher for TF than FL for (18)F-FDG (P = 0.029) but not for (18)F-FLT (P = 0.075). The ability of (18)F-FDG to discriminate between FL and TF was superior to that of (18)F-FLT for both the highest SUVmax (P = 0.039) and the SUVrange (P = 0.012). The cutoff value for the highest SUVmax of (18)F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For (18)F-FLT, these values were

  20. Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using 18F-FDG PET Imaging

    PubMed Central

    Coleman, Robert A.; Liang, Christopher; Patel, Rima; Ali, Sarah

    2017-01-01

    Objective: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of β-amyloid plaques. We report 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice. Methods: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq 18F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. 18F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed. Results: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as −20%, while changes in cerebellum were −3%. Uptake of 18F-FDG in IBAT decreased by −60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice. Conclusion: Our results suggest that 18F-FDG uptake in the Tg2576 mice brain show 18F-FDG deficits only when blood glucose is taken into consideration. PMID:28654383

  1. Synthesis and Evaluation of 15-(4-(2-[18F]Fluoroethoxy)phenyl)pentadecanoic Acid: a Potential PET Tracer for Studying Myocardial Fatty Acid Metabolism

    PubMed Central

    Tu, Zhude; Li, Shihong; Sharp, Terry L.; Herrero, Pilar; Dence, Carmen S.; Gropler, Robert J.; Mach, Robert H.

    2010-01-01

    15-(4-(2-[18F]fluoroethoxy)phenyl)pentadecanoic acid ([18F]7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [18F]7 was accomplished using a two step reaction, starting with the corresponding tosylate ester, methyl 15-(4-(2-(tosyloxy)ethoxy)phenyl)pentadecanoate (5) and gave the radiolabeled fatty acid, [18F]7 in a radiolabeling yield of 55 – 60% and a specific activity of > 2,000 Ci/mmol (decay corrected to EOB). The biological evaluation of [18F]7 in rats displayed high uptake in heart (1.94%.ID/g at 5 min), which was higher than the uptake (%ID/g) in blood, lung, muscle, pancreas and brain. MicroPET studies of [18F]7 in Sprague-Dawley rats demonstrated excellent images of the myocardium when compared with [11C]palmitate images in the same animal. Moreover, the tracer kinetics of [18F]7 paralleled those seen with [11C]palmitate, with an early peak followed by biphasic washout. When compared to [11C]palmitate, [18F]7 exhibited a slower early clearance (0.17 ± 0.01 vs. 0.30 ± 0.02, P < 0.0001) and a significantly higher late clearance (0.0030 ± 0.0005 vs. 0.0006 ± 0.00013, P < 0.01). These initial studies suggest that [18F]7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism. PMID:21070001

  2. Role of 18F-FDG PET/CT in diagnosing peritoneal carcinomatosis in the restaging of patient with ovarian cancer as compared to contrast enhanced CT and tumor marker Ca-125.

    PubMed

    Rubini, G; Altini, C; Notaristefano, A; Merenda, N; Rubini, D; Ianora, A A Stabile; Asabella, A Niccoli

    2014-01-01

    To investigate the role of whole-body fluorine-18-2-deoxy-2-fluoro-d-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the identification of peritoneal carcinomatosis in patients with ovarian cancer (OC). Seventy-nine patients with histologically proven stages III-IV OC who underwent (18)F-FDG PET/CT were studied retrospectively. We considered group A as 51 patients who also underwent computed-tomography with contrast-enhancement (CECT), and group B as 35 patients who had also been tested for biomarker Ca-125. Sensitivity, specificity, accuracy, positive predictive values (PPV) and negative predictive values (NPV) of (18)F-FDG PET/CT as compared to CECT and to Ca-125 were evaluated. (18)F-FDG PET/CT' sensitivity, specificity, accuracy, PPV and NPV for all 79 patients were: 85%, 92.31%, 88.61%, 91.89% and 85.71%, respectively. (18)F-FDG PET/CT sensitivity in group A was 78.6%, while it was 53.6% for CECT. (18)F-FDG PET/CT specificity, calculated in the same group, was 91.3%, while that of CECT was 60.9% (statistically significant difference, McNemar 4, P=0.039). Accuracy was 84.3% and 56.9%, respectively. (18)F-FDG PET/CT' sensitivity in group B was 86.4%, while that of Ca-125 was 81.8% (no statistical difference, McNemar 0, P=1). (18)F-FDG PET/CT specificity in group B was 84.6% while that of Ca-125 was 38.5% (clear but not statistically significant difference, McNemar 3.12, P=0.070). Accuracy calculated in the same group was 85.7% for (18)F-FDG PET/CT and 65.7% for Ca-125. (18)F-FDG PET/CT is a useful diagnostic tool when peritoneal biopsy cannot be performed and it can better select those who are candidates for adjuvant chemotherapy. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  3. In vivo evaluation of [18F]FEAnGA-Me: a PET tracer for imaging β-glucuronidase (β-GUS) activity in a tumor/inflammation rodent model.

    PubMed

    Antunes, Inês F; Haisma, Hidde J; Elsinga, Philip H; Sijbesma, Jurgen W A; Waarde, Aren van; Willemsen, Antoon T M; Dierckx, Rudi A; de Vries, Erik F J

    2012-08-01

    The PET tracer, 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-β-d-glucopyronuronate ([(18)F]FEAnGA), was recently developed for PET imaging of extracellular β-glucuronidase (β-GUS). However, [(18)F]FEAnGA exhibited rapid renal clearance, which resulted in a relatively low tracer uptake in the tumor. To improve the pharmacokinetics of [(18)F]FEAnGA, we developed its more lipophilic methyl ester analog, [(18)F]FEAnGA-Me. [(18)F]FEAnGA-Me was obtained by alkylation of the O-protected glucuronide methyl ester precursor with [(18)F]-fluoroethylamine ([(18)F]FEA), followed by removal of the acetate protecting groups with NaOMe/MeOH. The PET tracer was evaluated by in vitro and in vivo studies. [(18)F]FEAnGA-Me was obtained in 5%-10% overall radiochemical yield. It is 10-fold less hydrophilic than [(18)F]FEAnGA and it is stable in PBS and in the presence of β-GUS for 1 h. However, in the presence of esterase or plasma [(18)F]FEAnGA-Me is converted to [(18)F]FEAnGA, and subsequently converted to [(18)F]FEA by β-GUS. MicroPET studies in Wistar rats bearing a C6 glioma and a sterile inflammation showed similar uptake in tumors after injection of either [(18)F]FEAnGA-Me or [(18)F]FEAnGA. Both tracers had a rapid two-phase clearance of total plasma radioactivity with a half-life of 1 and 8 min. The [(18)F]FEAnGA fraction generated from [(18)F]FEAnGA-Me by in vivo hydrolysis had a circulation half-life of 1 and 11 min in plasma. Similar distribution volume in the viable part of the tumor was found after injection of either [(18)F]FEAnGA-Me or [(18)F]FEAnGA. The imaging properties of [(18)F]FEAnGA-Me were not significantly better than those of [(18)F]FEAnGA. Therefore, other strategies should be applied in order to improve the kinetics of these tracers. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Diagnosis of glioma recurrence using multiparametric dynamic 18F-fluoroethyl-tyrosine PET-MRI.

    PubMed

    Pyka, Thomas; Hiob, Daniela; Preibisch, Christine; Gempt, Jens; Wiestler, Benedikt; Schlegel, Jürgen; Straube, Christoph; Zimmer, Claus

    2018-06-01

    To investigate the value of combined 18F-fluorethyltyrosine-(FET)-PET/MRI for differentiation between recurrence and treatment-related changes in glioma patients. 63 lesions suggestive of recurrence in 47 glioma patients were retrospectively identified. All patients had a dynamic FET scan, as well as morphologic MRI, PWI and DWI on a hybrid PET/MRI scanner. Lesions suggestive of recurrence were marked. ROC analysis was performed univariately and on parameter combination. 50 lesions were classified as recurrence, 13 as radiation necrosis. Diagnosis was based on histology in 23 and follow-up imaging in 40 cases. Sensitivities and specificities for static PET were 80 and 85%, 66% and 77% for PWI, 62 and 77% for DWI and 64 and 79% for PET time-to-peak. AUC was 0.86 (p < 0.001) for static PET, 0.73 (p = 0.013) for PWI, 0.70 (p = 0.030) for DWI and 0.73 (p < 0.001) for dynamic PET. Multiparametric analysis resulted in an AUC of 0.89, notably yielding sensitivity of 76% vs. 56% for PET alone at 100% specificity. Simultaneous dynamic FET-PET/MRI was reliably feasible for imaging of recurrent glioma. While all modalities were able to discriminate between recurrence and treatment-related changes, multiparametric analysis added value especially when high specificity was demanded. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

    PubMed

    Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

    2017-03-01

    The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. [18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches.

    PubMed

    de Jong, Evelyn E C; van Elmpt, Wouter; Leijenaar, Ralph T H; Hoekstra, Otto S; Groen, Harry J M; Smit, Egbert F; Boellaard, Ronald; van der Noort, Vincent; Troost, Esther G C; Lambin, Philippe; Dingemans, Anne-Marie C

    2017-01-01

    Nitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival. A total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG. A 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159-0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively). The decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment

  7. Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent.

    PubMed

    Plyku, Donika; Mena, Esther; Rowe, Steven P; Lodge, Martin A; Szabo, Zsolt; Cho, Steve Y; Pomper, Martin G; Sgouros, George; Hobbs, Robert F

    2018-06-01

    Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18 F-DCFPyL in nine patients with metastatic prostate cancer. Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of 18 F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes. The highest calculated mean AD per unit administered activity of 18 F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18 F-DCFPyL was 0.017 ± 0.002 mSv/MBq. 18 F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre

  8. Depicting changes in tumor biology in response to cetuximab mono- or combination therapy by apoptosis and proliferation imaging using 18F-ICMT-11 and 3'-Deoxy-3'-[18F]Fluorothymidine (18F-FLT) PET.

    PubMed

    Heinzmann, Kathrin; Nguyen, Quang-De; Honess, Davina Jean; Smith, Donna-Michelle; Stribbling, Stephen; Brickute, Diana; Barnes, Christopher; Griffiths, John Richard; Aboagye, Eric Ofori

    2018-05-24

    Imaging biomarkers must demonstrate their value in monitoring treatment. Two PET tracers, the caspase-3/7-specific isatin-5-sulfonamide 18 F-ICMT-11 and 3'-Deoxy-3'-[ 18 F]Fluorothymidine ( 18 F-FLT), were employed to detect early treatment-induced changes in tumor biology and whether any changes indicate response to cetuximab, administered as mono- or combination therapy with gemcitabine. Methods: Effects of single or repeated doses of the anti-Epidermal Growth Factor Receptor (EGFR) antibody cetuximab (10mg/kg on day 1 only or day 1 and 2) and/or a single dose of gemcitabine (125mg/kg; day 2) were investigated in mice bearing cetuximab-sensitive H1975 tumors (non-small cell lung cancer) by 18 F-ICMT-11 or 18 F-FLT-PET (day 3). Imaging was also performed in mice bearing cetuximab-insensitive HCT116 tumors (colorectal cancer) after two doses of cetuximab (day 1 and 2). For imaging/histology comparison, tumors were evaluated for proliferation (Ki67; thymidine kinase 1, TK1), cell death (cleaved caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)) and target engagement (EGFR expression) by immunohistochemistry, immunofluorescence and immunoblot, respectively. Tumor and plasma were analysed for thymidine and gemcitabine metabolites by liquid chromatography-mass spectrometry. Results: Retention of both tracers was sensitive to cetuximab in H1975 tumors. 18 F-ICMT-11 uptake and ex vivo cleaved caspase-3 staining notably increased in tumors treated with repeated doses of cetuximab- (75%) and combination-treatment (46%). While one dose of cetuximab was insufficient to induce apoptosis it did affect proliferation. Significant reduction in tumor 18 F-FLT uptake (44 to 50%; P < 0.001) induced by cetuximab mono- and combination-therapy were paralleled with a clear decrease in proliferation (%Ki67 decrease: 72 to 95%; P < 0.0001) and followed by marked tumor growth delay. TK1 expression and tumor thymidine concentrations were profoundly

  9. T156. IN VIVO CHARACTERIZATION OF THE FIRST AGONIST DOPAMINE D1 RECEPTORS PET IMAGING TRACER [18F]MNI-968 IN HUMAN

    PubMed Central

    Tamagnan, Gilles; Barret, Olivier; Alagille, David; Carroll, Vincent; Madonia, Jennifer; Constantinescu, Cristian; SanDiego, Christine; Papin, Caroline; Morley, Thomas; Russell, David; McCarthy, Timothy; Zhang, Lei; Gray, David; Villalobos, Anna; Lee, Chewah; Chen, Jianqing; Seibyl, John; Marek, Kenneth

    2018-01-01

    Abstract Background D1 receptors, which couple to inhibitory G-proteins, have been shown to regulate neuronal growth and development, mediate some behavioral responses. Its function has been shown to be altered in both neurologic and psychiatric disorders. To date, there is a lack of agonist PET tracers for the D1 receptors labeled with 18F with relevance in clinical studies. We report the evaluation in non-human primates of [18F]MNI-968 (PF-06730110), a novel PET radiotracer of the D1 receptors Methods Four brain PET studies, 2 baselines and 2 blockade studies using PF-2562, a D1 partial agonist compound, were conducted for 90 min in two rhesus monkeys with [18F]MNI-968 (169 ± 31 MBq). [18F]PF-06730110 was administered at the same dose level for both monkeys as a bolus followed by a 2-hour infusion, with [18F]MNI-968 administered 30 min into the infusion. Additionally, six brain PET studies were conducted over 180 min (317 ± 49 MBq) in 6 healthy human volunteers (3 test/retest and 3 test). PET data were modeled with 2-tissue compartmental model (2T), Logan graphical analysis (LGA), and non-invasive Logan graphical analysis (NI-LGA) with cerebellar cortex as reference region to estimate total distribution volume VT, and binding potential BPND. For the blockade studies in rhesus monkeys, occupancy was estimated from BPND at baseline and post blockade. Results In rhesus monkeys, [18F]MNI-968 (PF-06730110), penetrated the brain with a peak whole-brain uptake up to ~3% of the injected dose at ~ 6 min post injection and showed a fast washout. The highest signal was found in the caudate, putamen, with moderate extrastriatal uptake. The lowest signal was in the cerebellum. BPND values were up to ~1.4 in the putamen. All three quantification methods (2T, LGA and NI-LGA) were in excellent agreement, with a similar estimated D1 receptors occupancy of PF-06730110 of ~40% for both monkeys in the caudate and putamen. In human, [18F]MNI-968 kinetics appeared to be faster

  10. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET.

    PubMed

    Tixier, Florent; Hatt, Mathieu; Le Rest, Catherine Cheze; Le Pogam, Adrien; Corcos, Laurent; Visvikis, Dimitris

    2012-05-01

    (18)F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Double baseline (18)F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland-Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of -2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of -22.5% to 3.1% and -1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these (18)F-FDG PET-derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.

  11. Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

    PubMed

    Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

    2012-06-01

    Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P < 0.05) and tissue iNOS (P < 0.0001) were higher in patients exhibiting rejection than in those without rejection. Moreover, the (18)F-NOS AUMC at 10 min correlated positively with tissue iNOS at 10 min (R(2) = 0.42, P < 0.05). (18)F-NOS activity was cleared by the hepatobiliary system. The critical organ was the bladder wall, with a dose of 95.3 μGy/MBq, and an effective dose of 15.9 μSv/MBq was calculated. Myocardial (18)F

  12. Direct comparison of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle.

    PubMed

    Nilica, Bernhard; Waitz, Dietmar; Stevanovic, Vlado; Uprimny, Christian; Kendler, Dorota; Buxbaum, Sabine; Warwitz, Boris; Gerardo, Llanos; Henninger, Benjamin; Virgolini, Irene; Rodrigues, Margarida

    2016-08-01

    To determine the value of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined (68)Ga-DOTA-TOC and (18)F-FDG PET/CT studies. (68)Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. (18)F-FDG PET/CT was done within 2 months of (68)Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months). All patients were (68)Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 (18)F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were (18)F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were (18)F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were (18)F-FDG-negative initially but (18)F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were (18)F-FDG-positive initially but (18)F-FDG-negative during follow-up (group 4).(18)F-FDG PET showed more and/or larger metastases than (68)Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation. In NET patients, the presence of (18)F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with (18)F-FDG-negative NET may show (18)F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have (18)F-FDG-positive tumours. Therefore, (18)F-FDG PET/CT is a complementary tool to (68)Ga-DOTA-TOC PET/CT with clinical

  13. Correlation of 6-18F-fluoro-L-dopa PET uptake with proliferation and tumor grade in newly diagnosed and recurrent gliomas.

    PubMed

    Fueger, Barbara J; Czernin, Johannes; Cloughesy, Timothy; Silverman, Daniel H; Geist, Cheri L; Walter, Martin A; Schiepers, Christiaan; Nghiemphu, Phioanh; Lai, Albert; Phelps, Michael E; Chen, Wei

    2010-10-01

    6-(18)F-fluoro-l-dopa ((18)F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of (18)F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. Fifty-nine patients (40 men, 19 women; mean age ± SD, 44.4 ± 12.3 y) with newly diagnosed (n = 22) or recurrent (n = 37) gliomas underwent (18)F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor (18)F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor-to-normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. Fifty-nine lesions in 59 patients were analyzed. (18)F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 ± 1.30 vs. 2.34 ± 1.35, P = 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 ± 1.26 vs. 2.67 ± 1.18, P = 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). (18)F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r = 0.66, P = 0.001) but not in recurrent tumors (r = 0.14, P = 0.41). (18)F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between (18)F-FDOPA uptake and tumor proliferation in newly diagnosed tumors

  14. PET/CT with 18F Fluorocholine as an Imaging Biomarker for Chronic Liver Disease: A Preliminary Radiopathologic Correspondence Study in Patients with Liver Cancer.

    PubMed

    Kwee, Sandi A; Wong, Linda; Chan, Owen T M; Kalathil, Sumodh; Tsai, Naoky

    2018-04-01

    Purpose To determine the relationship between hepatic uptake at preoperative fluorine 18 ( 18 F) fluorocholine combined positron emission tomography (PET) and computed tomography (CT) and the histopathologic features of chronic liver disease in patients with Child-Pugh class A or B disease who are undergoing hepatic resection for liver cancer. Materials and Methods Forty-eight patients with resectable liver tumors underwent preoperative 18 F fluorocholine PET/CT. Mean liver standardized uptake value (SUV mean ) measurements were obtained from PET images, while histologic indexes of inflammation and fibrosis were applied to nontumor liver tissue from resection specimens. Effects of histopathologic features on liver SUV mean were examined with analysis of variance. Results Liver SUV mean ranged from 4.3 to 11.6, correlating significantly with Knodell histologic activity index (ρ = -0.81, P < .001) and several clinical indexes of liver disease severity. Liver SUV mean also differed significantly across groups stratified by necroinflammatory severity and Metavir fibrosis stage (P < . 001). The area under the receiver operating characteristic curve for 18 F fluorocholine PET/CT detecting Metavir fibrosis stage F1 or higher was 0.89 ± 0.05, with an odds-ratio of 3.03 (95% confidence interval: 1.59, 5.88) and sensitivity and specificity of 82% and 93%, respectively. Conclusion Correlations found in patients undergoing hepatic resection for liver cancer between liver 18 F fluorocholine uptake and histopathologic indexes of liver fibrosis and inflammation support the use of 18 F fluorocholine PET/CT as a potential imaging biomarker for chronic liver disease. © RSNA, 2018.

  15. TU-AB-BRA-05: Repeatability of [F-18]-NaF PET Imaging Biomarkers for Bone Lesions: A Multicenter Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, C; Bradshaw, T; Perk, T

    2015-06-15

    Purpose: Quantifying the repeatability of imaging biomarkers is critical for assessing therapeutic response. While therapeutic efficacy has been traditionally quantified by SUV metrics, imaging texture features have shown potential for use as quantitative biomarkers. In this study we evaluated the repeatability of quantitative {sup 18}F-NaF PET-derived SUV metrics and texture features in bone lesions from patients in a multicenter study. Methods: Twenty-nine metastatic castrate-resistant prostate cancer patients received whole-body test-retest NaF PET/CT scans from one of three harmonized imaging centers. Bone lesions of volume greater than 1.5 cm{sup 3} were identified and automatically segmented using a SUV>15 threshold. From eachmore » lesion, 55 NaF PET-derived texture features (including first-order, co-occurrence, grey-level run-length, neighbor gray-level, and neighbor gray-tone difference matrix) were extracted. The test-retest repeatability of each SUV metric and texture feature was assessed with Bland-Altman analysis. Results: A total of 315 bone lesions were evaluated. Of the traditional SUV metrics, the repeatability coefficient (RC) was 12.6 SUV for SUVmax, 2.5 SUV for SUVmean, and 4.3 cm{sup 3} for volume. Their respective intralesion coefficients of variation (COVs) were 12%, 17%, and 6%. Of the texture features, COV was lowest for entropy (0.03%) and highest for kurtosis (105%). Lesion intraclass correlation coefficient (ICC) was lowest for maximum correlation coefficient (ICC=0.848), and highest for entropy (ICC=0.985). Across imaging centers, repeatability of texture features and SUV varied. For example, across imaging centers, COV for SUVmax ranged between 11–23%. Conclusion: Many NaF PET-derived SUV metrics and texture features for bone lesions demonstrated high repeatability, such as SUVmax, entropy, and volume. Several imaging texture features demonstrated poor repeatability, such as SUVtotal and SUVstd. These results can be used to

  16. Spectrum of the Breast Lesions With Increased 18F-FDG Uptake on PET/CT

    PubMed Central

    Dong, Aisheng; Wang, Yang; Lu, Jianping; Zuo, Changjing

    2016-01-01

    Abstract Interpretation of 18F-FDG PET/CT studies in breast is challenging owing to nonspecific FDG uptake in various benign and malignant conditions. Benign conditions include breast changes in pregnancy and lactation, gynecomastia, mastitis, fat necrosis, fibroadenoma, intraductal papilloma, and atypical ductal hyperplasia. Among malignancies, invasive ductal carcinoma and invasive lobular carcinoma are common histological types of breast carcinoma. Rarely, other unusual histological types of breast carcinomas (eg, intraductal papillary carcinoma, invasive micropapillary carcinoma, medullary carcinoma, mucinous carcinoma, and metaplastic carcinoma), lymphoma, and metastasis can be the causes. Knowledge of a wide spectrum of hypermetabolic breast lesions on FDG PET/CT is essential in accurate reading of FDG PET/CT. The purpose of this atlas article is to demonstrate features of various breast lesions encountered at our institution, both benign and malignant, which can result in hypermetabolism on FDG PET/CT imaging. PMID:26975010

  17. Visualizing Nerve Injury in a Neuropathic Pain Model with [18F]FTC-146 PET/MRI.

    PubMed

    Shen, Bin; Behera, Deepak; James, Michelle L; Reyes, Samantha T; Andrews, Lauren; Cipriano, Peter W; Klukinov, Michael; Lutz, Amanda Brosius; Mavlyutov, Timur; Rosenberg, Jarrett; Ruoho, Arnold E; McCurdy, Christopher R; Gambhir, Sanjiv S; Yeomans, David C; Biswal, Sandip; Chin, Frederick T

    2017-01-01

    The ability to locate nerve injury and ensuing neuroinflammation would have tremendous clinical value for improving both the diagnosis and subsequent management of patients suffering from pain, weakness, and other neurologic phenomena associated with peripheral nerve injury. Although several non-invasive techniques exist for assessing the clinical manifestations and morphological aspects of nerve injury, they often fail to provide accurate diagnoses due to limited specificity and/or sensitivity. Herein, we describe a new imaging strategy for visualizing a molecular biomarker of nerve injury/neuroinflammation, i.e. , the sigma-1 receptor (S1R), in a rat model of nerve injury and neuropathic pain. The two-fold higher increase of S1Rs was shown in the injured compared to the uninjured nerve by Western blotting analyses. With our novel S1R-selective radioligand, [ 18 F]FTC-146 (6-(3-[ 18 F]fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[ d ]thiazol-2(3H)-one), and positron emission tomography-magnetic resonance imaging (PET/MRI), we could accurately locate the site of nerve injury created in the rat model. We verified the accuracy of this technique by ex vivo autoradiography and immunostaining, which demonstrated a strong correlation between accumulation of [ 18 F]FTC-146 and S1R staining. Finally, pain relief could also be achieved by blocking S1Rs in the neuroma with local administration of non-radioactive [ 19 F]FTC-146. In summary, [ 18 F]FTC-146 S1R PET/MR imaging has the potential to impact how we diagnose, manage and treat patients with nerve injury, and thus warrants further investigation.

  18. An exploratory study of volumetric analysis for assessing tumor response with (18)F-FAZA PET/CT in patients with advanced non-small-cell lung cancer (NSCLC).

    PubMed

    Kerner, Gerald S M A; Bollineni, Vikram R; Hiltermann, Thijo J N; Sijtsema, Nanna M; Fischer, Alexander; Bongaerts, Alphons H H; Pruim, Jan; Groen, Harry J M

    2016-12-01

    Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as (18)F-fluoroazomycin arabinoside ((18)F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG). The purpose of this study was to study the effects of chemotherapy on (18)F-FAZA and (18)F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients At baseline and after the second chemotherapy cycle, both PET/CT with (18)F-FDG and (18)F-FAZA was performed in seven patients with metastasized NSCLC. (18)F-FAZA and (18)F-FDG scans were aligned with deformable image registration using Mirada DBx. The primary tumors were contoured, and on the (18)F-FDG scan, volumes of interest (VOI) were drawn using a 41 % adaptive threshold technique. Subsequently, the resulting VOI was transferred to the (18)F-FAZA scan. (18)F-FAZA maximum tumor-to-background (T/Bgmax) ratio and the fractional hypoxic volume (FHV) were assessed. Measurements were corrected for partial volume effects. Finally, a voxel-by-voxel analysis of the primary tumor was performed to assess regional uptake differences. In the primary tumor of all seven patients, median (18)F-FDG standard uptake value (SUVmax) decreased significantly (p = 0.03). There was no significant decrease in (18)F-FAZA uptake as measured with T/Bgmax (p = 0.24) or the FHV (p = 0.35). Additionally, volumetric voxel-by-voxel analysis showed that low hypoxic tumors did not significantly change in hypoxic status between baseline and two cycles of chemotherapy, whereas highly hypoxic tumors did. Individualized volumetric voxel-by-voxel analysis revealed that hypoxia and metabolism were not associated before and after 2 cycles of chemotherapy. Tumor hypoxia and metabolism are independent dynamic events as measured by (18)F-FAZA PET and (18)F

  19. Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

    PubMed

    Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

    2014-10-01

    The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Intervention to lower anxiety of 18F-FDG PET/CT patients by use of audiovisual imagery during the uptake phase before imaging.

    PubMed

    Vogel, Wouter V; Valdés Olmos, Renato A; Tijs, Tim J W; Gillies, Murray F; van Elswijk, Gijs; Vogt, Juergen

    2012-06-01

    Many patients referred for PET suffer from anxiety, possibly affecting the workflow and patient experience. In addition, patient anxiety may affect image quality through uptake of (18)F-FDG in muscles or brown adipose tissue (BAT).This study investigated the effects of a nonpharmacologic intervention-the use of audiovisual imagery in the PET uptake room-on patient anxiety and false-positive uptake of (18)F-FDG (in muscles and BAT). A 2-stage study was conducted on 101 patients. The cohort undergoing the intervention included 51 patients. The first stage (n = 35) included physiologic measurements (cardiovascular activity, muscular activity, skin conductance, and cortisol), a state anxiety questionnaire, and visual evaluation of (18)F-FDG uptake in muscles and BAT; the second stage (n = 66) included only the state anxiety questionnaire and the (18)F-FDG uptake evaluation. Throughout the stay in the uptake room, a significant decrease in overall anxiety was found, together with several other significant changes in patient physiology. In the cohort with audiovisual intervention, however, the decrease in patient anxiety was significantly larger. The cohort with intervention also showed significantly lower (18)F-FDG uptake in BAT but not in muscles. The investigated audiovisual intervention helps to lower patient anxiety in the PET uptake room and can lower false-positive (18)F-FDG uptake in BAT.

  1. 18F-FDG PET-CT pattern in idiopathic normal pressure hydrocephalus.

    PubMed

    Townley, Ryan A; Botha, Hugo; Graff-Radford, Jonathan; Boeve, Bradley F; Petersen, Ronald C; Senjem, Matthew L; Knopman, David S; Lowe, Val; Jack, Clifford R; Jones, David T

    2018-01-01

    Idiopathic normal pressure hydrocephalus (iNPH) is an important and treatable cause of neurologic impairment. Diagnosis is complicated due to symptoms overlapping with other age related disorders. The pathophysiology underlying iNPH is not well understood. We explored FDG-PET abnormalities in iNPH patients in order to determine if FDG-PET may serve as a biomarker to differentiate iNPH from common neurodegenerative disorders. We retrospectively compared 18 F-FDG PET-CT imaging patterns from seven iNPH patients (mean age 74 ± 6 years) to age and sex matched controls, as well as patients diagnosed with clinical Alzheimer's disease dementia (AD), Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD), and behavioral variant frontotemporal dementia (bvFTD). Partial volume corrected and uncorrected images were reviewed separately. Patients with iNPH, when compared to controls, AD, DLB/PDD, and bvFTD, had significant regional hypometabolism in the dorsal striatum, involving the caudate and putamen bilaterally. These results remained highly significant after partial volume correction. In this study, we report a FDG-PET pattern of hypometabolism in iNPH involving the caudate and putamen with preserved cortical metabolism. This pattern may differentiate iNPH from degenerative diseases and has the potential to serve as a biomarker for iNPH in future studies. These findings also further our understanding of the pathophysiology underlying the iNPH clinical presentation.

  2. Development of two fluorine-18 labeled PET radioligands targeting PDE10A and in vivo PET evaluation in nonhuman primates.

    PubMed

    Stepanov, Vladimir; Takano, Akihiro; Nakao, Ryuji; Amini, Nahid; Miura, Shotaro; Hasui, Tomoaki; Kimura, Haruhide; Taniguchi, Takahiko; Halldin, Christer

    2018-02-01

    Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [ 11 C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [ 11 C]T-773. [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were synthesized from the same precursor used for 11 C-labeling of T-773 in a two-step approach via 18 F-fluoromethylation and 18 F-fluoroethylation, respectively, using corresponding deuterated synthons. A total of 12 PET measurements were performed in seven non-human primates. First, baseline PET measurements were performed using High Resolution Research Tomograph system with both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 ; the uptake in whole brain and separate brain regions, as well as the specific binding and tissue ratio between putamen and cerebellum, was examined. Second, baseline and pretreatment PET measurements using MP-10 as the blocker were performed for [ 18 F]FM-T-773-d 2 including arterial blood sampling with radiometabolite analysis in four NHPs. Both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were successfully radiolabeled with an average molar activity of 293 ± 114 GBq/μmol (n=8) for [ 18 F]FM-T-773-d 2 and 209 ± 26 GBq/μmol (n=4) for [ 18 F]FE-T-773-d 4 , and a radiochemical yield of 10% (EOB, n=12, range 3%-16%). Both radioligands displayed high brain uptake (~5.5% of injected radioactivity for [ 18 F]FM-T-773-d 2 and ~3.5% for [ 18 F]FE-T-773-d 4 at the peak) and a fast washout. Specific binding reached maximum within 30 min for [ 18 F]FM-T-773-d 2 and after approximately 45 min for [ 18 F]FE-T-773-d 4 . [ 18 F]FM-T-773-d 2 data fitted well with kinetic compartment models. BP ND values obtained indirectly through compartment models were correlated well with those obtained by SRTM. BP ND calculated with SRTM was 1.0-1.7 in the putamen. The occupancy with 1.8

  3. Staging and follow-up of lacrimal gland carcinomas by 18F-FDG PET/CT imaging.

    PubMed

    Tafti, Bashir Akhavan; Shaba, Wisam; Li, Yuxin; Yevdayev, Ella; Berenji, Gholam Reza

    2012-10-01

    A 74-year-old man with right eye proptosis, diplopia, and orbital discomfort for 3 to 4 months underwent biopsy, the specimen of which showed transitional cell carcinoma of the lacrimal gland. 18F-FDG PET/CT was also performed for staging purposes. Six months after orbital exenteration, a follow-up CT scan demonstrated soft tissue thickening along the nasal bridge but could not differentiate between postsurgical changes and cancer recurrence. A concurrent PET/CT scan did not show any evidence of abnormal metabolic activity, further emphasizing the higher accuracy of PET/CT in staging and restaging of head and neck cancers. An annual follow-up scan was still negative for active disease.

  4. Conformationally Strained trans-Cyclooctene (sTCO) Enables the Rapid Construction of 18F-PET Probes via Tetrazine Ligation

    PubMed Central

    Wang, Mengzhe; Svatunek, Dennis; Rohlfing, Katarina; Liu, Yu; Wang, Hui; Giglio, Ben; Yuan, Hong; Wu, Zhanghong; Li, Zibo; Fox, Joseph

    2016-01-01

    The bioorthogonal reaction between tetrazines and trans-cyclooctenes is a method for the rapid construction of F-18 probes for PET imaging. Described here is a second generation 18F-labeling system based on a conformationally strained trans-cyclooctene (sTCO)—a dienophile that is approximately 2 orders of magnitude more reactive than conventional TCO dienophiles. Starting from a readily prepared tosylate precursor, an 18F labeled sTCO derivative (18F-sTCO) could be synthesized in 29.3 +/- 5.1% isolated yield and with high specific activity. Tetrazine ligation was carried out with a cyclic RGD-conjugate of a diphenyl-s-tetrazine analogue (RGD-Tz) chosen from a diene class with an excellent combination of fast reactivity and stability both for the diene as well as the Diels-Alder adduct. For both the tetrazine and the sTCO, mini-PEG spacers were included to enhance solubility and improve the in vivo distribution profile of the resulting probe. Extremely fast reactivity (up to 2.86 x 105 M-1s-1 at 25 °C in water) has been observed in kinetic studies in the reaction of sTCO with diphenyl-s-tetrazine derivatives. A kinetic study on sTCO diastereomers in 55:45 MeOH:water showed that the syn-diastereomer displayed slightly faster reactivity than the anti-diastereomer. An 18F-sTCO conjugate with RGD-Tz demonstrated prominent and persistent tumor uptake in vivo with good tumor-to-background contrast. Unlike most radiolabeled RGD peptides, the tumor uptake of this PET agent increased from 5.3 +/- 0.2% ID/g at 1 h post injection (p.i.), to 8.9 +/- 0.5% ID/g at 4 h p.i., providing evidence for prolonged blood circulation. These findings suggest that tetrazine ligations employing 18F-sTCO should serve as a powerful and general platform for the rapid construction of peptide or protein derived PET agents. PMID:27162558

  5. Reader Training for the Restaging of Biochemically Recurrent Prostate Cancer Using 18F-Fluciclovine PET/CT.

    PubMed

    Miller, Matthew P; Kostakoglu, Lale; Pryma, Daniel; Yu, Jian Qin; Chau, Albert; Perlman, Eric; Clarke, Bonnie; Rosen, Donald; Ward, Penelope

    2017-10-01

    18 F-Fluciclovine is a novel PET/CT tracer. This blinded image evaluation (BIE) sought to demonstrate that, after limited training, readers naïve to 18 F-fluciclovine could interpret 18 F-fluciclovine images from subjects with biochemically recurrent prostate cancer with acceptable diagnostic performance and reproducibility. The primary objectives were to establish individual readers' diagnostic performance and the overall interpretation (2/3 reader concordance) compared with standard-of-truth data (histopathology or clinical follow-up) and to evaluate interreader reproducibility. Secondary objectives included comparison to the expert reader and assessment of intrareader reproducibility. Methods: 18 F-Fluciclovine PET/CT images ( n = 121) and corresponding standard-of-truth data were collected from 110 subjects at Emory University using a single-time-point static acquisition starting 5 min after injection of approximately 370 MBq of 18 F-fluciclovine. Three readers were trained using standardized interpretation methodology and subsequently evaluated the images in a blinded manner. Analyses were conducted at the lesion, region (prostate, including bed and seminal vesicle, or extraprostatic, including all lymph nodes, bone, or soft-tissue metastasis), and subject level. Results: Lesion-level overall positive predictive value was 70.5%. The readers' positive predictive value and negative predictive value were broadly consistent with each other and with the onsite read. Sensitivity was highest for readers 1 and 2 (68.5% and 63.9%, respectively) whereas specificity was highest for reader 3 (83.6%). Overall, prostate-level sensitivity was high (91.4%), but specificity was moderate (48.7%). Interreader agreement was 94.7%, 74.4%, and 70.3% for the lesion, prostate, and extraprostatic levels, respectively, with associated Fleiss' κ-values of 0.54, 0.50, and 0.57. Intrareader agreement was 97.8%, 96.9%, and 99.1% at the lesion level; 100%, 100%, and 91.7% in the prostate

  6. Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients.

    PubMed

    Hsiao, Ing-Tsung; Weng, Yi-Hsin; Lin, Wey-Yil; Hsieh, Chia-Ju; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Kung, Mei-Ping; Lu, Chin-Song; Lin, Kun-Ju

    2014-04-01

    (99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects. Eighteen subjects (8 HC and 10 PD) were recruited for (99m)Tc-TRODAT-1 SPECT, (18)F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts-1). The nonparametric Mann-Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities. The SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p<0.001), and showed significant different between HC and PD subjects. Of note, the (18)F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to (99m)Tc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from (18)F-AV-133 image as compared to (99m)Tc-TRODAT-1 especially at the substantia nigra region. (18)F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical

  7. Rifaximin suppresses background intestinal 18F-FDG uptake on PET/CT scans.

    PubMed

    Franquet, Elisa; Palmer, Mathew R; Gifford, Anne E; Selen, Daryl J; Chen, Yih-Chieh S; Sedora-Roman, Neda; Joyce, Robin M; Kolodny, Gerald M; Moss, Alan C

    2014-10-01

    Identification of cancer or inflammatory bowel disease in the intestinal tract by PET/computed tomography (CT) imaging can be hampered by physiological uptake of F-fluorodeoxyglucose (F-FDG) in the normal colon. Previous work has localized this F-FDG uptake to the intestinal lumen, predominantly occupied by bacteria. We sought to determine whether pretreatment with an antibiotic could reduce F-FDG uptake in the healthy colon. Thirty patients undergoing restaging PET/CT for nongastrointestinal lymphoma were randomly selected to receive rifaximin 550 mg twice daily for 2 days before their scan (post-rifaximin). Their PET/CT images were compared with those from their prior study (pre-rifaximin). Cecal maximum standard uptake value (SUVmax) and overall colonic F-FDG uptake were compared between scans. All PET/CT images were blindly scored by a radiologist. The same comparison of sequential scans was also undertaken in 30 patients who did not receive antibiotics. Thirty post-rifaximin scans were compared with 30 pre-rifaximin scans in the same patients. SUVmax in the cecum was significantly lower in the patient's post-rifaximin scans than in their pre-rifaximin scans (P=0.002). The percentage of scans with greater than grade 1 colonic F-FDG uptake was significantly lower in the post-rifaximin scans than in the pre-rifaximin scans (P<0.05). In contrast, there was no significant difference in the paired sequential scans from control patients, nor a reduction in the percentage of scans with greater than grade 1 colonic F-FDG uptake. This pilot study shows that treatment with rifaximin for 2 days before PET/CT scanning can significantly reduce physiological F-FDG uptake in the normal colonic lumen.

  8. A high-affinity [ 18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

    DOE PAGES

    Ganguly, Tanushree; Dannoon, Shorouk; Hopkins, Mark R.; ...

    2015-06-09

    Here in this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated. p-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [ 18F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(-) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or withoutmore » blocking agent. The crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [ 18F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(-) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h. In conclusion, we have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [ 18F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa.« less

  9. In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging

    DTIC Science & Technology

    2014-10-01

    Transfer ( CRET ) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging PRINCIPAL INVESTIGATOR: Susan L. Deutscher...SUBTITLE 5a. CONTRACT NUMBER In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer ( CRET ) Multiplexed Optical Imaging for Human...internal illumination via 18F-fluorocholine Cerenkov radiation energy transfer ( CRET ) coupled with TF- and ErbB2/3- molecularly targeted near-infrared

  10. Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches.

    PubMed

    Tegnebratt, Tetyana; Ruge, Elisabeth; Bader, Sabine; Ishii, Nobuya; Aida, Satoshi; Yoshimura, Yasushi; Ooi, Chia-Huey; Lu, Li; Mitsios, Nicholas; Meresse, Valerie; Mulder, Jan; Pawlak, Michael; Venturi, Miro; Tessier, Jean; Stone-Elander, Sharon

    2014-12-01

    Inhibition of mitogen-activated protein kinase (MEK, also known as MAPK2, MAPKK), a key molecule of the Ras/MAPK (mitogen-activated protein kinase) pathway, has shown promising effects on B-raf-mutated and some RAS (rat sarcoma)-activated tumors in clinical trials. The objective of this study is to examine the efficacy of a novel allosteric MEK inhibitor RO4987655 in K-ras-mutated human tumor xenograft models using [(18)F] FDG-PET imaging and proteomics technology. [(18)F] FDG uptake was studied in human lung carcinoma xenografts from day 0 to day 9 of RO4987655 therapy using microPET Focus 120 (CTI Concorde Microsystems, Knoxville, TN, USA). The expression levels of GLUT1 and hexokinase 1 were examined using semi-quantitative fluorescent immunohistochemistry (fIHC). The in vivo effects of RO4987655 on MAPK/PI3K pathway components were assessed by reverse phase protein arrays (RPPA). We have observed modest metabolic decreases in tumor [(18)F] FDG uptake after MEK inhibition by RO4987655 as early as 2 h post-treatment. The greatest [(18)F] FDG decreases were found on day 1, followed by a rebound in [(18)F] FDG uptake on day 3 in parallel with decreasing tumor volumes. Molecular analysis of the tumors by fIHC did not reveal statistically significant correlations of GLUT1 and hexokinase 1 expressions with the [(18)F] FDG changes. RPPA signaling response profiling revealed not only down-regulation of pERK1/2, pMKK4, and pmTOR on day 1 after RO4987655 treatment but also significant up-regulation of pMEK1/2, pMEK2, pC-RAF, and pAKT on day 3. The up-regulation of these markers is interpreted to be indicative of a reactivation of the MAPK and activation of the compensatory PI3K pathway, which can also explain the rebound in [(18)F] FDG uptake following MEK inhibition with RO4987655 in the K-ras-mutated human tumor xenografts. We have performed the first preclinical evaluation of a new MEK inhibitor, RO4987655, using a combination of [(18)F] FDG-PET imaging and molecular

  11. 18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

    PubMed

    Courtois, Audrey; Nusgens, Betty V; Hustinx, Roland; Namur, Gauthier; Gomez, Pierre; Somja, Joan; Defraigne, Jean-Olivier; Delvenne, Philippe; Michel, Jean-Baptiste; Colige, Alain C; Sakalihasan, Natzi

    2013-10-01

    Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC

  12. PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.

    PubMed

    Moriguchi, Sho; Kimura, Yasuyuki; Ichise, Masanori; Arakawa, Ryosuke; Takano, Harumasa; Seki, Chie; Ikoma, Yoko; Takahata, Keisuke; Nagashima, Tomohisa; Yamada, Makiko; Mimura, Masaru; Suhara, Tetsuya

    2017-07-01

    Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, ( S , S )- 11 C-MRB and ( S , S )- 18 F-FMeNER-D 2 , have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with ( S , S )- 11 C-MRB and defluorination with ( S , S )- 18 F-FMeNER-D 2 , which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18 F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using ( S , S )- 18 F-FMeNER-D 2 PET. Methods: We analyzed our previous ( S , S )- 18 F-FMeNER-D 2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of ( S , S )- 18 F-FMeNER-D 2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established

  13. 18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.

    PubMed

    Thenkondar, Anuradha; Jafari, Lida; Sooriash, Robbie; Hajsadeghi, Fereshteh; Berenji, Gholam R; Li, Yuxin

    2017-02-01

    A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared asymptomatic on the day of the study, without any signs indicating stroke. Patient also had no known history of malignancy or cerebrovascular disease. He had mild elevation of the prostate-specific antigen level, and biopsy of his prostate was not performed. Patient had long-standing history of chronic back pain and abdominal pain. The PET bone scan demonstrated a large area of very intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke in the same area.

  14. Method for selective recovery of PET-usable quantities of [.sup.18 F] fluoride and [.sup.13 N] nitrate/nitrite from a single irradiation of low-enriched [.sup.18 O] water

    DOEpatents

    Ferrieri, Richard A.; Schlyer, David J.; Shea, Colleen

    1995-06-13

    A process for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- for radiotracer synthesis is disclosed. The process includes producing [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- simultaneously by exposing a low-enriched (20%-30%) [.sup.18 O]H.sub.2 O target to proton irradiation, sequentially isolating the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [.sup.18 F]F.sup.- from the [.sup.18 O]H.sub.2 O target, and reducing the [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- to [.sup.13 N]NH.sub.3. The [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [.sup.18 O]H.sub.2 O, and sequential elution of [.sup.13 N]NO.sub.2.sup.- /NO.sub.3.sup.- and [ .sup.18 F]F.sup.- fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [.sup.13 N]NH.sub.3 and [.sup.18 F]F.sup.- from a single irradiation of a single low-enriched [.sup.18 O]H.sub.2 O target.

  15. Cellular Origin of [18F]FDG-PET Imaging Signals During Ceftriaxone-Stimulated Glutamate Uptake: Astrocytes and Neurons.

    PubMed

    Dienel, Gerald A; Behar, Kevin L; Rothman, Douglas L

    2017-12-01

    Ceftriaxone stimulates astrocytic uptake of the excitatory neurotransmitter glutamate, and it is used to treat glutamatergic excitotoxicity that becomes manifest during many brain diseases. Ceftriaxone-stimulated glutamate transport was reported to drive signals underlying [ 18 F]fluorodeoxyglucose-positron emission tomographic ([ 18 F]FDG-PET) metabolic images of brain glucose utilization and interpreted as supportive of the notion of lactate shuttling from astrocytes to neurons. This study draws attention to critical roles of astrocytes in the energetics and imaging of brain activity, but the results are provocative because (1) the method does not have cellular resolution or provide information about downstream pathways of glucose metabolism, (2) neuronal and astrocytic [ 18 F]FDG uptake were not separately measured, and (3) strong evidence against lactate shuttling was not discussed. Evaluation of potential metabolic responses to ceftriaxone suggests lack of astrocytic specificity and significant contributions by pre- and postsynaptic neuronal compartments. Indeed, astrocytic glycolysis may not make a strong contribution to the [ 18 F]FDG-PET signal because partial or complete oxidation of one glutamate molecule on its uptake generates enough ATP to fuel uptake of 3 to 10 more glutamate molecules, diminishing reliance on glycolysis. The influence of ceftriaxone on energetics of glutamate-glutamine cycling must be determined in astrocytes and neurons to elucidate its roles in excitotoxicity treatment.

  16. A risk-adapted approach using US features and FNA results in the management of thyroid incidentalomas identified by 18F-FDG PET.

    PubMed

    Choi, J S; Choi, Y- J; Kim, E K; Yoon, J H; Youk, J H; Han, K H; Moon, H J; Kang, W J; Kwak, J Y

    2014-02-01

    To assess the risk of malignancy of thyroid incidentalomas found on 18F-FDG PET/CT by US features and cytologic results, and to evaluate the clinical usage of a combination of US features and cytology for post-FNA management of thyroid incidentalomas on 18F-FDG PET/CT. From September 2006 to December 2008, 132 patients with 134 thyroid incidentalomas detected on 18F-FDG PET/CT who had undergone US and US-FNA were included in this study. We evaluated the malignancy rate of thyroid incidentalomas in different subgroups subdivided by US features and US-FNA cytology results. Several variables were compared between the benign and malignant group. The risk of malignancy was 58.2 % (78/132) in thyroid incidentalomas on 18F-FDG PET/CT. Age, gender, and tumor size were not significantly different between the malignant and benign group.  Malignancy rate of thyroid incidentalomas was significantly higher in the suspicious malignant (88.9 %) than in the probably benign group (11.3 %) on US (p < 0.001). Malignancy rates were high in thyroid nodules with "malignancy", "suspicious for malignancy", or "follicular neoplasm" on cytologic results, regardless of US features. However, malignancy rates of thyroid incidentalomas with "unsatisfactory" or "benign" results on cytology were higher in the suspicious malignant (75 %, 12.5 %, respectively) than in the probably benign (0 %) group on US.  This study demonstrated that the risk of malignancy was high in thyroid incidentalomas on 18F-FDG PET/CT even without suspicious US features. However, there was no malignancy in nodules with no suspicious US features and benign cytology. Based on these results, we concluded that US may not replace FNA in the diagnosis of PET incidentalomas, and that a follow-up may be considered of thyroid incidentalomas with benign cytology and no suspicious US features. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Is (18)F-FDG PET really a promising marker for clinically relevant atherosclerosis?

    PubMed

    Brammen, Lindsay; Palumbo, Barbara; Lupattelli, Graziana; Sinzinger, Helmut

    2014-01-01

    Bural et al (2013), retrospectively investigated 143 subjects who received whole body fluorine-18-fluorodeoxyglucose- positron emission tomography ((18)F-FDG-PET) imaging for the assessment of non-cardiovascular diseases. They reported an increase of (18)F-FDG-positive lesions in various aortic segments, which increased with age, and were more pronounced in subjects being aged below 50 years as compared to those above 50. Bural et al also found the highest segmental (18)F-FDG-uptake in the descending thoracic aorta, but not in the abdominal aorta, where the majority of the most severe atherosclerotic lesions essentially appear. In addition, they did not appreciate any significant gender difference. Despite the severe limitation that no correlation to vascular disease, risk factors, or any clinical parameter was available, this report again raises the question as to what positive (18)F-FDG imaging really reflects and whether it will ever reach the great expectations. Conventional radiotracers revealed an excellent experimental correlation, as well as morphology. Uptake ratios of symptomatic lesion vs. contralateral unaffected side were comparable between (111)In-platelets, (123)I-LDL and (18)FFDG. There was also a mass strategic correlation, but no individual prediction of events at all. Due to better statistics, image quality and solution PET imaging of atherosclerosis holds great promise. However, correlations between various tracers and vascular wall characteristics (and staining methodologies) in 1% cholesterol fed rabbits reveal that (18)F-FDG is not always the best tracer. Vascular foam cell content is reflected by (111)In-HIG > (125)I-oxLp(a) > (18)F-FDG > (125)I-LDL (Brammen L, Palumbo B, Lupattelli G et al. Unpublished data). A close correlation to Framingham risk score is for example not helpful, as this score has a low predictive value of only 0.6. The available clinical correlations between (18)F-FDG-uptake and arterial wall characteristics are poor. For

  18. Post-therapy lesions in patients with non-Hodgkin's lymphoma characterized by 18F-FDG PET/CT-guided biopsy using automated robotic biopsy arm.

    PubMed

    Radhakrishnan, Renjith K; Mittal, Bhagwant R; Basher, Rajender K; Prakash, Gaurav; Malhotra, Pankaj; Kalra, Naveen; Das, Ashim

    2018-01-01

    The aim of this study was to analyse the positive predictive value (PPV) of post-therapy fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT performed for response or recurrence evaluation in patients with non-Hodgkin's lymphoma (NHL) and to appraise the diagnostic utility of F-FDG PET/CT-guided biopsy in this setting. A total of 17 patients with NHL showing F-FDG avid lesions in F-FDG PET/CT performed for response or recurrence assessment underwent F-FDG PET/CT-guided biopsy using automated robotic biopsy arm needle navigation technique. The objectives were analysed in reference to histopathology. In all, 15 of the 17 (88.5%) procedures yielded adequate representative tissue samples. Nine out of 15 lesions were positive for residual disease and the remaining revealed benign findings on histopathology. One patient with inconclusive biopsy underwent surgical resection and histopathology confirmed the presence of residual disease. PPV of theF-FDG PET/CT was observed to be 62.5% (10/16). F-FDG PET/CT for response evaluation in NHL possesses a low PPV and hence warrants histopathological correlation when F-FDG PET/CT findings influence management decision. Diagnostic yield of F-FDG PET/CT-guided biopsy is high and has the potential to reduce sampling errors.

  19. 18F-FDG labeling of mesenchymal stem cells and multipotent adult progenitor cells for PET imaging: effects on ultrastructure and differentiation capacity.

    PubMed

    Wolfs, Esther; Struys, Tom; Notelaers, Tineke; Roberts, Scott J; Sohni, Abhishek; Bormans, Guy; Van Laere, Koen; Luyten, Frank P; Gheysens, Olivier; Lambrichts, Ivo; Verfaillie, Catherine M; Deroose, Christophe M

    2013-03-01

    Because of their extended differentiation capacity, stem cells have gained great interest in the field of regenerative medicine. For the development of therapeutic strategies, more knowledge on the in vivo fate of these cells has to be acquired. Therefore, stem cells can be labeled with radioactive tracer molecules such as (18)F-FDG, a positron-emitting glucose analog that is taken up and metabolically trapped by the cells. The aim of this study was to optimize the radioactive labeling of mesenchymal stem cells (MSCs) and multipotent adult progenitor cells (MAPCs) in vitro with (18)F-FDG and to investigate the potential radiotoxic effects of this labeling procedure with a range of techniques, including transmission electron microscopy (TEM). Mouse MSCs and rat MAPCs were used for (18)F-FDG uptake kinetics and tracer retention studies. Cell metabolic activity, proliferation, differentiation and ultrastructural changes after labeling were evaluated using an Alamar Blue reagent, doubling time calculations and quantitative TEM, respectively. Additionally, mice were injected with MSCs and MAPCs prelabeled with (18)F-FDG, and stem cell biodistribution was investigated using small-animal PET. The optimal incubation period for (18)F-FDG uptake was 60 min. Significant early tracer washout was observed, with approximately 30%-40% of the tracer being retained inside the cells 3 h after labeling. Cell viability, proliferation, and differentiation capacity were not severely affected by (18)F-FDG labeling. No major changes at the ultrastructural level, considering mitochondrial length, lysosome size, the number of lysosomes, the number of vacuoles, and the average rough endoplasmic reticulum width, were observed with TEM. Small-animal PET experiments with radiolabeled MAPCs and MSCs injected intravenously in mice showed a predominant accumulation in the lungs and a substantial elution of (18)F-FDG from the cells. MSCs and MAPCs can be successfully labeled with (18)F-FDG for

  20. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis.

    PubMed

    Evangelista, Laura; Guttilla, Andrea; Zattoni, Fabio; Muzzio, Pier Carlo; Zattoni, Filiberto

    2013-06-01

    Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment. To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa. A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed. From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9-58.4) and pooled specificity 95% (95% CI, 92-97.1). The area under the curve was 0.9446 (p<0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109-50.773). Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted. Copyright © 2012 European Association of Urology. Published by

  1. {sup 18}F-desmethoxyfallypride: A fluorine-18 labeled radiotracer with properties similar to carbon-11 raclopride for PET imaging studies of dopamine D{sub 2} receptors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mukherjee, J.; Yang, Z.Y.; Brown, T.

    1996-07-19

    We have developed (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-{sup 18}F-fluoropropyl)-2-methoxybenzamide ({sup 18}F-desmethoxyfallypride) as a fluorine-18 radiotracer with properties analogous to that of {sup 11}C-raclopride. In vitro experiments in rat brain homogenates showed an association rate constant of 2.1X10{sup 8} M{sup -1} min{sup -1} and a dissociation rate constant of 0.073 min{sup -1}. High striatal uptake (up to 0.08% injected dose/cc) of {sup 18}F-desmethoxyfallypride in rhesus monkeys was observed in PET experiments. The radiotracer cleared from the striata with a dissociation rate of 1.80X10{sup -2} min{sup -1}. Striatum to cerebellum ratios peaked at 3.0 in 30 min after which they decreased steadily. Intravenously administered haloperidol displacedmore » specifically bound {sup 18}F-desmethoxyfallypride with a k{sub off} of 0.058 min{sup -1}. Synaptic dopamine released by the treatment of the monkeys with a d-amphetamine increased the dissociation rate of {sup 18}F-desmethoxyfallypride to 0.83 min{sup -1} thus reducing specifically bound {sup 18}F-desmethoxyfallypride by 56% over a period of 42 mins compared to a reduction of only 20% in controls during this time period. The sensitivity of {sup 18}F-desmethoxyfallypride towards competition with dopamine should make this radiotracer useful in PET studies to evaluate in vivo pharmacological effects of various agents that alter levels of endogenous dopamine. 27 refs., 8 figs.« less

  2. The Incremental Value of Subjective and Quantitative Assessment of 18F-FDG PET for the Prediction of Pathologic Complete Response to Preoperative Chemoradiotherapy in Esophageal Cancer.

    PubMed

    van Rossum, Peter S N; Fried, David V; Zhang, Lifei; Hofstetter, Wayne L; van Vulpen, Marco; Meijer, Gert J; Court, Laurence E; Lin, Steven H

    2016-05-01

    A reliable prediction of a pathologic complete response (pathCR) to chemoradiotherapy before surgery for esophageal cancer would enable investigators to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. So far no clinical parameters or diagnostic studies are able to accurately predict which patients will achieve a pathCR. The aim of this study was to determine whether subjective and quantitative assessment of baseline and postchemoradiation (18)F-FDG PET can improve the accuracy of predicting pathCR to preoperative chemoradiotherapy in esophageal cancer beyond clinical predictors. This retrospective study was approved by the institutional review board, and the need for written informed consent was waived. Clinical parameters along with subjective and quantitative parameters from baseline and postchemoradiation (18)F-FDG PET were derived from 217 esophageal adenocarcinoma patients who underwent chemoradiotherapy followed by surgery. The associations between these parameters and pathCR were studied in univariable and multivariable logistic regression analysis. Four prediction models were constructed and internally validated using bootstrapping to study the incremental predictive values of subjective assessment of (18)F-FDG PET, conventional quantitative metabolic features, and comprehensive (18)F-FDG PET texture/geometry features, respectively. The clinical benefit of (18)F-FDG PET was determined using decision-curve analysis. A pathCR was found in 59 (27%) patients. A clinical prediction model (corrected c-index, 0.67) was improved by adding (18)F-FDG PET-based subjective assessment of response (corrected c-index, 0.72). This latter model was slightly improved by the addition of 1 conventional quantitative metabolic feature only (i.e., postchemoradiation total lesion glycolysis; corrected c-index, 0.73), and even more by subsequently adding 4 comprehensive (18)F-FDG PET texture/geometry features (corrected c-index, 0

  3. PROSPECTIVE EVALUATION OF 18F-FDG UPTAKE IN POST-ISCHEMIC MYOCARDIUM BY SIMULTANEOUS PET/MRI AS A PROGNOSTIC MARKER OF FUNCTIONAL OUTCOME

    PubMed Central

    Rischpler, Christoph; Dirschinger, Ralf J.; Nekolla, Stephan G.; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P.; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

    2016-01-01

    Background The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by 18F-FDG PET/MRI in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI 18F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of 18F-FDG-PET/MRI in patients after AMI as a biosignal for left ventricular functional outcome. Methods and Results We prospectively enrolled 49 patients with STEMI and performed 18F-FDG-PET/MRI 5 days after PCI and follow-up cardiac MRI after 6–9 months. In a subset of patients, 99mTc-sestamibi-SPECT was performed with tracer injection prior to revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of 18F-FDG-uptake and LGE showed substantial overlap (κ=0.66), while quantitative analysis demonstrated that 18F-FDG extent exceeded LGE extent (33.2±16.2 %LV vs. 20.4±10.6 %LV, p<0.0001) and corresponded to the area-at-risk (r=0.87, p<0.0001). The peripheral blood count of CD14high/CD16+ monocytes correlated with the infarction size and 18F-FDG signal extent (r=0.53, p<0.002 and r=0.42, p<0.02, respectively). 18F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar and the SUVmean was associated with left ventricular functional outcome independent of infarct size (ΔEF: p<0.04, ΔEDV: p<0.02, ΔESV: p<0.005). Conclusions In the current study, the intensity of 18F-FDG uptake in the myocardium after AMI correlated inversely with functional outcome at 6 months. Thus, 18F-FDG uptake in infarcted myocardium may represent a novel biosignal of myocardial injury. PMID:27056601

  4. Evaluation of treatment response and resistance in metastatic renal cell cancer (mRCC) using integrated 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI); The REMAP study.

    PubMed

    Kelly-Morland, Christian; Rudman, Sarah; Nathan, Paul; Mallett, Susan; Montana, Giovanni; Cook, Gary; Goh, Vicky

    2017-06-02

    Tyrosine kinase inhibitors are the first line standard of care for treatment of metastatic renal cell carcinoma (RCC). Accurate response assessment in the setting of antiangiogenic therapies remains suboptimal as standard size-related response criteria do not necessarily accurately reflect clinical benefit, as they may be less pronounced or occur later in therapy than devascularisation. The challenge for imaging is providing timely assessment of disease status allowing therapies to be tailored to ensure ongoing clinical benefit. We propose that combined assessment of morphological, physiological and metabolic imaging parameters using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ( 18 F-FDG PET/MRI) will better reflect disease behaviour, improving assessment of response/non-response/relapse. The REMAP study is a single-centre prospective observational study. Eligible patients with metastatic renal cell carcinoma, planned for systemic therapy, with at least 2 lesions will undergo an integrated 18 F-FDG PET and MRI whole body imaging with diffusion weighted and contrast-enhanced multiphasic as well as standard anatomical MRI sequences at baseline, 12 weeks and 24 weeks of systemic therapy allowing 18 F-FDG standardised uptake value (SUV), apparent diffusion co-efficient (ADC) and normalised signal intensity (SI) parameters to be obtained. Standard of care contrast-enhanced computed tomography CT scans will be performed at equivalent time-points. CT response categorisation will be performed using RECIST 1.1 and alternative (modified)Choi and MASS criteria. The reference standard for disease status will be by consensus panel taking into account clinical, biochemical and conventional imaging parameters. Intra- and inter-tumoural heterogeneity in vascular, diffusion and metabolic response/non-response will be assessed by image texture analysis. Imaging will also inform the development of computational methods for automated disease status

  5. Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

    PubMed

    Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

    2017-05-01

    Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion

  6. [18F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple Negative Breast Cancer in Response to Glutaminase Inhibition

    PubMed Central

    Pantel, Austin R.; Li, Shihong; Lieberman, Brian P.; Ploessl, Karl; Choi, Hoon; Blankemeyer, Eric; Lee, Hsiaoju; Kung, Hank F.; Mach, Robert H.

    2017-01-01

    Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution 1H magnetic resonance spectroscopy (MRS). GLS inhibition significantly increased glutamine pool size in TNBC tumors. MCF-7 tumors, with inherently low GLS activity compared to TNBC, displayed a larger baseline glutamine pool size that did not change as much in response to GLS inhibition. The tumor-to-blood-activity-ratios (T/B) obtained from [18F]4F-Gln PET images matched the distinct glutamine pool sizes of both tumor models at baseline. After a short course of GLS inhibitor treatment, the T/B values increased significantly in TNBC, but did not change in MCF-7 tumors. Across both tumor types and after GLS inhibitor or vehicle treatment, we observed a strong positive correlation between T/B values and tumor glutamine pool size measured using MRS (R2=0.71). In conclusion, [18F]4F-Gln PET tracked cellular glutamine pool size in breast cancers with differential GLS activity and detected increases in cellular glutamine pool size induced by GLS inhibitors. This study accomplished the first necessary step towards validating [18F]4F-Gln PET as a PD marker for glutaminase-targeting drugs. PMID:28202527

  7. 18F-FDG positron emission tomography/computed tomography in infective endocarditis.

    PubMed

    Salomäki, Soile Pauliina; Saraste, Antti; Kemppainen, Jukka; Bax, Jeroen J; Knuuti, Juhani; Nuutila, Pirjo; Seppänen, Marko; Roivainen, Anne; Airaksinen, Juhani; Pirilä, Laura; Oksi, Jarmo; Hohenthal, Ulla

    2017-02-01

    The diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in IE. Sixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18 F-FDG-PET/CT. 18 F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUV max ) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference. There was strong, focal 18 F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUV max of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18 F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE. 18 F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

  8. Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan; Kligerman, Seth

    2013-04-01

    Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, andmore » associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.« less

  9. Correcting (18)F-fluoride PET static scan measurements of skeletal plasma clearance for tracer efflux from bone.

    PubMed

    Siddique, Musib; Frost, Michelle L; Moore, Amelia E B; Fogelman, Ignac; Blake, Glen M

    2014-03-01

    The aim of the study was to examine whether (18)F-fluoride PET ((18)F-PET) static scan measurements of bone plasma clearance (Ki) can be corrected for tracer efflux from bone from the time of injection. The efflux of tracer from bone mineral to plasma was described by a first-order rate constant kloss. A modified Patlak analysis was applied to 60-min dynamic (18)F-PET scans of the spine and hip acquired during trials on the bone anabolic agent teriparatide to find the best-fit values of kloss at the lumbar spine, total hip and femoral shaft. The resulting values of kloss were used to extrapolate the modified Patlak plots to 120 min after injection and derive a sequence of static scan estimates of Ki at 4-min intervals that were compared with the Patlak Ki values from the 60-min dynamic scans. A comparison was made with the results of the standard static scan analysis, which assumes kloss=0. The best-fit values of kloss for the spine and hip regions of interest averaged 0.006/min and did not change when patients were treated with teriparatide. Static scan values of Ki calculated using the modified analysis with kloss=0.006/min were independent of time between 10 and 120 min after injection and were in close agreement with findings from the dynamic scans. In contrast, by 2 h after injection the static scan Ki values calculated using the standard analysis underestimated the dynamic scan results by 20%. Using a modified analysis that corrects for F efflux from bone, estimates of Ki from static PET scans can be corrected for time up to 2 h after injection. This simplified approach may obviate the need to perform dynamic scans and hence shorten the scanning procedure for the patient and reduce the cost of studies. It also enables reliable estimates of Ki to be obtained from multiple skeletal sites with a single injection of tracer.

  10. Cerebral 18F-FDG PET in macrophagic myofasciitis: An individual SVM-based approach.

    PubMed

    Blanc-Durand, Paul; Van Der Gucht, Axel; Guedj, Eric; Abulizi, Mukedaisi; Aoun-Sebaiti, Mehdi; Lerman, Lionel; Verger, Antoine; Authier, François-Jérôme; Itti, Emmanuel

    2017-01-01

    Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles. 18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated. The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%. We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts.

  11. Method for selective recovery of PET-usable quantities of [{sup 18}F] fluoride and [{sup 13}N] nitrate/nitrite from a single irradiation of low-enriched [{sup 18}O] water

    DOEpatents

    Ferrieri, R.A.; Schlyer, D.J.; Shea, C.

    1995-06-13

    A process for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} for radiotracer synthesis is disclosed. The process includes producing [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}}and [{sup 18}F]F{sup {minus}} simultaneously by exposing a low-enriched (20%-30%) [{sup 18}O]H{sub 2}O target to proton irradiation, sequentially isolating the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} from the [{sup 18}O]H{sub 2}O target, and reducing the [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} to [{sup 13}N]NH{sub 3}. The [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} products are then conveyed to a laboratory for radiotracer applications. The process employs an anion exchange resin for isolation of the isotopes from the [{sup 18}O]H{sub 2}O, and sequential elution of [{sup 13}N]NO{sub 2}{sup {minus}}/NO{sub 3}{sup {minus}} and [{sup 18}F]F{sup {minus}} fractions. Also the apparatus is disclosed for simultaneously producing PET-usable quantities of [{sup 13}N]NH{sub 3} and [{sup 18}F]F{sup {minus}} from a single irradiation of a single low-enriched [{sup 18}O]H{sub 2}O target. 2 figs.

  12. The Utility of PET/CT in the Planning of External Radiation Therapy for Prostate Cancer.

    PubMed

    Calais, Jeremie; Cao, Minsong; Nickols, Nicholas G

    2018-04-01

    Radiotherapy and radical prostatectomy are the definitive treatment options for patients with localized prostate cancer. A rising level of prostate-specific antigen after radical prostatectomy indicates prostate cancer recurrence, and these patients may still be cured with salvage radiotherapy. To maximize chance for cure, the irradiated volumes should completely encompass the extent of disease. Therefore, accurate estimation of the location of disease is critical for radiotherapy planning in both the definitive and the salvage settings. Current first-line imaging for prostate cancer has limited sensitivity for detection of disease both at initial staging and at biochemical recurrence. Integration of PET into routine evaluation of prostate cancer patients may improve both staging accuracy and radiotherapy planning. 18 F-FDG PET/CT is now routinely used in radiation planning for several cancer types. However, 18 F-FDG PET/CT has low sensitivity for prostate cancer. Additional PET probes evaluated in prostate cancer include 18 F-sodium fluoride, 11 C-acetate, 11 C- or 18 F-choline, 18 F-fluciclovine, and 68 Ga- or 18 F-labeled ligands that bind prostate-specific membrane antigen (PSMA). PSMA ligands appear to be the most sensitive and specific but have not yet received Food and Drug Administration New Drug Application approval for use in the United States. Retrospective and prospective investigations suggest a potential major impact of PET/CT on prostate radiation treatment planning. Prospective trials randomizing patients to routine radiotherapy planning versus PET/CT-aided planning may show meaningful clinical outcomes. Prospective clinical trials evaluating the addition of 18 F-fluciclovine PET/CT for planning of salvage radiotherapy with clinical endpoints are under way. Prospective trials evaluating the clinical impact of PSMA PET/CT on prostate radiation planning are indicated. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  13. The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

    PubMed Central

    Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2013-01-01

    We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

  14. [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - Comparison to [18F]FDG and laboratory values.

    PubMed

    Lapa, Constantin; Schreder, Martin; Schirbel, Andreas; Samnick, Samuel; Kortüm, Klaus Martin; Herrmann, Ken; Kropf, Saskia; Einsele, Herrmann; Buck, Andreas K; Wester, Hans-Jürgen; Knop, Stefan; Lückerath, Katharina

    2017-01-01

    Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [ 68 Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [ 68 Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [ 18 F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [ 68 Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [ 18 F]FDG was available, [ 68 Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [ 18 F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [ 18 F]FDG-PET positivity correlated with [ 68 Ga]Pentixafor-PET positivity (p=0.018). [ 68 Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma.

  15. Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

    PubMed

    Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

    2018-03-12

    Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

  16. Fluorine-18 labeled tracers for PET studies in the neurosciences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, Yu-Shin; Fowler, J.S.

    This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18more » labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.« less

  17. Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

    PubMed

    Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

    2017-05-01

    Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P < .001). Static fuzzy locally adaptive Bayesian (FLAB) volumes corresponded best with pathology volumes (intraclass correlation coefficient, 0.72; P < .001). Bland-Altman analyses showed the highest precision and accuracy for static FLAB volumes. Glucose metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG PET images is in best agreement with pathology volume and could be useful

  18. Development of PEGylated peptide probes conjugated with (18)F-labeled BODIPY for PET/optical imaging of MT1-MMP activity.

    PubMed

    Kondo, Naoya; Temma, Takashi; Deguchi, Jun; Sano, Kohei; Ono, Masahiro; Saji, Hideo

    2015-12-28

    Since the processing activity of the matrix metalloproteinase MT1-MMP regulates various cellular functions such as motility, invasion, growth, differentiation and apoptosis, precise in vivo evaluation of MT1-MMP activity in cancers can provide beneficial information for both basic and clinical studies. For this purpose, we designed a cleavable Positron Emission Tomography (PET)/optical imaging probe consisting of BODIPY650/665 and polyethylene glycol (PEG) conjugated to opposite ends of MT1-MMP substrate peptides. We used in vitro and in vivo fluorescence experiments to select suitable substrate peptide sequences and PEG sizes for the MT1-MMP probes and obtained an optimized structure referred to here as MBP-2k. Radiofluorinated MBP-2k ([(18)F]MBP-2k) was then successfully synthesized via an (18)F-(19)F isotopic exchange reaction in BODIPY650/665. After intravenous injection into mice with xenografted tumors, [(18)F]MBP-2k showed significantly higher accumulation in HT1080 tumors with high MT1-MMP activity than in A549 tumors that have low MT1-MMP activity. Moreover, PET images showed better contrast in HT1080 tumors. These results show that [(18)F]MBP-2k can be used as a hybrid PET/optical imaging agent and is a promising probe for non-invasive monitoring of MT1-MMP activity in cancers. This probe may also efficiently combine targeted tumor imaging with image-guided surgery that could be beneficial for patients in the future. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

    PubMed

    Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

    2017-07-01

    We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

  20. Endoscopic and histopathological analysis of incidental focal colorectal 18 F-fluorodeoxyglucose uptake in PET/CT scan: Colonoscopic evaluation is warranted.

    PubMed

    Valente, Michael A

    2018-03-01

    Unexpected focal colorectal 18  F-fluorodeoxyglucose uptake has become a common clinical dilemma. The aim of this study was to identify the clinical significance of incidentally detected colorectal lesions on PET/CT scans by comparing positive PET/CT findings with endoscopic and histopathological analysis. A retrospective analysis of a colonoscopy database was reviewed. All patients that underwent colonoscopy secondary to focal incidental uptake on PET/CT were evaluated. PET/CT findings were correlated with endoscopic and histopathological results. 84 patients underwent colonoscopy secondary to incidental focal colorectal uptake on PET/CT. A total of 63 patients had an endoscopic and histological confirmation of the area of abnormality, for a positive predictive value of 75%. Newly diagnosed colorectal carcinoma was discovered in 13 patients (15.4%) and forty-four patients (52.3%) were discovered to have a premalignant lesion. Incidental focal colorectal uptake of 18  F-fluorodeoxyglucose is associated with a substantial risk of underlying neoplastic colorectal lesions. Early identification of these lesions may alter patient management and treatment plans. Copyright © 2017 Elsevier Inc. All rights reserved.