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Sample records for 2-18f fluoro-2-desoxy-d-glucose tep-fdg

  1. 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography initial staging impacts on survival in Hodgkin lymphoma

    PubMed Central

    Cerci, Juliano J; Linardi, Camila C G; Pracchia, Luís F; Junior, José Soares; Trindade, Evelinda; Delbeke, Dominique; Cerci, Rodrigo J; Carr, Robert; Meneghetti, José C; Buccheri, Valeria

    2013-01-01

    AIM: To assess the prognostic value and risk classification improvement of metabolic staging (MS) with Initial 2-[18F]-fluoro-2-desoxy-D-glucose positron emission tomography (FDG-PET) in initial staging of Hodgkin’s Lymphoma (HL) patients to predict 5 years overall survival (5y-OS) and event free survival (EFS). METHODS: A total of 275 patients were included in this retrospective study, 155 patients were staged with conventional anatomical staging (AS), and 120 also submitted to MS (FDG-PET). Prognostic analysis compared 5y-OS and 5y-EFS of patients staged with AS and MS. Risk-adjusted models incorporated clinical risk factors, computed tomography and FDG-PET staging. RESULTS: During the follow up of 267 evaluated patients, 220 (122 AS and 98 MS) achieved complete remission after first-line therapy (median follow-up: 70 ± 29 mo), treatment failure occurred in 79 patients and 34 died. The 5y-EFS for early vs advanced disease in AS patients was 79.3% and 66.7%, and 85.6% and 53.6% in MS patients, respectively (P < 0.01). The 5y-OS for early and advanced disease with AS was 91.3% and 81.5%, and 97.5% and 80.7% for patients staged with MS, respectively. Cox proportional hazards analysis demonstrated that FDG-PET added significant prognostic information and improved risk prediction (P = 0.02). CONCLUSION: Initial staging FDG-PET could be used as an accurate and independent predictor of OS and EFS in HL, with impact in 5y-EFS and OS. PMID:24379935

  2. Synthesis of 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline: Aprospective irreversible EGFR binding probe

    SciTech Connect

    Vasdev, Neil; Dorff, Peter N.; Gibbs, Andrew R.; Nandanan,Erathodiyil; Reid, Leanne M.; O'Neil, James P.; VanBrocklin, Henry F.

    2004-03-30

    Acrylamido-quinazolines substituted at the 6-position bindirreversibly to the intracellular ATP binding domain of the epidermalgrowth factor receptor (EGFR). A general route was developed forpreparing 6-substituted-4-anilinoquinazolines from [18F]fluoroanilinesfor evaluation as EGFR targeting agents with PET. By a cyclizationreaction, 2-[18F]fluoroaniline was reacted withN'-(2-cyano-4-nitrophenyl)-N,N-dimethylimidoformamide to produce6-nitro-4-(2-[18F]fluoroanilino)quinazoline in 27.5 percentdecay-corrected radiochemical yield. Acid mediated tin chloride reductionof the nitro group was achieved in 5 min (80 percent conversion) andsubsequent acylation with acrylic acid gave6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline in 8.5 percentdecay-corrected radiochemical yield, from starting fluoride, in less than2 hours.

  3. Synthesis and biological evaluation of anti-1-amino-2-[18F]fluoro-cyclobutyl-1-carboxylic acid (anti-2-[18F]FACBC) in rat 9L gliosarcoma.

    PubMed

    Yu, Weiping; Williams, Larry; Camp, Vernon M; Olson, Jeffrey J; Goodman, Mark M

    2010-04-01

    A new [(18)F] labeled amino acid anti-1-amino-2-[(18)F]fluoro-cyclobutyl-1-carboxylic acid 9 (anti-2-[(18)F]FACBC) was synthesized in 30% decay-corrected yield with high radiochemical purity over 99%. The cyclic sulfamidate precursor was very stable and highly reactive towards nucleophilic radiofluorination. Cell uptake assays with rat 9L gliosarcoma cells showed that [(18)F]9 was transported into tumor cells via multiple amino acid transport systems, including L and A systems. Biodistribution study in rats with intracranial 9L gliosarcoma tumors demonstrated that [(18)F]9 had a rapid and prolonged accumulation in tumors with 26:1 tumor to brain ratio at 120 min post-injection. In this model, [(18)F]9 is a potential PET tracer for brain tumor imaging.

  4. Facile purification and click labeling with 2-[18F]fluoroethyl azide using solid phase extraction cartridges

    DOE PAGES

    Zhou, Dong; Chu, Wenhua; Peng, Xin; ...

    2014-11-04

    In this paper, a facile method was developed to purify 2-[18F]fluoroethyl azide ([18F]FEA) using a C18 cartridge and an Oasis® HLB cartridge in series, in which [18F]FEA was exclusively trapped on the HLB cartridge. [18F]FEA can be eluted for reactions in solution; alternatively click labeling can be carried out on the HLB cartridge itself by loading an alkyne substrate and copper (I) catalyst dissolved in DMF onto the cartridge. Finally, this solid phase extraction methodology for purification and click labeling with [18F]FEA, either in solution or on the cartridge, is safe, simple, reproducible in high yield, and compatible with automatedmore » synthesis of 18F-labeled PET tracers.« less

  5. Evaluation of 2-[18F]fluoroacetate kinetics in rodent models of cerebral hypoxia–ischemia

    PubMed Central

    Ouyang, Yu; Tinianow, Jeff N; Cherry, Simon R; Marik, Jan

    2014-01-01

    Glia account for 90% of human brain cells and have a significant role in brain homeostasis. Thus, specific in vivo imaging markers of glial metabolism are potentially valuable. In the brain, 2-fluoroacetate is selectively taken up by glial cells and becomes metabolically trapped in the tricarboxylic acid cycle. Recent work in rodent brain injury models demonstrated elevated lesion uptake of 2-[18F]fluoroacetate ([18F]FACE), suggesting possible use for specifically imaging glial metabolism. To assess this hypothesis, we evaluated [18F]FACE kinetics in rodent models of cerebral hypoxia–ischemia at 3 and 24 hours post insult. Lesion uptake was significantly higher at 30 minutes post injection (P<0.05). An image-based method for input function estimation using cardiac blood was validated. Analysis of whole blood showed no significant metabolites and plasma activity concentrations of ∼50% that of whole blood. Kinetic models describing [18F]FACE uptake were developed and quantitatively compared. Elevated [18F]FACE uptake was found to be driven primarily by K1/k2 rather than k3, but changes in the latter were detectable. The two-tissue irreversible uptake model (2T3k) was found to be necessary and sufficient for modeling [18F]FACE uptake. We conclude that kinetic modeling of [18F]FACE uptake represents a potentially useful tool for interrogation of glial metabolism. PMID:24517980

  6. Characterization of 5-(2- 18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas

    PubMed Central

    Abbas, Ahmed; Beamish, Christine; McGirr, Rebecca; Demarco, John; Cockburn, Neil; Krokowski, Dawid; Lee, Ting-Yim; Kovacs, Michael; Hatzoglou, Maria; Dhanvantari, Savita

    2016-01-01

    Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- 18F-fluoroethoxy)-L-tryptophan ( 18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of 18F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy. Results: Uptake of 18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced 18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in 18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of 18F-L-FEHTP uptake with beta cell mass. Conclusions: 18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore, 18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes. PMID:27909574

  7. 2'[(18)F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function.

    PubMed

    Trencsényi, György; Kertész, István; Krasznai, Zoárd T; Máté, Gábor; Szalóki, Gábor; Szabó Judit, P; Kárpáti, Levente; Krasznai, Zoltán; Márián, Teréz; Goda, Katalin

    2015-07-10

    In vivo detection of the emergence of P-glycoprotein (Pgp) mediated multidrug resistance in tumors could be beneficial for patients treated with anticancer drugs. PET technique in combination with appropriate radiotracers could be the most convenient method for detection of Pgp function. Rhodamine derivatives are validated fluorescent probes for measurement of mitochondrial membrane potential and also Pgp function. The aim of this study was to investigate whether 2'[(18)F]-fluoroethylrhodamine B ((18)FRB) a halogenated rhodamine derivative previously synthesized for PET assessment of myocardial perfusion preserved its Pgp substrate character. ATPase assay as well as accumulation experiments carried out using Pgp(+) and Pgp(-) human gynecologic (A2780/A2780(AD) and KB-3-1/KB-V1) and a mouse fibroblast cell pairs (NIH 3T3 and NIH 3T3 MDR1) were applied to study the interaction of (18)FRB with Pgp. ATPase assay proved that (18)FRB is a high affinity substrate of Pgp. Pgp(-) cells accumulated the (18)FRB rapidly in accordance with its lipophilic character. Dissipation of the mitochondrial proton gradient by a proton ionophore CCCP decreased the accumulation of rhodamine 123 (R123) and (18)FRB into Pgp(-) cells. Pgp(+) cells exhibited very low R123 and (18)FRB accumulation (around 1-8% of the Pgp(-) cell lines) which was not sensitive to the mitochondrial proton gradient; rather it was increased by the Pgp inhibitor cyclosporine A (CsA). Based on the above data we conclude that (18)FRB is a high affinity Pgp substrate and consequently a potential PET tracer to detect multidrug resistant tumors as well as the function of physiological barriers expressing Pgp.

  8. Radiosynthesis and preliminary biological evaluation of N-(2-[18F]fluoropropionyl)-L-glutamine as a PET tracer for tumor imaging

    PubMed Central

    Tang, Caihua; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Yao, Baoguo; Nie, Dahong

    2016-01-01

    In this study, radiosynthesis and biological evaluation of a new [18F]labeled glutamine analogue, N-(2-[18F]fluoropropionyl)-L-glutamine ([18F]FPGLN) for tumor PET imaging are performed. [18F]FPGLN was synthesized via a two-step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP) with a decay-corrected yield of 30 ± 5% (n=10) and a specific activity of 48 ± 10 GBq/μmol after 125 ± 5 min of radiosynthesis. The biodistribution of [18F]FPGLN was determined in normal Kunming mice and high uptake of [18F]FPGLN was observed within the kidneys and quickly excreted through the urinary bladder. In vitro cell experiments showed that [18F]FPGLN was primarily transported by Na+-dependent system XAG− and was not incorporated into proteins. [18F]FPGLN displayed better stability in vitro than that in vivo. PET/CT studies revealed that intense accumulation of [18F]FPGLN were shown in human SPC-A-1 lung adenocarcinoma and PC-3 prostate cancer xenografts. The results support that [18F]FPGLN seems to be a possible PET tracer for tumor imaging. PMID:27153544

  9. Specific binding of 3N-(2'-[18F]fluoroethyl)benperidol to primate cerebral dopaminergic D2 receptors demonstrated in vivo by PET.

    PubMed

    Moerlein, S M; Perlmutter, J S

    1992-12-14

    3N-(2'-[18F]Fluoroethyl)benperidol ([18F]FEB) an 18F-labeled analogue of the D2 antagonist benperidol, was evaluated as a tracer for positron emission tomography (PET). PET imaging of a living baboon showed that the fluorinated ligand rapidly localized in vivo within D2 receptor-rich brain tissue, with selective retention lasting over 2 h after tracer injection. Pretreatment of the animal with unlabeled D2-specific antagonist eticlopride (4 mg/kg, i.v.) 1 h before [18F]FEB completely abolished the selective disposition of the radioligand, whereas the regional cerebral blood flow, blood volume and peripheral metabolism/protein binding of [18F]FEB were not changed. Tracer localization when the baboon was pretreated with unlabeled ketanserin (0.55 mg/kg, i.v.) or SCH 23390 (1.1 mg/kg, i.v.) was identical to that for the control case, indicating that the [18F]FEB did not bind to S2 of D1 receptors in vivo. [18F]FEB has advantages compared to previously used PET tracers, and may be an excellent radioligand for non-invasive study of D2 receptor binding.

  10. Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy Before Surgery

    PubMed Central

    Giorgetti, Assuero; Pallabazzer, Giovanni; Ripoli, Andrea; Solito, Biagio; Genovesi, Dario; Lencioni, Monica; Fabrini, Maria Grazia; D’Imporzano, Simone; Pieraccini, Laura; Marzullo, Paolo; Santi, Stefano

    2016-01-01

    Abstract To investigate the prognostic value of tumor metabolism measurements on serial 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography scans in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiotherapy. Forty-five patients (63 ± 7 years, 6 female) treated with concomitant chemoradiotherapy before surgery were followed up for 24 ± 18 months (range 4–71). Positron emission tomography and computed tomography scans were obtained within 1 week before the start (PET1) and 1 month after the completion of the treatment (PET2). Total body tumor metabolic activity was measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass, and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters between PET1 and PET2 were calculated and expressed as percentage of PET1 results. At the time of the analysis, 27 patients were dead and 18 were alive. There was no difference between the 2 groups in terms of age, sex, site of the disease, histology, and the presence/absence of linfonodal metastases (P = NS). Survival random forest analysis (20,000 trees) resulted in an estimate of error rate of 36%. The nonparametric approach identified ΔTLG40 as the most predictive factor of survival (relative importance 100%). Moreover, T (17%), N (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the end of chemioradioterapy, and ΔTLG50–70 (17%–5%) were positively associated with patient outcome. The nonparametric analysis confirmed the prognostic importance of some clinical parameters, such as TNM stage and cancer histology. Moreover, ΔTLG resulted to be the most important factor in predicting outcome and should be considered in risk stratification of patients treated with neoadjuvant chemoradiotherapy. PMID:27043676

  11. Is 2-deoxy-2-[18F]fluoro-D-glucose PET/CT acquisition from the upper thigh to the vertex of skull useful in oncological patients?

    PubMed Central

    Salvatore, B.; Caprio, M.G.; Fonti, R.; D’Amico, D.; Fraioli, F.; Salvatore, M.; Pace, L.

    2015-01-01

    Aim To assess whether performing routinely 2-deoxy-2-[18F]fluoro-D-glucose PET/CT (18FDG PET/CT) scan from the upper thigh to the vertex of skull is clinically relevant. Materials and Methods: 3502 (1634 female; mean-age 60+16) consecutive patients undergoing 18FDG PET/CT were retrospectively analyzed. Patients were divided in 10 groups according to primary malignancy. Chi-square analysis was used to assess differences among proportions. A p value < 0.05 was considered significant. Results: 18FDG PET/CT was positive in head district in 130/3502 (3,7%) patients. In all patients lesions were unknown before PET/CT examination. PET/CT showed 158 positive brain/head uptake in the 130 patients. The 158 lesions were localized in: brain (43/158; 27%), bone (52/158; 33%), lymph node (1/158; 0,6%), soft tissue (55/158; 35%) and other sites (7/158; 4,4%). According to each group, patients were positive in the head district in 1.0% for Gastrointestinal Cancer (7/690), 3.0 % for Genitourinary Cancer (3/101), 3.7 % for Haemathologic Cancer (59/1590), 2.7 % for Gynaecologic Cancer (3/112), 7.8% for Head-Neck-Thyroid and Parathyroid Cancer (26/331), 3.5% for Breast Cancer (7/200), 2.6% for Lung Cancer (7/271), 3.4% for Melanoma (2/59), 7.4% for Sarcoma (2/27), 11.6% for Unknown Primary Tumour (14/121). Conclusion: Our data show a relatively high incidence of brain/head lesion in patients with Unknown Primary Tumour. PMID:25674547

  12. Positron Emission Tomography With 2-[18F]-Fluoro-2-Deoxy-D-Glucose For Initial Staging Of Hodgkin Lymphoma: A Single Center Experience In Brazil

    PubMed Central

    Cerci, Juliano Julio; Pracchia, Luís Fernando; Junior, José Soares; da Cruz Gouveia Linardi, Camila; Meneghetti, José Claudio; Buccheri, Valeria

    2009-01-01

    BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET) is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL) in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS) methods, including computed tomography (CT) and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively). FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively). FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82) of the patients and downstaged 11% (9/82) of the patients. As a result of these changes in staging, 15% (13/82) of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients) brought about by the addition of PET to the staging algorithm, even in a

  13. In Vivo Imaging with an αvβ6 Specific Peptide Radiolabeled using 18F-“Click” Chemistry: Evaluation and Comparison with the Corresponding 4-[18F]Fluorobenzoyl- and 2-[18F]Fluoropropionyl-Peptides

    PubMed Central

    Hausner, Sven H.; Marik, Jan; Gagnon, M. Karen J.; Sutcliffe, Julie L.

    2009-01-01

    Numerous radiolabeled peptides have been utilized for in vivo imaging of a variety of cell-surface receptors. For applications in PET using [18F]fluorine, peptides are radiolabeled via a prosthetic group approach. We previously developed solution-phase 18F-“click” radiolabeling and solid-phase radiolabeling using 4-[18F]fluorobenzoic and 2-[18F]fluoropropionic acids. Here we compare the 3 different radiolabeling approaches and report the effects on PET imaging and pharmacokinetics. The prosthetic groups did have an influence; metabolites with significantly different polarities were observed. PMID:18785727

  14. All That Glitters Is Not Gold" - A Case of an Occult Foreign Body in the Lung with Elevated 2-[18F]-Fluoro-2-deoxy-D-glucose (FDG) Uptake Mimicking Bronchogenic Carcinoma

    PubMed Central

    Schenone, Aaron; Reichardt, Brian A; Saladi, Swetha; Mehta, Kris; Poddar, Nishant; Stoeckel, David

    2017-01-01

    Combined positron emission tomography/computed tomography (PET/CT) using the glucose analogue 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) has become the standard of care in oncological patients. However, due to the non-specific nature of FDG uptake, there are many physiological variants and benign pathological entities that also demonstrate augmented glucose metabolism, such as inflammatory and infective processes. Undiagnosed and retained foreign bodies (occult foreign bodies) in the lung can induce inflammatory reaction consisting of polymorphonuclear neutrophils, macrophages, and granulation tissue resulting in intense FDG uptake because of high metabolic activity and cell turnover. Here, we present a case of an occult foreign body imitating a tumor on PET/CT.  PMID:28265526

  15. Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide.

    PubMed

    Morris, Olivia; Gregory, J; Kadirvel, M; Henderson, Fiona; Blykers, A; McMahon, Adam; Taylor, Mark; Allsop, David; Allan, Stuart; Grigg, J; Boutin, Herve; Prenant, Christian

    2016-10-01

    2-[(18)F]-Fluoro-3-pyridinecarboxaldehyde ([(18)F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the product of the reaction with FPCA has been fully characterised. In-vivo biodistribution of [(18)F]RI-OR2-TAT has been measured in Wistar rats.

  16. Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.

    PubMed

    Lemaire, C; Libert, L; Franci, X; Genon, J-L; Kuci, S; Giacomelli, F; Luxen, A

    2015-06-15

    An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment.

  17. The comparison of 2-18F-2-deoxyglucose and 15-(ortho-123I-phenyl)-pentadecanoic acid uptake in persisting defects on thallium-201 tomography in myocardial infarction

    SciTech Connect

    Henrich, M.M.; Vester, E.; von der Lohe, E.; Herzog, H.; Simon, H.; Kuikka, J.T.; Feinendegen, L.E. )

    1991-07-01

    The myocardial uptake of glucose and fatty acids into 201Tl redistribution defects were studied in 32 patients with myocardial infarction by tomography using 2-18F-2-deoxyglucose (FDG) and 15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA). A total of 1153 segments were analyzed, 408 (35%) of which showed a persistent thallium-defect in stress-redistribution images. Of the segments with a decreased 201Tl uptake in these redistribution tomograms, 50.5% had a decreased uptake of both FDG and oPPA; in 21.8% FDG as well as oPPA uptake was within normal range. Normal FDG uptake but decreased oPPA uptake was detected in 17.4%, whereas 10.3% of the segments had normal oPPA uptake but decreased FDG uptake (chi-square test, p less than 0.001). A significant correlation of FDG and oPPA uptake (r = 0.51) was found in the segments with persistent 201Tl defect. Thus, a substantial fraction of persistent thallium-defects after healed myocardial infarction exhibit FDG as well as oPPA uptake, probably due to residual fatty acid metabolism in partially ischemic regions.

  18. Automated synthesis of N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid as an amino acid tracer for tumor imaging on a modified [(18) F]FDG synthesis module.

    PubMed

    Liu, Shaoyu; Sun, Aixia; Zhang, Zhanwen; Tang, Xiaolan; Nie, Dahong; Ma, Hui; Jiang, Shende; Tang, Ganghua

    2017-04-03

    N-(2-[(18) F]Fluoropropionyl)-L-glutamic acid ([(18) F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography (PET). However, due to the complicated multi-step synthesis, the routine production of [(18) F]FPGLU presents many challenging laboratory requirements. In order to simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [(18) F]FPGLU was performed on a modified commercial FDG synthesizer via a two-step on-column hydrolysis procedure, including (18) F-fluorination and on-column hydrolysis reaction. [(18) F]FPGLU was synthesized in 12 ± 2% (n = 10, uncorrected) radiochemical yield based on [(18) F]fluoride using the tosylated precursor 2. The radiochemical purity was ≥98%, and the overall synthesis time was 35 min. To further optimize the radiosynthesis conditions of [(18) F]FPGLU, a brominated precursor 3 was also used for the preparation of [(18) F]FPGLU and the improved radiochemical yield was up to 20 ± 3% (n = 10, uncorrected) in 35 min. Moreover, all these results were achieved using the similar on-column hydrolysis procedure on the modified FDG synthesis module.

  19. Synthesis and evaluation of 2-18F-fluoro-5-iodo-3-[2-(S)-3,4-dehydropyrrolinylmethoxy]pyridine (18F-Niofene) as a potential imaging agent for nicotinic α4β2 receptors

    PubMed Central

    Kuruvilla, Sharon A; Hillmer, Ansel T; Wooten, Dustin W; Patel, Ashna; Christian, Bradley T; Mukherjee, Jogeshwar

    2014-01-01

    Nicotinic α4β2 acetylcholine receptors (nAChRs) have been implicated in various pathophysiologies including neurodegenerative diseases. Currently, 2-18F-A85380 (2-FA) and 5-123I-A85380 (5-IA) are used separately in human PET and SPECT studies respectively and require >4-6 hours of scanning. We have developed 2-fluoro-5-iodo-3-[2-(S)-3-dehydropyrrolinylmethoxy]pyridine (niofene) as a potential PET/SPECT imaging agent for nAChRs with an aim to have rapid binding kinetics similar to that of 18F-nifene used in PET studies. Niofene exhibited a 10-fold better in vitro binding affinity in rat brain than that of nicotine. The relative binding of niofene was similar to that of niodene and twice as better as that of nifene. In vitro autoradiography in rat brain slices alongside niodene indicated selective binding of niofene to regions consistent with α4β2 receptor distribution. Niofene, 10 nM, displaced >70% of 3H-cytisine bound to α4β2 receptors in rat brain slices. Radiolabeling of 18F-niofene was achieved in 10-15% radiochemical yield in high specific activities >2 Ci/μmol and showed rapid in vivo kinetics similar to that of 18F-nifene and 18F-nifrolene. In vivo PET in rats showed rapid uptake in the brain and selective localization in receptor regions such as the thalamus (TH). Pseudoequilibrium with 18F-niofene was achieved in 30-40 minutes, which is similar to that of 18F-nifene. Further evaluation of 18F-niofene as a potential PET imaging agent is underway. Future studies will be conducted to radiolabel niofene with iodine-123 for use in SPECT imaging. PMID:24982821

  20. Determination of hepatic galactose elimination capacity using 2-[18F]fluoro-2-deoxy-D-galactose PET/CT: reproducibility of the method and metabolic heterogeneity in a normal pig liver model

    PubMed Central

    SØRENSEN, MICHAEL

    2011-01-01

    Objective A PET method is developed for non-invasive measurement of regional metabolic liver function using the galactose analog 2-[18F]fluoro-2-deoxy-D-galactose, FDGal. The aim of the present study was to determine the reproducibility of the method in pigs before translating it to human studies. Material and methods Five anesthetized pigs were studied twice within an interval of three days. A dynamic PET recording was performed with an injection of 100 MBq FDGal. Non-radioactive galactose was administered throughout the PET recordings to achieve near-saturated elimination kinetics. Arterial blood samples were collected for determination of blood concentrations of FDGal and galactose (cgal). Net metabolic clearance of FDGal, KFDGal, was calculated from linear representation of data. The approximate maximal hepatic removal rate, Vmax, of galactose (mmol/l tissue/min) was calculated as KFDGal cgal. The estimates from Day 1 and Day 2 were compared and the coefficient of variation, COV, of the estimates calculated. Functional heterogeneity in normal pig liver was evaluated as COV of the tissue concentration of radioactivity during quasi steady-state metabolism. Results There was no significant difference between Vmax from Day 1 and Day 2 (p = 0.38), and the reproducibility was good with a COV of 14% for the whole liver. In normal pig liver tissue, mean COV after an injection of FDGal was on average 15.6% with no day-to-day variation (p = 0.7). Conclusions The novel FDGal PET method for determination of hepatic metabolic function has a good reproducibility and is promising for future human studies of regional liver function. PMID:20695723

  1. Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography in differential diagnosis of benign and malignant intraductal papillary-mucinous neoplasm of the pancreas.

    PubMed

    Tomimaru, Yoshito; Takeda, Yutaka; Tatsumi, Mitsuaki; Kim, Tonsok; Kobayashi, Shogo; Marubashi, Shigeru; Eguchi, Hidetoshi; Tanemura, Masahiro; Kitagawa, Toru; Nagano, Hiroaki; Umeshita, Koji; Wakasa, Kenichi; Doki, Yuichiro; Mori, Masaki

    2010-09-01

    Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas presents in various histopathological stages from benign to malignant lesions. The differentiation between benign and malignant IPMN is important in order to determine the treatment of the patients. However, pre-operative differentiation remains difficult. The aim of this study was to assess the utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in pre-operative differentiation of benign and malignant IPMN of the pancreas. In the present study we prospectively investigated 29 patients who underwent CT, FDG-PET, and surgery for IPMNs, followed by histopathological examination. The maximum standardized uptake value (SUVmax) was determined on FDG-PET, and differentiation of benign from malignant IPMN was tested using various SUVmax cut-off levels and various parameters derived from the CT. SUVmax was found to be significantly higher in malignant IPMNs (4.7+/-3.0) than that in benign IPMNs (1.8+/-0.3, P=0.0011). SUVmax values correlated with the histopathological types of IPMN (adenoma/borderline lesion/carcinoma in situ/invasive carcinoma) (Spearman rank correlation 0.865, P<0.0001). The specificity, sensitivity and accuracy values were best for SUVmax of 2.5 (100, 93, and 96%, respectively). The combination of mural nodule, detected on CT, and SUVmax of 2.5 offered the best diagnosis of malignant IPMN. These results suggest that FDG-PET is useful for differentiation of malignant IPMN of the pancreas, and that it should be performed in combination with other conventional imaging modalities.

  2. Comparison between 2-(18) F-fluoro-2-deoxy-d-glucose positron emission tomography and contrast-enhanced computed tomography for measuring gross tumor volume in cats with oral squamous cell carcinoma.

    PubMed

    Yoshikawa, Hiroto; Randall, Elissa K; Kraft, Susan L; Larue, Susan M

    2013-01-01

    Feline oral squamous cell carcinoma is one of the most refractory feline malignancies. Most patients succumb due to failure in local tumor control. 2-(18) F-fluoro-2-deoxy-D-glucose positron emission tomography ((18) F-FDG PET) is increasingly being used for veterinary oncology staging as it highlights areas with higher glucose metabolism. The goal of the current prospective study was to compare gross tumor volume measurements using (18) F-FDG PET vs. those using computed tomography (CT) for stereotactic radiation therapy planning in cats with oral squamous cell carcinoma. Twelve cats with confirmed oral squamous cell carcinoma underwent pretreatment (18) F-FDG PET/CT. Gross tumor volumes based on contrast-enhanced CT and (18) F-FDG PET were measured and compared among cats. Mean PET gross tumor volume was significantly smaller than mean CT gross tumor volume in the mandibular/maxillary squamous cell carcinoma group (n = 8, P = 0.002) and for the total number of patients (n = 12, P = 0.006), but not in the lingual/laryngeal group (n = 4, P = 0.57). Mismatch fraction analysis revealed that most of the lingual/laryngeal patients had a large region of high-(18) F-FDG activity outside of the CT gross tumor volume. This mismatch fraction was significantly greater in the lingual/laryngeal group than the mandibular/maxillary group (P = 0.028). The effect of poor spatial resolution of PET imaging was greater when the absolute tumor volume was small. Findings from this study indicated that (18) F-FDG PET warrants further investigation as a supplemental imaging modality in cats with oral squamous cell carcinoma because it detected regions of possible primary tumor that were not detected on CT images.

  3. Comparison of Positron Emission Tomography Using 2-[18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[18F]-fluorothymidine in Lung Cancer Imaging

    PubMed Central

    Wang, Fu-Li; Tan, Ye-Ying; Gu, Xiang-Min; Li, Tian-Ran; Lu, Guang-Ming; Liu, Gang; Huo, Tian-Long

    2016-01-01

    Background: The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging. Methods: The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated. Results: The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P < 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P < 0.05 and r = 0.724, P < 0.01, respectively). Conclusions: The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor

  4. Ferret thoracic anatomy by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (18F-FDG PET/CT) imaging.

    PubMed

    Wu, Albert; Zheng, Huaiyu; Kraenzle, Jennifer; Biller, Ashley; Vanover, Carol D; Proctor, Mary; Sherwood, Leslie; Steffen, Marlene; Ng, Chin; Mollura, Daniel J; Jonsson, Colleen B

    2012-01-01

    The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with (18)F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of (18)F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUV(Max)] 8.60, mean standardized uptake value [SUV(Mean)] 5.42), thymus (SUV(Max) 3.86, SUV(Mean) 2.59), liver (SUV(Max) 1.37, SUV(Mean) 0.99), right lung (SUV(Max) 0.92, SUV(Mean) 0.56), and left lung (SUV(Max) 0.88, SUV(Mean) 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of (18)F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that (18)F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They

  5. Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging

    PubMed Central

    Wu, Albert; Zheng, Huaiyu; Kraenzle, Jennifer; Biller, Ashley; Vanover, Carol D.; Proctor, Mary; Sherwood, Leslie; Steffen, Marlene; Ng, Chin; Mollura, Daniel J.; Jonsson, Colleen B.

    2013-01-01

    The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with 18F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of 18F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUVMax] 8.60, mean standardized uptake value [SUVMean] 5.42), thymus (SUVMax 3.86, SUVMean 2.59), liver (SUVMax 1.37, SUVMean 0.99), right lung (SUVMax 0.92, SUVMean 0.56), and left lung (SUVMax 0.88, SUVMean 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of 18F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that 18F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging

  6. Synthesis of 2'-deoxy-2'-[18F]fluoro-beta-D-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Synthesis of [18F]labelled FAU, FMAU, FBAU, FIAU.

    PubMed

    Mangner, Thomas J; Klecker, Raymond W; Anderson, Lawrence; Shields, Anthony F

    2003-04-01

    An efficient and reliable synthesis of 2'-deoxy-2'-[(18)F]fluoro-beta-D-arabinofuranosyl nucleosides is presented. Overall decay-corrected radiochemical yields of 35-45% of 4 analogs, FAU, FMAU, FBAU and FIAU are routinely obtained in >98% radiochemical purity and with specific activities of greater than 3 Ci/micromol (110 MBq/micromol) in a synthesis time of approximately 3 hours. When approximately 220 mCi (8.15 GBq) of starting [(18)F]fluoride is used, 25 -30 mCi (0.93 -1.11 GBq) of product (enough to image two patients sequentially) is typically obtained.

  7. Simple and efficient synthesis of 2-[(18)F]fluoroethyl triflate for high yield (18)fluoroethylation.

    PubMed

    Peters, Tanja; Vogg, Andreas; Oppel, Iris M; Schmaljohann, Jörn

    2014-12-01

    The [(18)F]fluoroethyl moiety has been widely utilized in the synthesis of (18)F-labelled compounds. The aim of this work was the reliable synthesis of [(18)F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [(18)F]FEB and [(18)F]FEtOTos. [(18)F]FEtOTf and the intermediate [(18)F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE. The high potency of [(18)F]FEtOTf was shown by the efficient alkylation of the deactivated nucleophile aniline under mild conditions, as well as by the synthesis of [(18)F]FEC.

  8. History of the first synthesis of 2-deoxy-2-fluoro-D-glucose the unlabeled forerunner of 2-deoxy-2-[18F]fluoro-D-glucose.

    PubMed

    Pacák, Josef; Cerný, Miloslav

    2002-10-01

    The history of the first successful synthesis of 2-deoxy-2-fluoro-D-glucose (19FDG) is described. In many aspects, this substance imitates the behavior of naturally occurring glucose. For example, it is transported into the cells and is converted to the corresponding 6-phosphate by the enzyme hexokinase in a manner similar to glucose. Due to the presence of the fluorine atom at C-2, however, this phosphate derivative does not undergo further glycolysis but is metabolically trapped in the cell. Thanks to these properties, eight years after the synthesis of 19FDG, its 18F-labeled derivative was successfully used with positron emission tomography (PET).

  9. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography

    PubMed Central

    Esmail, H; Lai, RP; Lesosky, M; Wilkinson, KA; Graham, CM; Coussens, AK; Oni, T; Warwick, JM; Said-Hartley, Q; Koegelenberg, CF; Walzl, G; Flynn, JL; Young, DB; Barry, CE; O’Garra, A; Wilkinson, RJ

    2016-01-01

    Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral therapy naïve, HIV-1 infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were significantly more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers predictive of progression. PMID:27595321

  10. (R,S)-anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid: synthesis from racemic 2-benzyloxycyclopentanone and biological evaluation for brain tumor imaging with positron emission tomography.

    PubMed

    Jarkas, Nachwa; Voll, Ronald J; Williams, Larry; Camp, Vernon M; Goodman, Mark M

    2010-09-23

    (R,S)-anti-1-amino-2-fluorocyclopentyl-1-carboxylic acid (2-FACPC, 4b) was radiolabeled in 39% yield starting from cyclic sulfamidate 12. The 9L gliosarcoma cells assays showed that 4b is mainly a substrate for the L-type amino acid transport with some affinity to the A-type. In rats bearing 9L gliosarcoma tumors, 4b displayed high tumor to brain ratio (10:1) at 120 min after injection. FACPC is an attractive candidate for imaging brain tumors with PET, and its isolated enantiomers are under investigation.

  11. Combined O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) Positron Emission Tomography (PET) and Simultaneous Magnetic Resonance Imaging (MRI) Follow-up in Re-irradiated Recurrent Glioblastoma Patients

    ClinicalTrials.gov

    2012-12-17

    Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

  12. Direct radiolabelling of proteins at cysteine using [18F]-fluorosugars.

    PubMed

    Boutureira, Omar; Bernardes, Gonçalo J L; D'Hooge, François; Davis, Benjamin G

    2011-09-28

    A strategy for the site-specific attachment of 2-deoxy-2-fluorosugars to cysteine and dehydroalanine tagged proteins is reported. When combined with thionation of fluorosugars, such as the widely available (18)F probe 2-deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG), this methodology allows fast and direct access to site-specific [(18)F]FDG-labelled proteins.

  13. A Laser Feedback Control Design for Passive Ring Laser Gyros in a Very High Finesse Cavity.

    DTIC Science & Technology

    1985-12-01

    14 II. Theory ....................... 16 Optical Cavities ................ 16 Laser Fundamentals ...............24 The Gaussian Beam. ...............28...c 1-(ABC 1h(.8 = (2.18) F = 1 2.19) - (RARCRD) t = = (2.20) C c[i- (RARRc%)] Laser Fundamentals A laser consists of three basic components: a gain

  14. Epileptic Activity Increases Cerebral Amino Acid Transport Assessed by 18F-Fluoroethyl-l-Tyrosine Amino Acid PET: A Potential Brain Tumor Mimic.

    PubMed

    Hutterer, Markus; Ebner, Yvonne; Riemenschneider, Markus J; Willuweit, Antje; McCoy, Mark; Egger, Barbara; Schröder, Michael; Wendl, Christina; Hellwig, Dirk; Grosse, Jirka; Menhart, Karin; Proescholdt, Martin; Fritsch, Brita; Urbach, Horst; Stockhammer, Guenther; Roelcke, Ulrich; Galldiks, Norbert; Meyer, Philipp T; Langen, Karl-Josef; Hau, Peter; Trinka, Eugen

    2017-01-01

    O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect (18)F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by (18)F-FET PET and to elucidate the pathophysiologic background.

  15. Condyloma acuminata induces focal intense FDG uptake mimicking vaginal stump recurrence from uterine cervical cancer: a case report.

    PubMed

    Kishimoto, T; Mabuchi, S; Kato, H; Kimura, T

    2013-01-01

    The 2-deoxy-2-[18F] fluoro-D-glucose position emission tomography/computed tomography (FDG PET/CT) findings of condyloma acuminata in a patient with FIGO Stage IB1 cervical cancer who had previously been treated with radical hysterectomy, pelvic chemoradiotherapy, and consolidation chemotherapy is described in this article. This case highlights the importance of considering condyloma acuminata during the differential diagnosis of abnormal vaginal FDG uptake in patients who have been treated for gynecological cancer.

  16. N-Succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([18F]SFBTMGMB): A Residualizing Label for 18F-labeling of internalizing biomolecules

    PubMed Central

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Pruszynski, Marek; Koumarianou, Eftychia; Zhou, Zhengyuan; Zalutsky, Michael R.

    2015-01-01

    Residualizing labeling methods for internalizing peptides and proteins are designed to trap the radionuclide inside the cell after intracellular degradation of the biomolecule. The goal of this work was to develop a residualizing label for the 18F-labeling of internalizing biomolecules based on a template used successfully for radioiodination. N-succinimidyl 3-((4-(4-[18F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(bis-Boc-guanidinomethyl)benzoate (Boc2-[18F]SFBTMGMB) was synthesized by click reaction of an azide precursor and [18F]fluorohexyne in 8.5 ± 2.8% average decay-corrected radiochemical yield (n =15). An anti-HER2 nanobody 5F7 was labeled with 18F using [18F]SFBTMGMB ([18F]RL-I), obtained by the deprotection of Boc2-[18F]SFBTMGMB, in 31.2 ± 6.7% (n =5) conjugation efficiency. Thus labeled nanobody had a radiochemical purity of >95%, bound to the HER2-expressing BT474M1 breast cancer cells with an affinity of 4.7 ± 0.9 nM, and had an immunoreactive fraction of 62–80%. In summary, a novel residualizing prosthetic agent for labeling biomolecules with 18F has been developed. An anti-HER2 nanobody was labeled using this prosthetic group with retention of affinity and immunoreactivity to HER2. PMID:26645790

  17. Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.

    PubMed

    Lee, Chung-Cheng; Sui, Guodong; Elizarov, Arkadij; Shu, Chengyi Jenny; Shin, Young-Shik; Dooley, Alek N; Huang, Jiang; Daridon, Antoine; Wyatt, Paul; Stout, David; Kolb, Hartmuth C; Witte, Owen N; Satyamurthy, Nagichettiar; Heath, James R; Phelps, Michael E; Quake, Stephen R; Tseng, Hsian-Rong

    2005-12-16

    Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.

  18. Automated production of [18F]VAT suitable for clinical PET study of vesicular acetylcholine transporter

    PubMed Central

    Yue, Xuyi; Bognar, Christopher; Zhang, Xiang; Gaehle, Gregory; Moerlein, Stephen M.; Perlmutter, Joel S.; Tu, Zhude

    2015-01-01

    Automated production of a promising radiopharmaceutical (-)-(1-(8-(2-[18F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([18F]VAT) for vesicular acetylcholine transporter(VAChT) was achieved using a two-step procedure in a current good manufacturing practices fashion. The production of [18F]VAT was accomplished in approximately 140 min, with radiochemical yield of ~15.0% (decay corrected), specific activity > 111 GBq/μmol, radiochemical purity > 99% and mass of VAT ~3.4 μg/batch (n > 10). The radiopharmaceutical product meets all quality control criteria for human use, and is suitable for clinical PET studies of VAChT. PMID:26408913

  19. Individual refinement of attenuation correction maps for hybrid PET/MR based on multi-resolution regional learning.

    PubMed

    Shi, Kuangyu; Fürst, Sebastian; Sun, Liang; Lukas, Mathias; Navab, Nassir; Förster, Stefan; Ziegler, Sibylle I

    2016-11-19

    PET/MR is an emerging hybrid imaging modality. However, attenuation correction (AC) remains challenging for hybrid PET/MR in generating accurate PET images. Segmentation-based methods on special MR sequences are most widely recommended by vendors. However, their accuracy is usually not high. Individual refinement of available certified attenuation maps may be helpful for further clinical applications. In this study, we proposed a multi-resolution regional learning (MRRL) scheme to utilize the internal consistency of the patient data. The anatomical and AC MR sequences of the same subject were employed to guide the refinement of the provided AC maps. The developed algorithm was tested on 9 patients scanned consecutively with PET/MR and PET/CT (7 [(18)F]FDG and 2 [(18)F]FET). The preliminary results showed that MRRL can improve the accuracy of segmented attenuation maps and consequently the accuracy of PET reconstructions.

  20. Imaging Enterobacteriaceae infection in vivo with 18F-fluorodeoxysorbitol positron emission tomography

    PubMed Central

    Weinstein, Edward A.; Ordonez, Alvaro A.; DeMarco, Vincent P.; Murawski, Allison M.; Pokkali, Supriya; MacDonald, Elizabeth M.; Klunk, Mariah; Mease, Ronnie C.; Pomper, Martin G.; Jain, Sanjay K.

    2015-01-01

    The Enterobacteriaceae are a family of rod-shaped Gram-negative bacteria that normally inhabit the gastrointestinal tract and are the most common cause of Gram-negative bacterial infections in humans. In addition to causing serious multidrug-resistant, hospital-acquired infections, a number of Enterobacteriaceae species are also recognized as biothreat pathogens. As a consequence, new tools are urgently needed to specifically identify and localize infections due to Enterobacteriaceae and to monitor antimicrobial efficacy. In this report, we used commercially available 2-[18F]-fluorodeoxyglucose (18F-FDG) to produce 2-[18F]-fluorodeoxysorbitol (18F-FDS), a radioactive probe for Enterobacteriaceae, in 30 min. 18F-FDS selectively accumulated in Enterobacteriaceae, but not in Gram-positive bacteria or healthy mammalian or cancer cells in vitro. In a murine myositis model, 18F-FDS positron emission tomography (PET) rapidly differentiated true infection from sterile inflammation with a limit of detection of 6.2 ± 0.2 log10 colony-forming units (CFU) for Escherichia coli. Our findings were extended to models of mixed Gram-positive and Gram-negative thigh co-infections, brain infection, Klebsiella pneumonia, and mice undergoing immunosuppressive chemotherapy. This technique rapidly and specifically localized infections due to Enterobacteriaceae, providing a three-dimensional holistic view within the animal. Last, 18F-FDS PET monitored the efficacy of antimicrobial treatment, demonstrating a PET signal proportionate to the bacterial burden. Therapeutic failures associated with multidrug-resistant, extended-spectrum β-lactamase (ESBL)–producing E. coli infections were detected in real time. Together, these data show that 18F-FDS is a candidate imaging probe for translation to human clinical cases of known or suspected infections owing to Enterobacteriaceae. PMID:25338757

  1. 18F-AFETP, 18F-FET, and 18F-FDG Imaging of Mouse DBT Gliomas

    PubMed Central

    Sai, Kiran Kumar Solingapuram; Huang, Chaofeng; Yuan, Liya; Zhou, Dong; Piwnica-Worms, David; Garbow, Joel R.; Engelbach, John A.; Mach, Robert H.; Rich, Keith M.; McConathy, Jonathan

    2013-01-01

    The goal of this study was to evaluate the 18F-labeled nonnatural amino acid (S)-2-amino-3-[1-(2-18F-fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (18F-AFETP) as a PET imaging agent for brain tumors and to compare its effectiveness with the more-established tracers O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and 18F-FDG in a murine model of glioblastoma. The tracer 18F-AFETP is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport, a relatively unexplored target for oncologic imaging. Methods 18F-AFETP was prepared using the click reaction. BALB/c mice with intracranially implanted delayed brain tumor (DBT) gliomas (n = 4) underwent biodistribution and dynamic small-animal PET imaging for 60 min after intravenous injection of 18F-AFETP. Tumor and brain uptake of 18F-AFETP were compared with those of 18F-FDG and 18F-FET through small-animal PET analyses. Results 18F-AFETP demonstrated focally increased uptake in tumors with good visualization. Peak tumor uptake occurred within 10 min of injection, with stable or gradual decrease over time. All 3 tracers demonstrated relatively high uptake in the DBTs throughout the study. At late time points (47.5–57.5 min after injection), the average standardized uptake value with 18F-FDG (1.9 ± 0.1) was significantly greater than with 18F-FET (1.1 ± 0.1) and 18F-AFETP (0.7 ± 0.2). The uptake also differed substantially in normal brain, with significant differences in the standardized uptake values at late times among 18F-FDG (1.5 ± 0.2), 18F-FET (0.5 ± 0.05), and 18F-AFETP (0.1 ± 0.04). The resulting average tumor-to-brain ratio at the late time points was significantly higher for 18F-AFETP (7.5 ± 0.1) than for 18F-FDG (1.3 ± 0.1) and 18F-FET (2.0 ± 0.3). Conclusion 18F-AFETP is a promising brain tumor imaging agent, providing rapid and persistent tumor visualization, with good tumor–to–normal-brain ratios in the DBT glioma model. High tumor-to-brain, tumor

  2. ELIXYS - a fully automated, three-reactor high-pressure radiosynthesizer for development and routine production of diverse PET tracers

    PubMed Central

    2013-01-01

    Background Automated radiosynthesizers are vital for routine production of positron-emission tomography tracers to minimize radiation exposure to operators and to ensure reproducible synthesis yields. The recent trend in the synthesizer industry towards the use of disposable kits aims to simplify setup and operation for the user, but often introduces several limitations related to temperature and chemical compatibility, thus requiring reoptimization of protocols developed on non-cassette-based systems. Radiochemists would benefit from a single hybrid system that provides tremendous flexibility for development and optimization of reaction conditions while also providing a pathway to simple, cassette-based production of diverse tracers. Methods We have designed, built, and tested an automated three-reactor radiosynthesizer (ELIXYS) to provide a flexible radiosynthesis platform suitable for both tracer development and routine production. The synthesizer is capable of performing high-pressure and high-temperature reactions by eliminating permanent tubing and valve connections to the reaction vessel. Each of the three movable reactors can seal against different locations on disposable cassettes to carry out different functions such as sealed reactions, evaporations, and reagent addition. A reagent and gas handling robot moves sealed reagent vials from storage locations in the cassette to addition positions and also dynamically provides vacuum and inert gas to ports on the cassette. The software integrates these automated features into chemistry unit operations (e.g., React, Evaporate, Add) to intuitively create synthesis protocols. 2-Deoxy-2-[18F]fluoro-5-methyl-β-l-arabinofuranosyluracil (l-[18F]FMAU) and 2-deoxy-2-[18F]fluoro-β-d-arabinofuranosylcytosine (d-[18F]FAC) were synthesized to validate the system. Results l-[18F]FMAU and d-[18F]FAC were successfully synthesized in 165 and 170 min, respectively, with decay-corrected radiochemical yields of 46% ± 1% (n = 6

  3. Voxel-based analysis of Alzheimer's disease PET imaging using a triplet of radiotracers: PIB, FDDNP, and FDG.

    PubMed

    Shin, Jonghan; Lee, Sang-Yoon; Kim, Seog Ju; Kim, So-Hee; Cho, Seong-Jin; Kim, Young-Bo

    2010-08-15

    Beta amyloid plaques, neurofibrillary tangles, and impaired glucose metabolism are among the most prevalent pathological characteristics of Alzheimer's disease (AD). However, separate visualization of these three AD-related pathologies in living humans has not been conducted. Here, we show that positron emission tomography (PET) imaging using the three radiotracers (11)C-Pittsburgh compound B (PIB), 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (FDDNP), and 2-[18F]fluoro-2-deoxy-d-glucose (FDG), in the same subjects, with and without AD, can provide valuable information on the pathological patterns of the distribution of tracers for amyloid plaque, neurofibrillary tangle, and glucose hypometabolism in AD. Voxel-based analysis of PIB-PET in patients with AD compared with normal control subjects showed that patients with AD have highly significant PIB retention in brain regions known to have high amyloid plaque deposition (e.g., frontal, parietal, temporal, and posterior cingulate/precuneus cortices). In contrast, voxel-based analysis of FDDNP-PET showed significantly high FDDNP binding in some brain regions known to have high tangle accumulation in patients with AD compared with age-matched normal subjects (e.g., entorhinal cortex, inferior temporal gyrus, and secondary visual cortex). In addition, because FDDNP binds both plaques and tangles but PIB binds plaques specifically, we examined subtracted PET data (FDDNP minus PIB) acquired from the same patients with AD using an SPM analysis. We found that the hippocampal formation was the most significant brain region in the voxel mapping of FDDNP minus PIB in the same patients with AD. Voxel-based analysis of FDG-PET in the same subjects revealed that brain regions with glucose hypometabolism in patients with AD overlap with regions of high PIB binding. In conclusion, PET imaging using these three radiotracers in the same subjects may contribute toward developing and testing disease

  4. [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.

  5. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging.

    PubMed

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan

    2016-08-15

    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  6. PET imaging of primary mediastinal tumours.

    PubMed Central

    Kubota, K.; Yamada, S.; Kondo, T.; Yamada, K.; Fukuda, H.; Fujiwara, T.; Ito, M.; Ido, T.

    1996-01-01

    Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours. Images Figure 1 Figure 2 PMID:8611400

  7. Positron emission tomography of fluorine-18-deoxyglucose and image-guided phosphorus-31 magnetic resonance spectroscopy in brain tumors

    SciTech Connect

    Heiss, W.D.; Heindel, W.; Herholz, K.; Rudolf, J.; Bunke, J.; Jeske, J.; Friedmann, G. )

    1990-03-01

    Positron emission tomography (PET) of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) and volume-selective phosphorus-31 magnetic resonance spectroscopy (31P-MRS) are methods used to assess the energy metabolism of the brain. Both methods were studied with respect to their contribution to differential diagnosis in 23 patients with various brain tumors. The various neuroectodermal tumors differed with respect to their metabolic rate for glucose (MRGL). Benign and malignant tumors could be better differentiated by using tumor metabolism relative to contralateral brain and by evaluating heterogeneities in tumors. Low-grade gliomas usually showed normal 31P-MR spectra; high-grade gliomas were characterized by reduced and often split phosphodiester peaks and alkaline pH. Meningiomas, which had variable MRGL, typically showed extremely low phosphocreatine levels, reduced phosphodiesters, and alkaline pH. We concluded that FDG-PET and 31P-MRS examine different aspects of tumor metabolism. Therefore, both can contribute independently and complementarily to the differential diagnosis of brain tumors.

  8. Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls.

    PubMed

    Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

    2015-01-01

    The whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p < 0.05; unpaired t test). In addition, SUVibm, SUVlbm, as well as SUVbsa in the abdominal aorta were significantly higher in the HD group as compared to those in the NC group (p < 0.05; unpaired t test). In conclusion, as compared to normal subjects, chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool.

  9. 18F-FDG PET/CT in Neurolymphomatosis: Report of 3 Cases

    PubMed Central

    Canh, Nguyen Xuan; Tan, Ngo Van; Tung, Tran Thanh; Son, Nguyen Truong; Maurea, Simone

    2014-01-01

    Neurolymphomatosis is a rare manifestation of non-Hodgkin lymphoma characterized by infiltration of peripheral nerves, nerve roots, plexus and cranial nerves by malignant lymphocytes. This report presents positron emission tomography/computed tomography (PET/CT)imaging with 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) in 3 cases of non-Hodgkin lymphoma with nerve infiltration, including one newly diagnosed lymphoma, one recurrent lymphoma in previous nerve lesions and one newly recurrent lymphoma. PET/CT could reveal the affected neural structures including cranial nerves, spinal nerve roots, brachial plexus, cervicothoracic ganglion, intercostal nerves, branches of the vagus nerve, lumbosacral plexus and sciatic nerves. There was relative concordance between PET/CT and MRI in detection of affected cranial nerves. PET/CT seemed to be better than MRI in detection of affected peripheral nerves. 18F-FDG PET/CT was a whole-body imaging technique with the ability to reveal the affected cranial nerves, peripheral nerves, nerve roots and plexus in non-Hodgkin lymphoma. A thorough understanding of disease and use of advanced imaging modalities will increasingly detect neurolymphomatosis. PMID:27408859

  10. Hodgkin's lymphoma--patient's assessment and staging.

    PubMed

    Gospodarowicz, Mary K

    2009-01-01

    Hodgkin's lymphoma is one of the most curable malignancies today. But treatment is associated with significant toxicity. The objective of high-quality management is to minimize treatment exposure while maximizing cure of disease. Principles of cancer staging and patient's assessment taxonomy are important to improve communication. An orderly patient evaluation and systematic recording of disease extent using the Ann Arbor classification forms the basis for treatment decision, response assessment, and clinical trials. The practice of staging in Hodgkin's lymphoma evolved over the past 40 years from clinical examination and plain imaging to modern anatomic and functional imaging. Although useful in the past, staging laparotomy, lymphangiograms, and Gallium scintigraphy have now been abandoned. Computerized tomography combined with 2-[18F]fluoro-2-deoxyglucose-positron emission tomography form the basis for anatomic disease extent assessment. Although patients' evaluation and staging at diagnosis are important, the management of Hodgkin's lymphoma involves a complex series of algorithms requiring interim and overall response assessment, careful follow-up, repeat assessment, and salvage management of recurrent disease.

  11. Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).

    PubMed

    Bouhlel, Ahlem; Alyami, Wadha; Li, Aixiao; Yuan, Liya; Rich, Keith; McConathy, Jonathan

    2016-04-14

    Two [(18)F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[(18)F]fluoro-2-methylheptanoic acid ((S)-[(18)F]FAMHep, (S)-[(18)F]14) and (S)-2-amino-7-[(18)F]fluoroheptanoic acid ((S)-[(18)F]FAHep, (S)-[(18)F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[(18)F]15 but not (S)-[(18)F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[(18)F]15 in normal brain. (S)-[(18)F]15 had imaging properties similar to those of (S)-[(18)F]FET in the DBT tumor model while (S)-[(18)F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.

  12. Design of an Automated System for Synthesis of [18 F] FDG for PET Investigation at IFIN-HH Bucharest

    NASA Astrophysics Data System (ADS)

    Craciun, Liviu Stefan; Cimpeanu, Catalina; Constantinescu, Olimpiu; Dudu, Dorin; Ionescu, Cristina; Negoita, Nicolae; Racolta, Petru Mihai; Rusen, Ion

    2009-03-01

    A novel apparatus constructed at IFIN-HH is described for automated synthesis of radiopharmaceuticals labeled with 18F for use in positron emission tomography (PET) investigations. [18 F] fluoride was produced at the IFIN-HH cyclotron by irradiation of H2O enriched 97% in 18O with 13 MeV deuterons, or 8 MeV protons. The irradiated H2O was transferred (injected) into the radiochemical fully-automated processing systems which ensured the separation of 18F from H2O, the labeling with 18F, and finally purified by filtration with selective absorbants. The system is easy to operate and contains a programmable logical controller that manages the entire operation program stored in its internal memory. The computer is used to assist the operator during the different steps of synthesis and to allow visualization of the process and printing the report. The device was used for used for the production of 2-[18 F] FLUORO-2-DEOXY-D-GLUCOSE at the IFIN-HH cyclotron, one of the most used radiopharmaceutical in PET investigations. The synthesis module is configured so that is flexible enough to accomplish other nucleophile reactions of labeling with short lived radioisotopes.

  13. Long-lasting in vivo and in vitro antibacterial ability of nanostructured titania coating incorporated with silver nanoparticles.

    PubMed

    Cheng, Hao; Li, Yong; Huo, Kaifu; Gao, Biao; Xiong, Wei

    2014-10-01

    Although titanium (Ti) implants are widely used clinically, implant-associated bacterial infection is still one of the most serious complications in orthopedic surgery. Long-term antibacterial properties and the ability to inhibit biofilm formation are highly desirable to prevent implant associated infection. In this study, a controllable amount of silver (Ag) nanoparticles was incorporated into titanium oxide; or titanium, nanotubes (TiO₂ -NTs). The reliable release and long-term antibacterial function of Ag, in vivo and in vitro, and influence normal bone-implant integration from the Ag released from Ag-incorporated NTs in vivo have been studied to make them useable in clinical practice. In the current study, TiO₂ -NTs loaded with Ag (NT-Ag) exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC43300) in vitro for 30 days, and the ability to penetrate the protein layer well. In addition, X-ray examination and 2-[(18)F]-fiuoro-2-deoxy-D-glucose positron emission tomography indicates that NT-Ag show extremely long antibacterial activity in vivo in a rat model. Furthermore, histomorphometric analysis demonstrated that satisfactory bio-integration can be expected. Our results indicate that NT-Ag has both simultaneous antimicrobial and excellent bio-integration properties, make it a promising therapeutic material for orthopedic application.

  14. Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes.

    PubMed

    Cho, Sang Soo; Aminian, Kelly; Li, Crystal; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2017-01-01

    Fatigue is a common and disabling non-motor symptom in Parkinson's disease associated with a feeling of overwhelming lack of energy. The aim of this study was to identify the neural substrates that may contribute to the development of fatigue in Parkinson's disease. Twenty-three Parkinson's disease patients meeting UK Brain Bank criteria for the diagnosis of idiopathic Parkinson's disease were recruited and completed the 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)-PET scan. The metabolic activities of Parkinson's disease patients with fatigue were compared to those without fatigue using statistical parametric mapping analysis. The Parkinson's disease group exhibiting higher level of fatigue showed anti-correlated metabolic changes in cortical regions associated with the salience (i.e., right insular region) and default (i.e., bilateral posterior cingulate cortex) networks. The metabolic abnormalities detected in these brain regions displayed a significant correlation with level of fatigue and were associated with a disruption of the functional correlations with different cortical areas. These observations suggest that fatigue in Parkinson's disease may be the expression of metabolic abnormalities and impaired functional interactions between brain regions linked to the salience network and other neural networks. Hum Brain Mapp 38:283-292, 2017. © 2016 Wiley Periodicals, Inc.

  15. Static and dynamic (18) FDG-PET in normal hispaniolan Amazon parrots (Amazona ventralis).

    PubMed

    Souza, Marcy J; Wall, Jonathan S; Stuckey, Alan; Daniel, Gregory B

    2011-01-01

    Positron emission tomography (PET) is often used to stage and monitor human cancer and has recently been used in a similar fashion in veterinary medicine. The most commonly used radiopharmaceutical is 2-Deoxy-2-[(18) F]-Fluoro-d-glucose ((18) F-FDG), which is concentrated and trapped within cells that use glucose as their energy substrate. We characterized the normal distribution of (18) F-FDG in 10 healthy Hispaniolan Amazon parrots (Amazona ventralis) by performing whole body PET scans at steady state, 60min after injection. Significant variability was found in the intestinal activity. Avian species are known to reflux fluid and electrolytes from their cloaca into their colon. To evaluate reflux as the cause of variability in intestinal distribution of (18) F-FDG, dynamic PET scans were performed on the coelomic cavity of six Hispaniolan Amazon parrots from time 0 to 60min postinjection of radiotracer. Reflux of radioactive material from the cloaca into the colon occurred in all birds to varying degrees and occurred before 60min. To evaluate the intestinal tract of clinical avian patients, dynamic scans must be performed starting immediately after injection so that increased radioactivity due to metabolism or hypermetabolic lesions such as cancer can be differentiated from increased radioactivity due to reflux of fluid from the cloaca.

  16. The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma

    NASA Astrophysics Data System (ADS)

    Thiele, Frank; Ehmer, Julia; Piroth, Marc D.; Eble, Michael J.; Coenen, Heinz H.; Kaiser, Hans-Juergen; Schaefer, Wolfgang M.; Buell, Ulrich; Boy, Christian

    2009-09-01

    The PET tracer O-(2-[18F]Fluoroethyl)-l-tyrosine (FET) has been shown to be valuable for different roles in the management of brain tumours. The aim of this study was to evaluate several quantitative measures of dynamic FET PET imaging in patients with resected glioblastoma. We evaluated dynamic FET PET in nine patients with histologically confirmed glioblastoma. Following FET PET, all subjects had radiation and chemotherapy. Tumour ROIs were defined by a threshold-based region-growing algorithm. We compared several standard measures of tumour uptake and uptake kinetics: SUV, SUV/background, distribution volume ratio (DVR), weighted frame differences and compartment model parameters. These measures were correlated with disease-free and overall survival, and analysed for statistical significance. We found that several measures allowed robust quantification. SUV and distribution volume did not correlate with clinical outcome. Measures that are based on a background region (SUV/BG, Logan-DVR) highly correlated with disease-free survival (r = -0.95, p < 0.0001), but not overall survival. Some advanced measures also showed a prognostic value but no improvement over the simpler methods. We conclude that FET PET probably has a prognostic value in patients with resected glioblastoma. The ratio of SUV to background may provide a simple and valuable predictive measure of the clinical outcome. Further studies are needed to confirm these explorative results.

  17. Correlation between FDG/PET, histology, characteristics, and survival in 332 patients with chronic lymphoid leukemia

    PubMed Central

    Falchi, Lorenzo; Keating, Michael J.; Marom, Edith M.; Truong, Mylene T.; Schlette, Ellen J.; Sargent, Rachel L.; Trinh, Long; Wang, Xuemei; Smith, Susan C.; Jain, Nitin; Estrov, Zeev; O’Brien, Susan; Wierda, William G.; Lerner, Susan

    2014-01-01

    Richter syndrome (RS) is associated with poor outcome. The prognosis of patients with histologically aggressive chronic lymphocytic leukemia (CLL), or HAC, has not been studied. We aimed to correlate 2-deoxy-2-[18F]fluoroglucose/positron emission tomography (FDG/PET) data, histological diagnosis, clinical characteristics, and survival in patients with CLL. A total of 332 patients with CLL were histologically classified as: 95 RS, 117 HAC, and 120 histologically indolent CLL (HIC). HAC and RS patients had higher maximum standardized uptake value (SUVmax), more frequent constitutional symptoms, poorer performance status (PS), lower hemoglobin and platelets, and higher lactate dehydrogenase and β-2-microglobulin. An SUVmax ≥10 strongly correlated with mortality (overall survival [OS], 56.7 vs 6.9 months in patients with SUVmax <10 vs ≥10). Survival of patients with RS and HAC was similar among patients with SUVmax <10 or ≥10. SUVmax ≥10, PS ≥2, bulky disease, and age ≥65 were independently associated with shorter OS. In patients undergoing both fine-needle aspiration and biopsy, the former proved diagnostically inadequate in 23%, 29%, and 53% of HIC, HAC, and RS, respectively. FDG/PET is a useful diagnostic tool in patients with CLL and suspected transformation. Patients with HAC show different characteristics and worse prognosis compared with those with HIC. Patients with different CLL phases, but similar SUVmax have similar outcome. Tissue biopsy should be preferred for diagnosing RS. PMID:24615780

  18. Correlation between FDG/PET, histology, characteristics, and survival in 332 patients with chronic lymphoid leukemia.

    PubMed

    Falchi, Lorenzo; Keating, Michael J; Marom, Edith M; Truong, Mylene T; Schlette, Ellen J; Sargent, Rachel L; Trinh, Long; Wang, Xuemei; Smith, Susan C; Jain, Nitin; Estrov, Zeev; O'Brien, Susan; Wierda, William G; Lerner, Susan; Ferrajoli, Alessandra

    2014-05-01

    Richter syndrome (RS) is associated with poor outcome. The prognosis of patients with histologically aggressive chronic lymphocytic leukemia (CLL), or HAC, has not been studied. We aimed to correlate 2-deoxy-2-[(18)F]fluoroglucose/positron emission tomography (FDG/PET) data, histological diagnosis, clinical characteristics, and survival in patients with CLL. A total of 332 patients with CLL were histologically classified as: 95 RS, 117 HAC, and 120 histologically indolent CLL (HIC). HAC and RS patients had higher maximum standardized uptake value (SUVmax), more frequent constitutional symptoms, poorer performance status (PS), lower hemoglobin and platelets, and higher lactate dehydrogenase and β-2-microglobulin. An SUVmax ≥10 strongly correlated with mortality (overall survival [OS], 56.7 vs 6.9 months in patients with SUVmax <10 vs ≥10). Survival of patients with RS and HAC was similar among patients with SUVmax <10 or ≥10. SUVmax ≥10, PS ≥2, bulky disease, and age ≥65 were independently associated with shorter OS. In patients undergoing both fine-needle aspiration and biopsy, the former proved diagnostically inadequate in 23%, 29%, and 53% of HIC, HAC, and RS, respectively. FDG/PET is a useful diagnostic tool in patients with CLL and suspected transformation. Patients with HAC show different characteristics and worse prognosis compared with those with HIC. Patients with different CLL phases, but similar SUVmax have similar outcome. Tissue biopsy should be preferred for diagnosing RS.

  19. Review of clinically accessible methods to determine lean body mass for normalization of standardized uptake values.

    PubMed

    Devriese, Joke; Beels, Laurence; Maes, Alex; Van De Wiele, Christophe; Gheysens, Olivier; Pottel, Hans

    2016-03-01

    With the routine use of 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans, metabolic activity of tumors can be quantitatively assessed through calculation of SUVs. One possible normalization parameter for the standardized uptake value (SUV) is lean body mass (LBM), which is generally calculated through predictive equations based on height and body weight. (Semi-)direct measurements of LBM could provide more accurate results in cancer populations than predictive equations based on healthy populations. In this context, four methods to determine LBM are reviewed: bioelectrical impedance analysis, dual-energy X-ray absorptiometry. CT, and magnetic resonance imaging. These methods were selected based on clinical accessibility and are compared in terms of methodology, precision and accuracy. By assessing each method's specific advantages and limitations, a well-considered choice of method can hopefully lead to more accurate SUVLBM values, hence more accurate quantitative assessment of 18F-FDG PET images.

  20. Sulfonation of Tyrosine as a Method to Improve Biodistribution of Peptide-Based Radiotracers: Novel (18)F-Labelled Cyclic RGD Analogues.

    PubMed

    Haskali, Mohammad Baqir; Denoyer, Delphine; Noonan, Wayne; Cullinane, Carleen; Rangger, Christine; Pouliot, Normand; Haubner, Roland; Roselt, Peter D; Hicks, Rodney J; Hutton, Craig A

    2017-02-13

    The labeling of peptides with positron emitting radionuclides has long held the promise of a wide range of PET agents possessing high affinity and selectivity. Not surprisingly, controlling the biodistribution of these agents has proven to be a major challenge in their successful application. Modification of peptide hydrophilicity in order to increase renal clearance has been a common endeavor to improve overall biodistribution. Herein, we examine the effect of site-specific sulfonation of tyrosine moieties in cyclic(RGDyK) peptides as a means to enhance their hydrophilicity and improve their biodistribution. The novel sulfonated cyclic(RGDyK) peptides were conjugated directly to 4-nitrophenyl 2-[18F]fluoropropionate and the biodistribution of the radiolabeled peptides was compared with that of their non-sulfonated, clinically relevant counterparts, [18F]GalactoRGD and [18F]FPPRGD2. Site-specific sulfonation of the tyrosine residues was shown to increase hydrophilicity and improve biodistribution of the RGD peptides, despite contributing just 79 Da towards the MW, compared with 189 Da for both the 'Galacto' and mini-PEG moieties, suggesting this may be a broadly applicable approach to enhancing biodistribution of radiolabelled peptides.

  1. 3D registration of micro PET-CT for measurable correlates of dyspeptic symptoms in mice

    NASA Astrophysics Data System (ADS)

    Camp, Jon; Simpson, Kathryn; Bardsley, Michael R.; Popko, Laura N.; Young, David L.; Kemp, Bradley J.; Lowe, Val; Ordog, Tamas; Robb, Richard

    2009-02-01

    Patients with chronic calorie insufficiency commonly suffer from upper gastrointestinal dysfunction and consequent dyspeptic symptoms, which may interfere with their nutritional rehabilitation. To investigate the relationship between gastric dysfunction and feeding behavior, we exposed mice to chronic caloric restriction and demonstrated gastric motor abnormalities in them. Gastric dysmotility is typically associated with dyspeptic symptoms but sensations cannot be directly assessed in animal models. Therefore, as an initial step toward establishing measurable correlates of postprandial symptoms in small animals, we have attempted to characterize central responses to food intake by positron emission tomography-computerized microtomography (PET-CT) in normal and calorically restricted mice. Animals consumed a standard test meal after an overnight fast before receiving 2-deoxy-2[18F]fluoro-D-glucose tracer. The same mice were also scanned in the fasting state on a separate day. We were able to bring the fed and fasting PET volume images into spatial registration with each other and with an MR-derived atlas of the mouse brain, so that the differences in uptake between the two states could be mapped quantitatively against the neuroanatomic regions of the atlas. Our approach is suitable for studying the effects of gastric dysmotilities on central responses to feeding.

  2. Positron Emission Tomography Imaging of Tumor Cell Metabolism and Application to Therapy Response Monitoring

    PubMed Central

    Challapalli, Amarnath; Aboagye, Eric O.

    2016-01-01

    Cancer cells do reprogram their energy metabolism to enable several functions, such as generation of biomass including membrane biosynthesis, and overcoming bioenergetic and redox stress. In this article, we review both established and evolving radioprobes developed in association with positron emission tomography (PET) to detect tumor cell metabolism and effect of treatment. Measurement of enhanced tumor cell glycolysis using 2-deoxy-2-[18F]fluoro-D-glucose is well established in the clinic. Analogs of choline, including [11C]choline and various fluorinated derivatives are being tested in several cancer types clinically with PET. In addition to these, there is an evolving array of metabolic tracers for measuring intracellular transport of glutamine and other amino acids or for measuring glycogenesis, as well as probes used as surrogates for fatty acid synthesis or precursors for fatty acid oxidation. In addition to providing us with opportunities for examining the complex regulation of reprogramed energy metabolism in living subjects, the PET methods open up opportunities for monitoring pharmacological activity of new therapies that directly or indirectly inhibit tumor cell metabolism. PMID:26973812

  3. Use of 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography to Aid in Diagnosing Intestinal Adenocarcinoma in 2 Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Caporizzo, Debra J; Kwiatkowski, Anna E; Chen, Ming-Kai; Beck, Amanda P; Booth, Carmen J; Zeiss, Caroline; Smith, Peter C; Scholz, Jodi A Carlson; Wilson, Steven R

    2014-01-01

    Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[18F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography–CT (FDG-PET–CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET–CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates. PMID:24956213

  4. MicroPET-based pharmacokinetic analysis of the radiolabeled boron compound [18F]FBPA-F in rats with F98 glioma.

    PubMed

    Chen, J C; Chang, S M; Hsu, F Y; Wang, H E; Liu, R S

    2004-11-01

    Boron neutron capture therapy (BNCT) is one of the effective methods of radiation therapy for the treatment of tumors such as malignant glioma. Boronophenylalanine ((10)B-BPA) solution has been used as a potential boron carrier for such a treatment. The aim of this study is to investigate 4-borono-2-[(18)F]-fluoro-l-phenylalanine-fructose ([(18)F]FBPA-F) in rats injected in the brain with glioma using in vivo small animal positron emission tomography (PET) imaging (microPET). Male Fischer 344 rats with F98 glioma in the left brain were used for these studies. Dynamic PET imaging of [(18)F]FBPA-F was performed on the 13th day after tumor inoculation. Arterial blood sampling was performed to obtain an input function for tracer kinetic modeling. The accumulation ratios of [(18)F]FBPA-F for the glioma-to-normal brain approached 3. The uptake characteristics of BPA-F and [(18)F]FBPA-F were similar. The results indicate that 4h after BPA-F injection would be the optimal irradiation time for BNCT. Rate constants were estimated using a three-compartment model. This study provides useful information for the clinical application of BNCT in patients with brain tumors.

  5. Molecular imaging of therapy response with 18F-FLT and 18F-FDG following cyclophosphamide and mTOR inhibition

    PubMed Central

    Saint-Hubert, Marijke De; Brepoels, Lieselot; Devos, Ellen; Vermaelen, Peter; Groot, Tjibe De; Tousseyn, Thomas; Mortelmans, Luc; Mottaghy, Felix M

    2012-01-01

    Purpose Evaluation and comparison of 3’-[18F]-fluoro-3’-deoxy-L-thymidine (FLT) and 2-[18F]-fluoro-2-deoxyglucose (FDG)-PET to monitor early response following both cyclophosphamide and temsirolimus treatment in a mouse model of Burkitt lymphoma. Methods Daudi xenograft mice were treated with either cyclophosphamide or temsirolimus and imaged with FLT-PET and FDG-PET on appropriate days post therapy inititiation. Immunohistochemical (IHC) studies (H&E, TUNEL, CD20, PCNA and ki-67) and DNA flow cytometry studies were performed. Results FDG tumor uptake decreased immediately after cyclophosphamide treatment while FLT-PET showed only a late and less pronounced decrease. A fast induction of apoptosis was observed together with an early accumulation of cells in the S-phase of the cell cycle, suggesting DNA repair. Temsirolimus treatment reduced both FDG and FLT tumor uptake immediately after therapy and resulted in a fast induction of apoptosis and G0-G1 phase accumulation. Conclusion FLT response was less distinct than FDG response and may be controlled by DNA repair early after cyclophosphamide. Nevertheless, FLT-PET was able to reflect decreased proliferation following temsirolimus. PMID:23133806

  6. Low-Dose PET/CT and Full-Dose Contrast-Enhanced CT at the Initial Staging of Localized Diffuse Large B-Cell Lymphomas

    PubMed Central

    Sabaté-Llobera, Aida; Cortés-Romera, Montserrat; Mercadal, Santiago; Hernández-Gañán, Javier; Pomares, Helena; González-Barca, Eva; Gámez-Cenzano, Cristina

    2016-01-01

    Computed tomography (CT) has been used as the reference imaging technique for the initial staging of diffuse large B-cell lymphoma until recent days, when the introduction of positron emission tomography (PET)/CT imaging as a hybrid technique has become of routine use. However, the performance of both examinations is still common. The aim of this work was to compare the findings between low-dose 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) PET/CT and full-dose contrast-enhanced CT (ceCT) in 28 patients with localized diffuse large B-cell lymphoma according to PET/CT findings, in order to avoid the performance of ceCT. For each technique, a comparison in the number of nodal and extranodal involved regions was performed. PET/CT showed more lesions than ceCT in both nodal (41 vs. 36) and extranodal localizations (16 vs. 15). Disease staging according to both techniques was concordant in 22 patients (79%) and discordant in 6 patients (21%), changing treatment management in 3 patients (11%). PET/CT determined a better staging and therapeutic approach, making the performance of an additional ceCT unnecessary. PMID:27559300

  7. Weight gain following subthalamic nucleus deep brain stimulation: a PET study.

    PubMed

    Sauleau, Paul; Le Jeune, Florence; Drapier, Sophie; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Lalys, Florent; Robert, Gabriel; Drapier, Dominique; Vérin, Marc

    2014-12-01

    Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]-IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m(2) (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease.

  8. New developments of dopaminergic imaging in Parkinson's disease.

    PubMed

    Varrone, A; Halldin, C

    2012-03-09

    The development of radioligands for the dopaminergic system has provided suitable imaging biomarkers for clinical research in Parkinson's disease (PD) and related movement disorders. Single photon emission tomography (SPECT) has played an important role as main molecular imaging modality because of the availability of imaging tools such as dopamine transporter (DAT) radioligands for wide clinical use. At present, SPECT imaging of the DAT is the main diagnostic imaging procedure for the assessment of patients with parkinsonism. However, in the recent years positron emission tomography (PET) has become an important clinical diagnostic modality, mainly in oncology, due to the wide availability of PET/CT systems with improved imaging performance and to the use of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as main diagnostic agent. In this context, further development of 18F-radioligands is of high interest for their potential utility in the clinical setting. This review will give a general overview on the development of SPECT and PET radioligands for the dopaminergic system and describe the potential advantages of developing 18F-labelled radioligands for imaging of the dopaminergic system in PD and related movement disorders.

  9. New developments of dopaminergic imaging in Parkinson's disease.

    PubMed

    Varrone, A; Halldin, C

    2012-02-01

    The development of radioligands for the dopaminergic system has provided suitable imaging biomarkers for clinical research in Parkinson's disease (PD) and related movement disorders. Single photon emission tomography (SPECT) has played an important role as main molecular imaging modality because of the availability of imaging tools such as dopamine transporter (DAT) radioligands for wide clinical use. At present, SPECT imaging of the DAT is the main diagnostic imaging procedure for the assessment of patients with parkinsonism. However, in the recent years positron emission tomography (PET) has become an important clinical diagnostic modality, mainly in oncology, due to the wide availability of PET/CT systems with improved imaging performance and to the use of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as main diagnostic agent. In this context, further development of 18F-radioligands is of high interest for their potential utility in the clinical setting. This review will give a general overview on the development of SPECT and PET radioligands for the dopaminergic system and describe the potential advantages of developing 18F-labelled radioligands for imaging of the dopaminergic system in PD and related movement disorders.

  10. Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

    PubMed

    Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

    2016-01-01

    Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

  11. Application of feedback-controlled bolus plus infusion (FC-B/I) method for quantitative PET imaging of dopamine transporters with [(18)F]β-CFT-FE in conscious monkey brain.

    PubMed

    Harada, Norihiro; Ohba, Hiroyuki; Kakiuchi, Takeharu; Tsukada, Hideo

    2013-01-01

    The competitive inhibition of dopamine transporters (DAT) with cocaine, a specific DAT inhibitor, was evaluated with a feedback-controlled bolus plus infusion (FC-B/I) method using animal positron emission tomography (PET) in the living brain of conscious monkey. 2β-Carbomethoxy-3β-(4-fluorophenyl)-8-(2-[(18)F]fluoroethyl) nortropane ([(18)F]β-CFT-FE; Harada et al. [2004] Synapse 54:37-45) was used for this study because it provided specific, fast, and reversible kinetic properties to DAT in the striatum. In FC-B/I method, the real-time image reconstruction was started just after intravenous bolus injection of [(18)F]β-CFT-FE to generate a time-activity curve in the striatum, and the infusion rate was adjusted to achieve an equilibrium state of the striatal radioactivity concentrations by means of a feedback-control algorithm. The first equilibrium state in the brain was reached within 20 min after the infusion start. Intravenous administration of cocaine at the doses of 0.02, 0.1, and 0.5 mg/kg shifted the equilibrium radioactivity level to the second equilibrium state in a dose-dependent manner, while no significant alterations was observed in the cerebellum. The present results demonstrated that the combined use of FC-B/I method and PET probe with fast kinetics like [(18)F]β-CFT-FE could be useful to assess the occupancy of drugs in the living brain with PET.

  12. Use of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography to aid in diagnosing intestinal adenocarcinoma in 2 rhesus macaques (Macaca mulatta).

    PubMed

    Caporizzo, Debra J; Kwiatkowski, Anna E; Chen, Ming-Kai; Beck, Amanda P; Booth, Carmen J; Zeiss, Caroline; Smith, Peter C; Carlson Scholz, Jodi A; Wilson, Steven R

    2014-06-01

    Two aged female rhesus macaques (Macaca mulatta) presented with weight loss and intermittent inappetence. The signalment and constellation of clinical signs led clinicians to suspect the presence of intestinal adenocarcinoma. Because of each animal's advanced age and inconclusive radiographic findings, a noninvasive diagnostic tool was preferred over exploratory laparotomy to assist in determining a diagnosis. Consequently, 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-CT (FDG-PET-CT) was chosen to aid in confirming a suspicion of gastrointestinal adenocarcinoma in both animals. FDG is a glucose analogue labeled with fluorine-18 and is taken up by highly metabolically active cells, as observed in many cancers. Tomography revealed an annular constriction of the small intestine with focal FDG uptake in one animal, and an FDG avid transmural mass in the ascending colon of the second animal. Necropsy later confirmed both sites to be adenocarcinomas. This report supports the use of FDG-PET-CT as an adjunct to conventional radiography in the diagnosis of intestinal adenocarcinoma in nonhuman primates.

  13. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    SciTech Connect

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

  14. Endoscopic resection of esthesioneuroblastoma.

    PubMed

    Gallia, Gary L; Reh, Douglas D; Lane, Andrew P; Higgins, Thomas S; Koch, Wayne; Ishii, Masaru

    2012-11-01

    Esthesioneuroblastoma, or olfactory neuroblastoma, is an uncommon malignant tumor arising in the upper nasal cavity. Surgical approaches to this and other sinonasal malignancies involving the anterior skull base have traditionally involved craniofacial resections. Over the past 10 years to 15 years, there have been advances in endoscopic approaches to skull base pathologies, including malignant tumors. In this study, we review our experience with purely endoscopic approaches to esthesioneuroblastomas. Between January 2005 and February 2012, 11 patients (seven men and four women, average age 53.3 years) with esthesioneuroblastoma were treated endoscopically. Nine patients presented with newly diagnosed disease and two were treated for tumor recurrence. The modified Kadish staging was: A, two patients (18.2%); B, two patients (18.2%); C, five patients (45.5%); and D, two patients (18.2%). All patients had a complete resection with negative intraoperative margins. Three patients had 2-deoxy-2-((18)F)fluoro-d-glucose avid neck nodes on their preoperative positron emission tomography-CT scan. These patients underwent neck dissections; two had positive neck nodes. Perioperative complications included an intraoperative hypertensive urgency and pneumocephalus in two different patients. Mean follow-up was over 28 months and all patients were free of disease. This series adds to the growing experience of purely endoscopic surgical approaches in the treatment of skull base tumors including esthesioneuroblastoma. Longer follow-up on larger numbers of patients is required to clarify the utility of purely endoscopic approaches in the management of this malignant tumor.

  15. 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

  16. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

    PubMed Central

    Psaltis, Peter J.

    2016-01-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of 18Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of 18Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093

  17. Development of radiodetection systems towards miniaturised quality control of PET and SPECT radiopharmaceuticals.

    PubMed

    Taggart, Matthew P; Tarn, Mark D; Esfahani, Mohammad M N; Schofield, Daniel M; Brown, Nathaniel J; Archibald, Stephen J; Deakin, Tom; Pamme, Nicole; Thompson, Lee F

    2016-04-26

    The ability to detect radiation in microfluidic devices is important for the on-chip analysis of radiopharmaceuticals, but previously reported systems have largely suffered from various limitations including cost, complexity of fabrication, and insufficient sensitivity and/or speed. Here, we present the use of sensitive, low cost, small-sized, commercially available silicon photomultipliers (SiPMs) for the detection of radioactivity inside microfluidic channels fabricated from a range of conventional microfluidic chip substrates. We demonstrate the effects of chip material and thickness on the detection of the positron-emitting isotope, [(18)F]fluoride, and find that, while the SiPMs are light sensors, they are able to detect radiation even through opaque chip materials via direct positron and gamma (γ) ray interaction. Finally, we employed the SiPM platform for analysis of the PET (positron emission tomography) radiotracers 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) and [(68)Ga]gallium-citrate, and highlight the ability to detect the γ ray emitting SPECT (single photon emission computed tomography) radiotracer, [(99m)Tc]pertechnetate.

  18. Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study

    PubMed Central

    Buck, Jason R.; McKinley, Eliot T.; Fu, Allie; Abel, Ty W.; Thompson, Reid C.; Chambless, Lola; Watchmaker, Jennifer M.; Harty, James P.; Cooper, Michael K.; Manning, H. Charles

    2015-01-01

    Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes. PMID:26517124

  19. Ketones suppress brain glucose consumption.

    PubMed

    LaManna, Joseph C; Salem, Nicolas; Puchowicz, Michelle; Erokwu, Bernadette; Koppaka, Smruta; Flask, Chris; Lee, Zhenghong

    2009-01-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as beta-hydroxybutyrate (beta HB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet). In this study, the local cerebral metabolic rate of glucose consumption (CMRglu; microM/min/100g) was calculated in the cortex and cerebellum of control and ketotic rats using Patlak analysis. Rats were imaged on a rodent PET scanner and MRI was performed on a 7-Tesla Bruker scanner for registration with the PET images. Plasma glucose and beta HB concentrations were measured and 90-minute dynamic PET scans were started simultaneously with bolus injection of 2-Deoxy-2[18F]Fluoro-D-Glucose (FDG). The blood radioactivity concentration was automatically sampled from the tail vein for 3 min following injection and manual periodic blood samples were taken. The calculated local CMRGlu decreased with increasing plasma BHB concentration in the cerebellum (CMRGlu = -4.07*[BHB] + 61.4, r2 = 0.3) and in the frontal cortex (CMRGlu = -3.93*[BHB] + 42.7, r2 = 0.5). These data indicate that, under conditions of ketosis, glucose consumption is decreased in the cortex and cerebellum by about 10% per each mM of plasma ketone bodies.

  20. Ketosis proportionately spares glucose utilization in brain.

    PubMed

    Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

    2013-08-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

  1. Dynamic functional imaging of brain glucose utilization using fPET-FDG

    DOE PAGES

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; ...

    2014-06-14

    We report that glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits themore » utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. Ultimately, this new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.« less

  2. Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging

    PubMed Central

    Fecher, David; Hofmann, Elisabeth; Buck, Andreas; Bundschuh, Ralph; Nietzer, Sarah; Dandekar, Gudrun; Walles, Thorsten; Walles, Heike; Lückerath, Katharina; Steinke, Maria

    2016-01-01

    Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and –testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future. PMID:27501455

  3. Caged [(18)F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography.

    PubMed

    Flavell, Robert R; Truillet, Charles; Regan, Melanie K; Ganguly, Tanushree; Blecha, Joseph E; Kurhanewicz, John; VanBrocklin, Henry F; Keshari, Kayvan R; Chang, Christopher J; Evans, Michael J; Wilson, David M

    2016-01-20

    Solid tumors are hypoxic with altered metabolism, resulting in secretion of acids into the extracellular matrix and lower relative pH, a feature associated with local invasion and metastasis. Therapeutic and diagnostic agents responsive to this microenvironment may improve tumor-specific delivery. Therefore, we pursued a general strategy whereby caged small-molecule drugs or imaging agents liberate their parent compounds in regions of low interstitial pH. In this manuscript, we present a new acid-labile prodrug method based on the glycosylamine linkage, and its application to a class of positron emission tomography (PET) imaging tracers, termed [(18)F]FDG amines. [(18)F]FDG amines operate via a proposed two-step mechanism, in which an acid-labile precursor decomposes to form the common radiotracer 2-deoxy-2-[(18)F]fluoro-d-glucose, which is subsequently accumulated by glucose avid cells. The rate of decomposition of [(18)F]FDG amines is tunable in a systematic fashion, tracking the pKa of the parent amine. In vivo, a 4-phenylbenzylamine [(18)F]FDG amine congener showed greater relative accumulation in tumors over benign tissue, which could be attenuated upon tumor alkalinization using previously validated models, including sodium bicarbonate treatment, or overexpression of carbonic anhydrase. This new class of PET tracer represents a viable approach for imaging acidic interstitial pH with potential for clinical translation.

  4. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    PubMed

    Mahajan, A; Goh, V; Basu, S; Vaish, R; Weeks, A J; Thakur, M H; Cook, G J

    2015-10-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure-function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [(18)F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed "theranostics". Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research.

  5. Dynamic Functional Imaging of Brain Glucose Utilization using fPET-FDG

    PubMed Central

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B.; Catana, Ciprian; Polimeni, Jonathan R.; Sander, Christin Y.; Zürcher, Nicole R.; Chonde, Daniel B.; Fowler, Joanna S.; Rosen, Bruce R.; Hooker, Jacob M.

    2014-01-01

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[18F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis is straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism. PMID:24936683

  6. Dynamic functional imaging of brain glucose utilization using fPET-FDG.

    PubMed

    Villien, Marjorie; Wey, Hsiao-Ying; Mandeville, Joseph B; Catana, Ciprian; Polimeni, Jonathan R; Sander, Christin Y; Zürcher, Nicole R; Chonde, Daniel B; Fowler, Joanna S; Rosen, Bruce R; Hooker, Jacob M

    2014-10-15

    Glucose is the principal source of energy for the brain and yet the dynamic response of glucose utilization to changes in brain activity is still not fully understood. Positron emission tomography (PET) allows quantitative measurement of glucose metabolism using 2-[(18)F]-fluorodeoxyglucose (FDG). However, FDG PET in its current form provides an integral (or average) of glucose consumption over tens of minutes and lacks the temporal information to capture physiological alterations associated with changes in brain activity induced by tasks or drug challenges. Traditionally, changes in glucose utilization are inferred by comparing two separate scans, which significantly limits the utility of the method. We report a novel method to track changes in FDG metabolism dynamically, with higher temporal resolution than exists to date and within a single session. Using a constant infusion of FDG, we demonstrate that our technique (termed fPET-FDG) can be used in an analysis pipeline similar to fMRI to define within-session differential metabolic responses. We use visual stimulation to demonstrate the feasibility of this method. This new method has a great potential to be used in research protocols and clinical settings since fPET-FDG imaging can be performed with most PET scanners and data acquisition and analysis are straightforward. fPET-FDG is a highly complementary technique to MRI and provides a rich new way to observe functional changes in brain metabolism.

  7. Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

    PubMed Central

    Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.; Pradhan, Kith; Henn, Fritz A.; Shea, Stephen; Osten, Pavel; Li, Bo

    2016-01-01

    Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses. PMID:26869888

  8. Cerebral metabolic rate for glucose during the first six months of life: an FDG positron emission tomography study.

    PubMed Central

    Kinnala, A.; Suhonen-Polvi, H.; Aärimaa, T.; Kero, P.; Korvenranta, H.; Ruotsalainen, U.; Bergman, J.; Haaparanta, M.; Solin, O.; Nuutila, P.; Wegelius, U.

    1996-01-01

    AIM: To measure the local cerebral metabolic rate for glucose (LCMRGlc) in neonatal brains during maturation using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). METHODS: Twenty infants were studied using PET during the neonatal period. The postconceptional age ranged from 32.7 to 60.3 weeks. All infants had normal neurodevelopment and were normoglycaemic. The development of the infants was carefully evaluated (follow up 12-36 months) clinically, and by using a method based on Gesell Amatruda's developmental diagnosis. LCMRGlc was quantitated using PET derived from FDG kinetics and calculated in the whole brain and for regional brain structures. RESULTS: LCMRGlc for various cortical brain regions and the basal ganglia was low at birth (from 4 to 16 mumol/100 g/minute). In infants 2 months of age and younger LCMRGlc was highest in the sensorimotor cortex, thalamus, and brain stem. By 5 months, LCMRGlc had increased in the frontal, parietal, temporal, occipital and cerebellar cortical regions. In general, the whole brain LCMRGlc correlated with postconceptional age (r = 0.90; P < 0.001). The change in the glucose metabolic pattern observed in the neonatal brain reflects the functional maturation of these brain regions. CONCLUSION: These findings show that LCMRGlc in infants increases with maturation. Accordingly, when LCMRGlc is measured during infancy, the postconceptional age has to be taken into account when interpretating the results. Images Figure 1 PMID:8777676

  9. First Quantitative Imaging of Organic Fluorine within Angiogenic Tissues by Particle Induced Gamma-Ray Emission (PIGE) Analysis: First PIGE Organic Fluorine Imaging

    PubMed Central

    Lavielle, Sébastien; Gionnet, Karine; Ortega, Richard; Devès, Guillaume; Kilarski, Victor; Wehbe, Katia; Bikfalvi, Andreas; Déléris, Gérard

    2011-01-01

    PET (Positron Emission Tomography) allows imaging of the in vivo distribution of biochemical compounds labeled with a radioactive tracer, mainly 18F-FDG (2-deoxy-2-[18F] fluoro-D-glucose). 18F only allows a relatively poor spatial resolution (2-3 mm) which does not allow imaging of small tumors or specific small size tissues, e.g. vasculature. Unfortunately, angiogenesis is a key process in various physiologic and pathologic processes and is, for instance, involved in modern anticancer approaches. Thus ability to visualize angiogenesis could allow early diagnosis and help to monitor the response of cancer to specific chemotherapies. Therefore, indirect analytical techniques are required to assess the localization of fluorinated compounds at a micrometric scale. Multimodality imaging approaches could provide accurate information on the metabolic activity of the target tissue. In this article, PIGE method (Particle Induced Gamma-ray Emission) was used to determine fluorinated tracers by the nuclear reaction of 19F(p,p′γ)19F in tissues. The feasibility of this approach was assessed on polyfluorinated model glucose compounds and novel peptide-based tracer designed for angiogenesis imaging. Our results describe the first mapping of the biodistribution of fluorinated compounds in both vascularized normal tissue and tumor tissue. PMID:24310427

  10. First Quantitative Imaging of Organic Fluorine within Angiogenic Tissues by Particle Induced Gamma-Ray Emission (PIGE) Analysis: First PIGE Organic Fluorine Imaging.

    PubMed

    Lavielle, Sébastien; Gionnet, Karine; Ortega, Richard; Devès, Guillaume; Kilarski, Victor; Wehbe, Katia; Bikfalvi, Andreas; Déléris, Gérard

    2011-03-09

    PET (Positron Emission Tomography) allows imaging of the in vivo distribution of biochemical compounds labeled with a radioactive tracer, mainly 18F-FDG (2-deoxy-2-[18F] fluoro-D-glucose). 18F only allows a relatively poor spatial resolution (2-3 mm) which does not allow imaging of small tumors or specific small size tissues, e.g. vasculature. Unfortunately, angiogenesis is a key process in various physiologic and pathologic processes and is, for instance, involved in modern anticancer approaches. Thus ability to visualize angiogenesis could allow early diagnosis and help to monitor the response of cancer to specific chemotherapies. Therefore, indirect analytical techniques are required to assess the localization of fluorinated compounds at a micrometric scale. Multimodality imaging approaches could provide accurate information on the metabolic activity of the target tissue. In this article, PIGE method (Particle Induced Gamma-ray Emission) was used to determine fluorinated tracers by the nuclear reaction of 19F(p,p'γ)19F in tissues. The feasibility of this approach was assessed on polyfluorinated model glucose compounds and novel peptide-based tracer designed for angiogenesis imaging. Our results describe the first mapping of the biodistribution of fluorinated compounds in both vascularized normal tissue and tumor tissue.

  11. Long-term cilostazol administration ameliorates memory decline in senescence-accelerated mouse prone 8 (SAMP8) through a dual effect on cAMP and blood-brain barrier.

    PubMed

    Yanai, Shuichi; Toyohara, Jun; Ishiwata, Kiichi; Ito, Hideki; Endo, Shogo

    2017-04-01

    Phosphodiesterases (PDEs), which hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP), play an important role in synaptic plasticity that underlies memory. Recently, several PDE inhibitors were assessed for their possible therapeutic efficacy in treating cognitive disorders. Here, we examined how cilostazol, a selective PDE3 inhibitor, affects brain functions in senescence-accelerated mouse prone 8 (SAMP8), an animal model of age-related cognitive impairment. Long-term administration of cilostazol restored the impaired context-dependent conditioned fear memory of SAMP8 to match that in normal aging control substrain SAMR1. Cilostazol also increased the number of cells containing phosphorylated cAMP-responsive element binding protein (CREB), a downstream component of the cAMP pathway. Finally, cilostazol improves blood-brain barrier (BBB) integrity, demonstrated by reduced extravasation of 2-deoxy-2-(18)F-fluoro-d-glucose and Evans Blue dye in the brains of SAMP8. This improvement in BBB integrity was associated with an increased amount of zona occludens protein 1 (ZO-1) and occludin proteins, components of tight junctions integral to the BBB. The results suggest that long-term administration of cilostazol exerts its beneficial effects on age-related cognitive impairment through a dual mechanism: by enhancing the cAMP system in the brain and by maintaining or improving BBB integrity.

  12. Niobium sputtered Havar foils for the high-power production of reactive [18F]fluoride by proton irradiation of [18O]H2O targets.

    PubMed

    Wilson, J S; Avila-Rodriguez, M A; Johnson, R R; Zyuzin, A; McQuarrie, S A

    2008-05-01

    Niobium sputtered Havar entrance foils were used for the production of reactive [(18)F]fluoride by proton irradiation of [(18)O]H(2)O targets under pressurized conditions. The synthesis yield in the routine production of 2-[(18)F]fluoro-2-deoxy-glucose (FDG) was used as an indicative parameter of the reactivity of (18)F. The yield of FDG obtained with (18)F produced in a target with Havar foil was used as a baseline. No statistically significant difference was found in the saturated yields of (18)F when using Havar or Havar-Nb sputtered entrance foils. However, the amount of long-lived radionuclidic impurities decreased more than 10-fold using the Havar-Nb entrance foil. The average decay corrected synthesis yield of FDG, evaluated over a period of more than 2 years, was found to be approximately 5% higher when using a Havar-Nb entrance foil and a marked improvement on the FDG yield consistency was noted. In addition, the frequency of target rebuilding was greatly diminished when using the Nb sputtered entrance foil.

  13. Effect of Harderian adenectomy on the statistical analyses of mouse brain imaging using positron emission tomography

    PubMed Central

    Kim, Minsoo; Woo, Sang-Keun; Yu, Jung Woo; Lee, Yong Jin; Kim, Kyeong Min; Kang, Joo Hyun; Eom, Kidong

    2014-01-01

    Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains. PMID:23820224

  14. Reproducibility of Static and Dynamic 18F-FDG, 18F-FLT, and 18F-FMISO MicroPET Studies in a Murine Model of HER2+ Breast Cancer

    PubMed Central

    Whisenant, Jennifer G.; Peterson, Todd E.; Fluckiger, Jacob U.; Tantawy, Mohammed Noor; Ayers, Gregory D.; Yankeelov, Thomas E.

    2013-01-01

    Purpose The objective of this study is to determine the reproducibility of static 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]-fluoromisonidazole (18F-FMISO) microPET measurements, as well as kinetic parameters returned from analyses of dynamic 18F-FLT and 18F-FMISO data. Procedures HER2+ xenografts were established in nude mice. Dynamic data were acquired for 60 min, followed by a repeat injection and second scan 6 h later. Reproducibility was assessed for the percent-injected dose per gram (%ID/g) for each radiotracer, and with kinetic parameters (K1–k4, Ki) for 18F-FLT and 18F-FMISO. Results The value needed to reflect a change in tumor physiology is given by the 95 % confidence interval (CI), which is ±14, ±5, and ±6 % for 18F-FDG (n=12), 18F-FLT (n=11), and 18F-FMISO (n=11) %ID/g, respectively. Vd (=K1/k2), k3, and KFLT are the most reproducible 18F-FLT (n=9) kinetic parameters, with 95 % CIs of ±18, ±10, and ±18 %, respectively. Vd and KFMISO are the most reproducible 18F-FMISO kinetic parameters (n=7) with 95 % CIs of ±16 and ±14 %, respectively. Conclusions Percent-injected dose per gram measurements are reproducible and appropriate for detecting treatment-induced changes. Kinetic parameters have larger threshold values, but are potentially sufficiently reproducible to detect treatment response. PMID:22644988

  15. First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with 68Ga-NODAGA-THERANOST, a High-Affinity Peptidomimetic for αvβ3 Integrin Receptor Targeting

    PubMed Central

    Baum, Richard P.; Kulkarni, Harshad R.; Müller, Dirk; Danthi, Narasimhan; Kim, Young-Seung; Brechbiel, Martin W.

    2015-01-01

    Abstract 68Ga-NODAGA-THERANOST™ is an αvβ3 integrin antagonist and the first radiolabeled peptidomimetic to reach clinical development for targeting integrin receptors. In this first-in-human study, the feasibility of integrin receptor peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging was confirmed in patients with non-small-cell lung cancer and breast cancer. Methods: Patients underwent PET/CT imaging with 68Ga NODAGA-THERANOST. PET images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2-(18F) fluoro-d-glucose (18F-FDG) findings. Images were obtained 60 minutes postinjection of 300–500 MBq of 68Ga-NODAGA-THERANOST. Results: 68Ga-NODAGA-THERANOST revealed high tumor-to-background ratios (SUVmax=4.8) and uptake at neoangiogenesis sites. Reconstructed fused images distinguished cancers with high malignancy potential and enabled enhanced bone metastasis detection. 18F-FDG-positive lung and lymph node metastases did not show uptake, indicating the absence of neovascularization. Conclusions: 68Ga-NODAGA-THERANOST was found to be safe and effective, exhibiting in this study rapid blood clearance, stability, rapid renal excretion, favorable biodistribution and PK/PD, low irradiation burden (μSv/MBq/μg), and convenient radiolabeling. This radioligand might enable theranostics, that is, a combination of diagnostics followed by the appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical assessment, treatment response evaluation, prediction of pathologic response, neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine strategies. Further clinical trials evaluating 68Ga-NODAGA-THERANOST are warranted. PMID:25945808

  16. Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

    PubMed Central

    Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2016-01-01

    The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain. PMID:27440054

  17. Radiosynthesis and 'click' conjugation of ethynyl-4-[(18)F]fluorobenzene--an improved [(18)F]synthon for indirect radiolabeling.

    PubMed

    Roberts, Maxine P; Pham, Tien Q; Doan, John; Jiang, Cathy D; Hambley, Trevor W; Greguric, Ivan; Fraser, Benjamin H

    2015-01-01

    Reproducible methods for [(18)F]radiolabeling of biological vectors are essential for the development of new [(18)F]radiopharmaceuticals. Molecules such as carbohydrates, peptides and proteins are challenging substrates that often require multi-step indirect radiolabeling methods. With the goal of developing more robust, time saving, and less expensive procedures for indirect [(18)F]radiolabeling of such molecules, our group has synthesized ethynyl-4-[(18)F]fluorobenzene ([(18)F]2, [(18)F]EYFB) in a single step (14 ± 2% non-decay corrected radiochemical yield (ndc RCY)) from a readily synthesized, shelf stable, inexpensive precursor. The alkyne-functionalized synthon [(18)F]2 was then conjugated to two azido-functionalized vector molecules via CuAAC reactions. The first 'proof of principle' conjugation of [(18)F]2 to 1-azido-1-deoxy-β-D-glucopyranoside (3) gave the desired radiolabeled product [(18)F]4 in excellent radiochemical yield (76 ± 4% ndc RCY (11% overall)). As a second example, the conjugation of [(18)F]2 to matrix-metalloproteinase inhibitor (5), which has potential in tumor imaging, gave the radiolabeled product [(18)F]6 in very good radiochemical yield (56 ± 12% ndc RCY (8% overall)). Total preparation time for [(18)F]4 and [(18)F]6 including [(18)F]F(-) drying, two-step reaction (nucleophilic substitution and CuAAC conjugation), two HPLC purifications, and two solid phase extractions did not exceed 70 min. The radiochemical purity of synthon [(18)F]2 and the conjugated products, [(18)F]4 and [(18)F]6, were all greater than 98%. The specific activities of [(18)F]2 and [(18)F]6 were low, 5.97 and 0.17 MBq nmol(-1), respectively.

  18. Synthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors.

    PubMed

    Vala, Christine; Morley, Thomas J; Zhang, Xuechun; Papin, Caroline; Tavares, Adriana Alexandre S; Lee, H Sharon; Constantinescu, Cristian; Barret, Olivier; Carroll, Vincent M; Baldwin, Ronald M; Tamagnan, Gilles D; Alagille, David

    2016-09-06

    Imaging agents that target adenosine type 2A (A2A ) receptors play an important role in evaluating new pharmaceuticals targeting these receptors, such as those currently being developed for the treatment of movement disorders like Parkinson's disease. They are also useful for monitoring progression and treatment efficacy by providing a noninvasive tool to map changes in A2A receptor density and function in neurodegenerative diseases. We previously described the successful evaluation of two A2A -specific radiotracers in both nonhuman primates and in subsequent human clinical trials: [(123) I]MNI-420 and [(18) F]MNI-444. Herein we describe the development of both of these radiotracers by selection from a series of A2A ligands, based on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine core of preladenant. Each of this series of 16 ligands was found to bind to recombinant human A2A receptor in the low nanomolar range, and of these 16, six were radiolabeled with either fluorine-18 or iodine-123 and evaluated in nonhuman primates. These initial in vivo results resulted in the identification of 7-(2-(4-(4-(2-[(18) F]fluoroethoxy)phenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine ([(18) F]MNI-444) and 7-(2-(4-(2-fluoro-4-[(123) I]iodophenyl)piperazin-1-yl)ethyl)-2-(furan-2-yl)-7H-imidazo[1,2-c]pyrazolo[4,3-e]pyrimidin-5-amine ([(123) I]MNI-420) as PET and SPECT radiopharmaceuticals for mapping A2A receptors in brain.

  19. H-CRRETAWAC-OH, a Lead Structure for the Development of Radiotracer Targeting Integrin α5β1?

    PubMed Central

    Maschauer, Simone; Einsiedel, Jürgen; Eder, Iris E.; Gmeiner, Peter; Virgolini, Irene J.

    2014-01-01

    Imaging of angiogenic processes is of great interest in preclinical research as well as in clinical settings. The most commonly addressed target structure for imaging angiogenesis is the integrin αvβ3. Here we describe the synthesis and evaluation of [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH, a radiolabelled peptide designed to selectively target the integrin α5β1. Conjugation of 4-nitrophenyl-(RS)-2-[18F]fluoropropionate provided [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH in high radiochemical purity (>95%) and a radiochemical yield of approx. 55%. In vitro evaluation showed α5β1 binding affinity in the nanomolar range, whereas affinity to αvβ3 and αIIbβ3 was >50 μM. Cell uptake studies using human melanoma M21 (αvβ3-positive andα5β1-negative), human melanoma M21-L (αvβ3-negative and α5β1-negative), and human prostate carcinoma DU145 (αvβ3-negative and α5β1-positive) confirmed receptor-specific binding. The radiotracer was stable in human serum and showed low protein binding. Biodistribution studies showed tumour uptake ranging from 2.5 to 3.5% ID/g between 30 and 120 min post-injection. However, blocking studies and studies using mice bearing α5β1-negative M21 tumours did not confirm receptor-specific uptake of [18F]FProp-Cys*-Arg-Arg-Glu-Thr-Ala-Trp-Ala-Cys*-OH, although this radiopeptide revealed high affinity and substantial selectivity to α5β1 in vitro. Further experiments are needed to study the in vivo metabolism of this peptide and to develop improved radiopeptide candidates suitable for PET imaging of α5β1 expression in vivo. PMID:25374888

  20. Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT.

    PubMed

    Yeh, Hsin Hsien; Ogawa, Kazuma; Balatoni, Julius; Mukhapadhyay, Uday; Pal, Asutosh; Gonzalez-Lepera, Carlos; Shavrin, Aleksandr; Soghomonyan, Suren; Flores, Leo; Young, Daniel; Volgin, Andrei Y; Najjar, Amer M; Krasnykh, Victor; Tong, William; Alauddin, Mian M; Gelovani, Juri G

    2011-01-25

    The importance of the EGF receptor (EGFR) signaling pathway in the development and progression of nonsmall cell lung carcinomas (NSCLC) is widely recognized. Gene sequencing studies revealed that a majority of tumors responding to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. This underscores the need for novel biomarkers and diagnostic imaging approaches to identify patients who may benefit from particular therapeutic agents and approaches with improved efficacy and safety profiles. To this goal, we developed 4-[(3-iodophenyl)amino]-7-{2-[2-{2-(2-[2-{2-([(18)F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide ([(18)F]F-PEG6-IPQA), a radiotracer with increased selectivity and irreversible binding to the active mutant L858R EGFR kinase. We show that PET with [(18)F]F-PEG6-IPQA in tumor-bearing mice discriminates H3255 NSCLC xenografts expressing L858R mutant EGFR from H441 and PC14 xenografts expressing EGFR or H1975 xenografts with L858R/T790M dual mutation in EGFR kinase domain, which confers resistance to EGFR inhibitors (i.e., gefitinib). The T790M mutation precludes the [(18)F]F-PEG6-IPQA from irreversible binding to EGFR. These results suggest that PET with [(18)F]F-PEG6-IPQA could be used for the selection of NSCLC patients for individualized therapy with small molecular inhibitors of EGFR kinase that are currently used in the clinic and have a similar structure (i.e., iressa, gefitinib, and erlotinib).

  1. Improving 18F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography Imaging in Alzheimer's Disease Studies

    PubMed Central

    Knešaurek, Karin

    2015-01-01

    The goal was to improve Alzheimer's 2-deoxy-2-18F-fluoro-D-glucose (18F FDG)-positron emission tomography (PET)/computed tomography (CT) imaging through application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT) restoration technique, in order to provide earlier and more accurate clinical results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice system was used to acquire studies. Patient data were acquired according the Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented Fourier-wavelet regularized restoration, with a Butterworth low-pass filter, order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet (Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET-R) ADNI subject PET images were compared using the Alzheimer's discrimination analysis by dedicated software. Forty-two PET/CT scans were used in the study. They were performed on eleven ADNI subjects at intervals of approximately 6 months. The final clinical diagnosis was used as a gold standard. For three subjects, the final clinical diagnosis was mild cognitive impairment and those 13 PET/CT studies were not included in the final comparison, as the result was considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6 normal), the sensitivity and specificity of the PET-O and PET-R were calculated. The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86 for PET-O and PET-R, respectively. The results of the study demonstrated that the accuracy of three-dimensional brain F-18 FDG PET images was significantly improved by Fourier-wavelet restoration filtering. PMID:26420987

  2. A Novel Method for Direct site-specific Radiolabeling of Peptides Using [18F]FDG

    PubMed Central

    Namavari, Mohammad; Cheng, Zhen; Zhang, Rong; De, Abhijit; Levi, Jelena; Hoerner, Joshua K.; Yaghoubi, Shahriar S.; Syud, Faisal A.; Gambhir, Sanjiv S.

    2009-01-01

    We have used the well-accepted and easily available 2-[18F]Fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) tracer as a prosthetic group for synthesis of 18F-labeled peptides. We herein report the synthesis of [18F]FDG-RGD (18F labeled linear RGD) and [18F]FDG-cyclo(RGDDYK) (18F labeled cyclic RGD) as examples of the use of [18F]FDG. We have successfully prepared [18F]FDG-RGD and [18F]FDG-cyclo(RGDDYK) in 27.5% and 41% radiochemical yields (decay corrected) respectively. The receptor binding affinity study of FDG-cyclo(RGDDYK) for integrin αvβ3 , using αvβ3 positive U87MG cells confirmed a competitive displacement with 125I-echistatin as a radioligand. The IC50 value for FDG-cyclo(RGDDYK) was determined to be 0.67 ± 0.19µM. High contrast small animal PET images with relatively moderate tumor uptake were observed for [18F]FDG-RGD and [18F]FDG-cyclo(RGDDYK) as PET probes in xenografts models expressing αvβ3 integrin. In conclusion, we have successfully used [18F]FDG as a prosthetic group to prepare 18F]FDG-RGD and [18F]FDG-cyclic[RGDDYK] based on a simple one step radiosynthesis. The one step radiosynthesis methodology consists of chemoselective oxime formation between an aminooxy functionalized peptide and [18F]FDG. The results have implications for radiolabeling of other macromolecules and would lead to a very simple strategy for routine pre-clinical and clinical use. PMID:19226160

  3. Evaluation of [18F]-FDG-Based Hybrid Imaging Combinations for Assessment of Bone Marrow Involvement in Lymphoma at Initial Staging

    PubMed Central

    2016-01-01

    The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet. PMID:27723817

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

    PubMed

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

    2017-01-01

    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%).

  5. Predicting Future Morphological Changes of Lesions from Radiotracer Uptake in 18F-FDG-PET Images

    PubMed Central

    Bagci, Ulas; Yao, Jianhua; Miller-Jaster, Kirsten; Chen, Xinjian; Mollura, Daniel J.

    2013-01-01

    We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on 18F-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 18F-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75±1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUVmax (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUVmax. We also found that integrating textural features with SUV measurements

  6. Use of Molecular Imaging to Predict Clinical Outcome in Patients With Rectal Cancer After Preoperative Chemotherapy and Radiation

    SciTech Connect

    Konski, Andre Li Tianyu; Sigurdson, Elin; Cohen, Steven J.; Small, William; Spies, Stewart; Yu, Jian Q.; Wahl, Andrew; Stryker, Steven; Meropol, Neal J.

    2009-05-01

    Purpose: To correlate changes in 2-deoxy-2-[18F]fluoro-D-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer. Methods and Materials: Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival. Results: A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival. Conclusions: A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

  7. Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus).

    PubMed

    Via, Laura E; Weiner, Danielle M; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L; Cai, Ying; Coleman, M Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B; Flynn, Joanne L; Barry, Clifton E

    2013-08-01

    Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.

  8. The diagnostic value of [18F]-FDG-PET/CT in hematopoietic radiation toxicity: a Tibet minipig model

    PubMed Central

    Chen, Chi; Yan, Li-Meng; Guo, Kun-Yuan; Wang, Yu-Jue; Zou, Fei; Gu, Wei-Wang; Tang, Hua; Li, Yan-Ling; Wu, Shao-Jie

    2012-01-01

    This study was undertaken to assess the diagnostic value of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography with computed tomography ([18F]-FDG-PET/CT) in the detection of radiation toxicity in normal bone marrow using Tibet minipigs as a model. Eighteen Tibet minipigs were caged in aseptic rooms and randomly divided into six groups. Five groups (n = 3/group) were irradiated with single doses of 2, 5, 8, 11 and 14 Gy of total body irradiation (TBI) using an 8-MV X-ray linear accelerator. These pigs were evaluated with [18F]-FDG-PET/CT, and their marrow nucleated cells were counted. The data were initially collected at 6, 24 and 72 h after treatment and were then collected on Days 5–60 post-TBI at 5-day intervals. At 24 and 72 h post-TBI, marrow standardized uptake value (SUV) data showed a dose-dependent decrease in the radiation dose range from 2–8 Gy. Upon long-term observation, SUV and marrow nucleated cell number in the 11-Gy and 14-Gy groups showed a continuous and marked reduction throughout the entire time course, while Kaplan–Meier curves of survival showed low survival. In contrast, the SUVs in the 2-, 5- and 8-Gy groups showed early transient increases followed by a decline from approximately 72 h through Days 5–15 and then normalized or maintained low levels through the endpoint; marrow nucleated cell number and survival curves showed approximately the same trend and higher survival, respectively. Our findings suggest that [18F]-FDG-PET/CT may be helpful in quickly assessing the absorbed doses and predicting the prognosis in patients. PMID:22843618

  9. Mitotane effects in a H295R xenograft model of adjuvant treatment of adrenocortical cancer.

    PubMed

    Lindhe, O; Skogseid, B

    2010-09-01

    Adrenocortical cancer is one of the most aggressive endocrine malignancies. Growth through the capsule or accidental release of cancer cells during surgery frequently results in metastatic disease. We investigated the antitumoral effect of 2 adrenocorticolytic compounds, O, P'-DDD and MeSO2-DDE, in the adrenocortical cell line H295R both in vitro and as a xenograft model in vivo. H295R cells were injected s. c. in nude mice. O, P'-DDD, MeSO2-DDE, or oil (control) was administered i. p., either simultaneously with cell injection at day 0 (mimicking adjuvant treatment), or at day 48 (established tumors). Accumulation of PET tracers [ (11)C]methionine (MET), [ (11)C] metomidate (MTO), 2-deoxy-2-[ (18)F]fluoro-d-glucose (FDG), and [ (18)F]-l-tyrosine (FLT) in the aggregates were assessed +/- drug treatment in vitro. Tumor growth was significantly inhibited when O, P'-DDD was given at the same time as injection of tumor cells. No significant growth inhibition was observed after treatment with O, P'-DDD at day 48. A significant reduction in FLT uptake and an increased FDG uptake, compared to control, were observed following treatment with 15 microM O, P'-DDD (p<0.01) in vitro. MeSO2-DDE (15 microM) treatment gave rise to a reduced MET and an increased FLT uptake (p<0.01). Both compounds reduced the uptake of MTO compared to control (p<0.01). Treatment with O, P'-DDD simultaneously to inoculation of H295R cells in mice, imitating release of cells during surgery, gave a markedly better effect than treatment of established H295R tumors. We suggest that FLT may be a potential PET biomarker when assessing adrenocortical cancer treatment with O,P'-DDD. Further studies in humans are needed to investigate this.

  10. Preclinical evaluation of the anti-tumor effects of the natural isoflavone genistein in two xenograft mouse models monitored by [18F]FDG, [18F]FLT, and [64Cu]NODAGA-cetuximab small animal PET

    PubMed Central

    Honndorf, Valerie S.; Wiehr, Stefan; Rolle, Anna-Maria; Schmitt, Julia; Kreft, Luisa; Quintanilla-Martinez, Letitia; Kohlhofer, Ursula; Reischl, Gerald; Maurer, Andreas; Boldt, Karsten; Schwarz, Michael; Schmidt, Holger; Pichler, Bernd J.

    2016-01-01

    The natural phytoestrogen genistein is known as protein kinase inhibitor and tumor suppressor in various types of cancers. We studied its antitumor effect in two different xenograft models using positron emission tomography (PET) in vivo combined with ex vivo histology and nuclear magnetic resonance (NMR) metabolic fingerprinting. Procedures A431 and Colo205 tumor-bearing mice were treated with vehicle or genistein (500 mg/kg/d) over a period of 12 days. Imaging was performed with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 3′-deoxy-3′-[18F]fluorothymidine ([18F] FLT). In a second study A431 tumor-bearing mice were treated with vehicle, genistein (500 mg/kg/d), cetuximab (1mg/3d) or a combination of the compounds and imaged using [18F]FDG, [18F]FLT and [64Cu]NODAGA-cetuximab. Data were compared to histology and principal components analysis (PCA) of NMR fingerprinting data. Results Genistein reduced tumor growth significantly in both xenografts. [18F] FLT uptake was consistent in both models and corresponded to histological findings and also PCA whereas [18F]FDG and [64Cu]NODAGA-cetuximab were not suitable for therapy monitoring. Conclusions As mono-therapy the natural isoflavone genistein has a powerful therapeutic effect in vivo on A431 and Colo205 tumors. [18F]FLT has superior consistency compared to the other tested tracers in therapy monitoring, while the treatment effect could be shown on the molecular level by histology and metabolic fingerprinting. PMID:27070087

  11. Small animal simultaneous PET/MRI: initial experiences in a 9.4 T microMRI

    NASA Astrophysics Data System (ADS)

    Harsha Maramraju, Sri; Smith, S. David; Junnarkar, Sachin S.; Schulz, Daniela; Stoll, Sean; Ravindranath, Bosky; Purschke, Martin L.; Rescia, Sergio; Southekal, Sudeepti; Pratte, Jean-François; Vaska, Paul; Woody, Craig L.; Schlyer, David J.

    2011-04-01

    We developed a non-magnetic positron-emission tomography (PET) device based on the rat conscious animal PET that operates in a small-animal magnetic resonance imaging (MRI) scanner, thereby enabling us to carry out simultaneous PET/MRI studies. The PET detector comprises 12 detector blocks, each being a 4 × 8 array of lutetium oxyorthosilicate crystals (2.22 × 2.22 × 5 mm3) coupled to a matching non-magnetic avalanche photodiode array. The detector blocks, housed in a plastic case, form a 38 mm inner diameter ring with an 18 mm axial extent. Custom-built MRI coils fit inside the positron-emission tomography (PET) device, operating in transceiver mode. The PET insert is integrated with a Bruker 9.4 T 210 mm clear-bore diameter MRI scanner. We acquired simultaneous PET/MR images of phantoms, of in vivo rat brain, and of cardiac-gated mouse heart using [11C]raclopride and 2-deoxy-2-[18F]fluoro-d-glucose PET radiotracers. There was minor interference between the PET electronics and the MRI during simultaneous operation, and small effects on the signal-to-noise ratio in the MR images in the presence of the PET, but no noticeable visual artifacts. Gradient echo and high-duty-cycle spin echo radio frequency (RF) pulses resulted in a 7% and a 28% loss in PET counts, respectively, due to high PET counts during the RF pulses that had to be gated out. The calibration of the activity concentration of PET data during MR pulsing is reproducible within less than 6%. Our initial results demonstrate the feasibility of performing simultaneous PET and MRI studies in adult rats and mice using the same PET insert in a small-bore 9.4 T MRI.

  12. Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake

    PubMed Central

    Kumar, Rahul; Mickael, Claudia; Sanders, Linda; Gebreab, Liya; Huber, Kendra M.; Perez, Mario; Smith-Jones, Peter; Serkova, Natalie J.; Tuder, Rubin M.

    2015-01-01

    In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2), followed by an additional 4 wk of normoxia (SU-Hx group). Control rats were treated with carboxymethylcellulose vehicle and 7 wk of normoxia (CMC-Nx group). The rodents then underwent positron emission tomography with sequential administration of two radiotracers, 2-deoxy-2-[18F]fluoroglucose (18F-FDG) and 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18F-FTHA), analogs of glucose and fatty acid, respectively. Five CMC-Nx and 3 SU-Hx rats completed the entire experimental protocol. In the RV, there was a mild increase in 18F-FDG uptake (1.35-fold, P = 0.085) and a significant decrease in 18F-FTHA uptake (−2.1-fold, P < 0.05) in the SU-Hx rats relative to the CMC-Nx rats. In the LV, SU-Hx rats had less uptake of both radiotracers compared with CMC-Nx rats. Less RV fatty acid uptake in SPH was corroborated by decreased fatty acid transporters and enzymes in the RV tissue, and specifically a decrease in lipoprotein lipase. In the RV in rats with SPH, there is a major shift in metabolic substrate preference, largely due to decreased fatty acid uptake. PMID:26115672

  13. Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography

    NASA Astrophysics Data System (ADS)

    Sheth, Rahul A.; Josephson, Lee; Mahmood, Umar

    2009-11-01

    A fluorescent analog to 2-deoxy-2 [18F] fluoro-D-glucose position emission tomography (FDG-PET) would allow for the introduction of metabolic imaging into intraoperative and minimally invasive settings. We present through in vitro and in vivo experimentation an evaluation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescently labeled glucose molecule, as a molecular beacon of glucose utilization. The competitive inhibition of 2-NBDG uptake by excess free glucose is directly compared against FDG uptake inhibition in cultured cells. 2-NBDG uptake in the brain of a mouse experiencing a generalized seizure is measured, as well as in subcutaneously implanted tumors in mice during fed and fasting states. Localization of 2-NBDG into malignant tissues is studied by laser scanning microscopy. The clinical relevance of 2-NBDG imaging is examined by performing fluorescence colonoscopy, and by correlating preoperative FDG-PET with intraoperative fluorescence imaging. 2-NBDG exhibits a similar uptake inhibition to FDG by excess glucose in the growth media. Uptake is significantly increased in the brain of an animal experiencing seizures versus control, and in subcutaneous tumors after the animals are kept nil per os (NPO) for 24 h versus ad libidum feeding. The clinical utility of 2-NBDG is confirmed by the demonstration of very high target-to-background ratios in minimally invasive and intraoperative imaging of malignant lesions. We present an optical analog of FDG-PET to extend the applicability of metabolic imaging to minimally invasive and intraoperative settings.

  14. Correlation of 18F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

    PubMed Central

    Shusharina, Nadya; Cho, Joseph; Sharp, Gregory C.; Choi, Noah C.

    2014-01-01

    Purpose To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (18F-FDG PET) before and after therapy in recurrent lung cancer. Methods and Materials We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial 18F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUVmax) (≥50% of SUVmax) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUVmax. The VOI of pretherapy and posttherapy 18F-FDG PET images were correlated for the extent of overlap. Results The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. Conclusions VOI defined by the SUVmax- ≥50% isocontour may be a biological target volume for escalated radiation dose. PMID:24725696

  15. Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

    PubMed Central

    Kunos, Charles A.; Fabien, Jeffrey M.; Shanahan, John P.; Collen, Christine; Gevaert, Thierry; Poels, Kenneth; Van den Begin, Robbe; Engels, Benedikt; De Ridder, Mark

    2015-01-01

    Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-ᴅ-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors. PMID:26131774

  16. Models for in vivo kinetic interactions of dopamine D2-neuroreceptors and 3-(2'-( sup 18 F)fluoroethyl)spiperone examined with positron emission tomography

    SciTech Connect

    Bahn, M.M.; Huang, S.C.; Hawkins, R.A.; Satyamurthy, N.; Hoffman, J.M.; Barrio, J.R.; Mazziotta, J.C.; Phelps, M.E. )

    1989-12-01

    The in vivo tracer kinetics of 3-(2'-(18F)fluoroethyl)spiperone (FESP) in the caudate/striatum and cerebellar regions of the human and monkey brain were studied with positron emission tomography (PET). The minimal model configuration that can describe the kinetics was determined statistically. Three two-compartment model configurations were found to be suitable for describing the kinetics in caudate/striatum and cerebellum: (1) a nonlinear model (five parameters) applicable to studies using nontracer (partially saturating) quantities of FESP in monkey striatum, (2) a linear four-parameter model applicable to the caudate/striatal and cerebellar kinetics in human and monkey studies with tracer quantities of FESP, and (3) a linear three-parameter model derived from the four-parameter model by assuming irreversible binding applicable to tracer studies of the human caudate. In the human studies, when the caudate kinetics (n = 4) were fit by model 2 (with four parameters), the value of the in vivo ligand dissociation constant kd was found to be 0.0015 +/- 0.0032/min. The three-parameter model (model 3) was found to fit the data equally well: this model is equivalent to model 2 with kd set to zero. In the monkey studies, it was found that for short (90 min) studies using tracer quantities of FESP, model 2 fit the striatal kinetics better than model 3. The parameters estimated using model 2 (four parameters) were in better agreement with those estimated by the nonlinear model (model 1) than those estimated using model 3 (three parameters). The use of a graphical approach gives estimates of the plasma-tissue fractional transport rate constant K1 and the net uptake constant K3 comparable to estimates using model 3 for both human and monkey studies.

  17. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

    PubMed

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson's disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.

  18. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study

    PubMed Central

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  19. A Prospective Analysis of Positron Emission Tomography and Conventional Imaging for Detection of Stage IV Metastatic Melanoma in Patients Undergoing Metastasectomy

    PubMed Central

    Finkelstein, Steven E.; Carrasquillo, Jorge A.; Hoffman, John M.; Galen, Barbara; Choyke, Peter; White, Donald E.; Rosenberg, Steven A.; Sherry, Richard M.

    2008-01-01

    Background Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy. Methods This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations. Results Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively. Conclusions Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis. PMID:15249335

  20. Differences in response to food stimuli in a rat model of obesity: in-vivo assessment of brain glucose metabolism

    PubMed Central

    Thanos, PK; Michaelides, M; Gispert, J-D; Pascau, J; Soto-Montenegro, ML; Desco, M; Wang, R; Wang, G-J; Volkow, ND

    2009-01-01

    Objective Food intake is regulated by factors that modulate caloric requirements as well as food’s reinforcing properties. In this study, we measured brain glucose utilization to an olfactory stimulus (bacon scent), and we examined the role of food restriction and genetic predisposition to obesity on such brain metabolic activity. Methods Zucker obese (Ob) and lean (Le) rats were divided into four groups: (1) Ob ad-libitum fed, (2) Ob food restricted (70% of ad libitum), (3) Le ad-libitum fed and (4) Le food restricted. Rats were scanned using µ-positron emission tomography and 2-[18F]-fluoro-2-deoxy-d-glucose under two conditions: (1) baseline scan (no stimulation) and (2) challenge scan (food stimulation, FS). Results FS resulted in deactivation of the right and left hippocampus. Ob rats showed greater changes with FS than Le rats (deactivation of hippocampus and activation of the medial thalamus) and Ob but not Le animals deactivated the frontal cortex and activated the superior colliculus. Access to food resulted in an opposite pattern of metabolic changes to the food stimuli in olfactory nucleus (deactivated in unrestricted and activated in restricted) and in right insular/parietal cortex (activated in unrestricted and deactivated in restricted). In addition, restricted but not unrestricted animals activated the medial thalamus. Conclusions The greater changes in the Ob rats suggest that leptin modulates the regional brain responses to a familiar food stimulus. Similarly, the differences in the pattern of responses with food restriction suggest that FS is influenced by access to food conditions. The main changes with FS occurred in the hippocampus, a region involved in memory, the insular cortex, a region involved with interoception (perception of internal sensations), the medial thalamus (region involved in alertness) and in regions involved with sensory perception (olfactory bulb, olfactory nucleus, occipital cortex, superior colliculus and parietal

  1. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

    SciTech Connect

    Volkow, N.D.; Fowler, J.; Wang, G.J.; Telang, F.; Logan, J.; Jayne, M.; Ma, Y.; Pradhan, K.; Wong, C.T.; Swanson, J.M.

    2010-01-01

    Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statistical parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.

  2. Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

    SciTech Connect

    Liao, C.-T.; Chang, Joseph T.-C.; Wang, H.-M.; Ng, S.-H.; Hsueh, C.; Lee, L.-Y.; Lin, C.-H.; Chen, I.-H.; Huang, S.-F.

    2009-03-01

    Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-D-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for {>=}24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth {>=}12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of {>=}19.3 and tumor depth of {>=}12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. Conclusion: The combination of the primary tumor SUVmax ({>=}19.3) and pathologic tumor depth ({>=}12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death.

  3. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

    PubMed

    Jeong, Jeong-Won; Asano, Eishi; Kumar Pilli, Vinod; Nakai, Yasuo; Chugani, Harry T; Juhász, Csaba

    2017-03-21

    To determine the spatial relationship between 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp, 2017. © 2017

  4. Comparability of [(18)F]THK5317 and [(11)C]PIB blood flow proxy images with [(18)F]FDG positron emission tomography in Alzheimer's disease.

    PubMed

    Rodriguez-Vieitez, Elena; Leuzy, Antoine; Chiotis, Konstantinos; Saint-Aubert, Laure; Wall, Anders; Nordberg, Agneta

    2017-02-01

    For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer's disease and nine Alzheimer's disease dementia patients underwent [(18)F]THK5317, carbon-11 Pittsburgh Compound-B ([(11)C]PIB), and 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography to assess the possible use of early-phase [(18)F]THK5317 and R1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [(18)F]THK5317 (early-phase SUVr and R1) was compared with that of [(11)C]PIB (early-phase SUVr and R1) and [(18)F]FDG. Strong positive correlations were found between [(18)F]THK5317 (early-phase, R1) and [(18)F]FDG, particularly in frontal and temporoparietal regions. Differences in correlations between early-phase and R1 ([(18)F]THK5317 and [(11)C]PIB) and [(18)F]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [(18)F]THK5317 and R1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [(18)F]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer's disease, with potential clinical applications.

  5. Cellular distribution of Glut-1 and Glut-5 in benign and malignant human prostate tissue.

    PubMed

    Reinicke, Karin; Sotomayor, Paula; Cisterna, Pedro; Delgado, Carolina; Nualart, Francisco; Godoy, Alejandro

    2012-02-01

    Over-expression of hexose transporters (Gluts), specifically Glut-1, is a common event in human malignancies. In prostate cancer (CaP), however, expression of Gluts has been characterized poorly. In this study, expression and distribution of Glut-1 and Glut-5 proteins were characterized using immunohistochemistry in 76 specimens of benign prostate, 10 specimens of high-grade intraepithelial neoplasia (HGPIN), and 28 specimens of CaP. In addition, mRNA expression of Glut-2, Glut-7, Glut-9, and Glut-11 was analyzed in a set of five specimens of benign prostate and CaP. In benign prostate, Glut-1 localized to the basal cells and to the basolateral membrane of secretory/luminal epithelial cells. Glut-5, however, localized to the apical membrane of secretory/luminal epithelial cells. In HGPIN, Glut-1 was immunohistochemically undetectable. Glut-5, however, localized to the apical membrane of the neoplastic epithelial cells. In CaP, Glut-1 and Glut-5, were immunohistochemically undetectable. However, over-expression of GLUT1 was observed in some specimens of highly proliferative intraductal CaP. Glut-7, Glut-9, and Glut-11 mRNAs were detected in benign prostate and CaP, however, only Glut-11 mRNA was consistently up-regulated in CaP compared to benign prostate. Low levels of expression of Glut-1 protein in the majority of CaP could explain, at least in part, the limited clinical applicability of positron emission tomography using 2-[18F]-fluoro-2-deoxy-D-glucose for imaging CaP. Moreover, expression of Glut-5 in HGPIN suggested that fructose could be utilized as potential metabolic substrate in HGPIN. Understanding the molecular mechanisms involved in regulation/dysregulation of Gluts in CaP could provide insight in the understanding of hexose metabolism in CaP.

  6. Non-invasive evaluation of neuroprotective drug candidates for cerebral infarction by PET imaging of mitochondrial complex-I activity

    NASA Astrophysics Data System (ADS)

    Fukuta, Tatsuya; Asai, Tomohiro; Ishii, Takayuki; Koide, Hiroyuki; Kiyokawa, Chiaki; Hashimoto, Masahiro; Kikuchi, Takashi; Shimizu, Kosuke; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2016-07-01

    The development of a diagnostic technology that can accurately determine the pathological progression of ischemic stroke and evaluate the therapeutic effects of cerebroprotective agents has been desired. We previously developed a novel PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) for detecting activity of mitochondrial complex I (MC-I). This probe was shown to visualize neuronal damage in the living brain of rodent and primate models of neurodegenerative diseases. In the present study, [18F]BCPP-EF was applied to evaluate the therapeutic effects of a neuroprotectant, liposomal FK506 (FK506-liposomes), on cerebral ischemia/reperfusion (I/R) injury in transient middle cerebral artery occlusion rats. The PET imaging using [18F]BCPP-EF showed a prominent reduction in the MC-I activity in the ischemic brain hemisphere. Treatment with FK506-liposomes remarkably increased the uptake of [18F]BCPP-EF in the ischemic side corresponding to the improvement of blood flow disorders and motor function deficits throughout the 7 days after I/R. Additionally, the PET scan could diagnose the extent of the brain damage accurately and showed the neuroprotective effect of FK506-liposomes at Day 7, at which 2, 3, 5-triphenyltetrazolium chloride staining couldn’t visualize them. Our study demonstrated that the PET technology using [18F]BCPP-EF has a potent capacity to evaluate the therapeutic effect of drug candidates in living brain.

  7. Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

    PubMed Central

    Shin, Eun Sil; Hwang, Onyou; Hwang, Yu-Shik; Suh, Jun-Kyo Francis; Chun, Young Il

    2014-01-01

    Objective Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[18F]-fluoro-D-glucose ([18F]-FDG) and [18F]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([18F]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [18F]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human β2 microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine. PMID:25535514

  8. Subacute administration of fluoxetine prevents short-term brain hypometabolism and reduces brain damage markers induced by the lithium-pilocarpine model of epilepsy in rats.

    PubMed

    Shiha, Ahmed Anis; de Cristóbal, Javier; Delgado, Mercedes; Fernández de la Rosa, Rubén; Bascuñana, Pablo; Pozo, Miguel A; García-García, Luis

    2015-02-01

    The role of serotonin (5-hydroxytryptamine; 5-HT) in epileptogenesis still remains controversial. In this regard, it has been reported that serotonergic drugs can alter epileptogenesis in opposite ways. The main objective of this work was to investigate the effect of the selective 5-HT selective reuptake inhibitor (SSRI) fluoxetine administered subacutely (10mg/kg/day×7 days) on the eventual metabolic impairment induced by the lithium-pilocarpine model of epilepsy in rats. In vivo 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F] FDG) positron emission tomography (PET) was performed to assess the brain glucose metabolic activity on days 3 and 30 after the insult. In addition, at the end of the experiment (day 33), several histochemical and neurochemical assessments were performed for checking the neuronal functioning and integrity. Three days after the insult, a marked reduction of [(18)F] FDG uptake (about 30% according to the brain region) was found in all brain areas studied. When evaluated on day 30, although a hypometabolism tendency was observed, no statistically significant reduction was present in any region analyzed. In addition, lithium-pilocarpine administration was associated with medium-term hippocampal and cortical damage, since it induced neurodegeneration, glial activation and augmented caspase-9 expression. Regarding the effect of fluoxetine, subacute treatment with this SSRI did not significantly reduce the mortality rate observed after pilocarpine-induced seizures. However, fluoxetine did prevent not only the short-term metabolic impairment, but also the aforementioned signs of neuronal damage in surviving animals to lithium-pilocarpine protocol. Finally, fluoxetine increased the density of GABAA receptor both at the level of the dentate gyrus and CA1-CA2 regions in pilocarpine-treated animals. Overall, our data suggest a protective role for fluoxetine against pilocarpine-induced brain damage. Moreover, this action may be associated with an increase of

  9. Preclinical Properties of 18F-AV-45: A PET Agent for Aβ Plaques in the Brain

    PubMed Central

    Choi, Seok Rye; Golding, Geoff; Zhuang, Zhiping; Zhang, Wei; Lim, Nathaniel; Hefti, Franz; Benedum, Tyler E.; Kilbourn, Michael R.; Skovronsky, Daniel; Kung, Hank F.

    2011-01-01

    β-amyloid plaques (Aβ plaques) in the brain, containing predominantly fibrillary Aβ peptide aggregates, represent a defining pathologic feature of Alzheimer disease (AD). Imaging agents targeting the Aβ plaques in the living human brain are potentially valuable as biomarkers of pathogenesis processes in AD. (E)-4-(2-(6-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine (18F-AV-45) is such as an agent currently in phase III clinical studies for PET of Aβ plaques in the brain. Methods In vitro binding of 18F-AV-45 to Aβ plaques in the postmortem AD brain tissue was evaluated by in vitro binding assay and autoradiography. In vivo biodistribution of 18F-AV-45 in mice and ex vivo autoradiography of AD transgenic mice (APPswe/PSEN1) with Aβ aggregates in the brain were performed. Small-animal PET of a monkey brain after an intravenous injection of 18F-AV-45 was evaluated. Results 18F-AV-45 displayed a high binding affinity and specificity to Aβ plaques (Kd, 3.72 ± 0.30 nM). In vitro autoradiography of postmortem human brain sections showed substantial plaque labeling in AD brains and not in the control brains. Initial high brain uptake and rapid washout from the brain of healthy mice and monkey were observed. Metabolites produced in the blood of healthy mice after an intravenous injection were identified. 18F-AV-45 displayed excellent binding affinity to Aβ plaques in the AD brain by ex vivo autoradiography in transgenic AD model mice. The results lend support that 18F-AV-45 may be a useful PET agent for detecting Aβ plaques in the living human brain. PMID:19837759

  10. Vacuum ultraviolet photon-mediated production of [(18) F]F2.

    PubMed

    Krzyczmonik, Anna; Keller, Thomas; Kirjavainen, Anna K; Forsback, Sarita; Solin, Olof

    2017-04-01

    The chemistry of F2 and its derivatives are amenable to facile aliphatic or aromatic substitution, as well as electrophilic addition. The main limitation in the use of [(18) F]F2 for radiopharmaceutical synthesis is the low specific activity achieved by the traditional methods of production. The highest specific activities, 55 GBq/μmol, for [(18) F]F2 have been achieved so far by using electrical discharge in the post-target production of [(18) F]F2 gas from [(18) F]CH3 F. We demonstrate that [(18) F]F2 is produced by illuminating a gas mixture of neon/F2 /[(18) F]CH3 F with vacuum ultraviolet photons generated by an excimer laser. We tested several illumination chambers and production conditions. The effects of the initial amount of [(18) F]F(-) , amount of carrier F2 , and number of 193-nm laser pulses at constant power were evaluated regarding radiochemical yield and specific activity. The specific activity attained for [(18) F]F2 -derived [(18) F]NFSi was 10.3 ± 0.9 GBq/μmol, and the average radiochemical yield over a wide range of conditions was 6.7% from [(18) F]F(-) . The production can be improved by optimization of the synthesis device and procedures. The use of a commercially available excimer laser and the simplicity of the process can make this method relatively easy for adaptation in radiochemistry laboratories.

  11. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background.

    PubMed

    Davies, Barry R; Greenwood, Hannah; Dudley, Phillippa; Crafter, Claire; Yu, De-Hua; Zhang, Jingchuan; Li, Jing; Gao, Beirong; Ji, Qunsheng; Maynard, Juliana; Ricketts, Sally-Ann; Cross, Darren; Cosulich, Sabina; Chresta, Christine C; Page, Ken; Yates, James; Lane, Clare; Watson, Rebecca; Luke, Richard; Ogilvie, Donald; Pass, Martin

    2012-04-01

    AKT is a key node in the most frequently deregulated signaling network in human cancer. AZD5363, a novel pyrrolopyrimidine-derived compound, inhibited all AKT isoforms with a potency of 10 nmol/L or less and inhibited phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μmol/L. AZD5363 monotherapy inhibited the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of 3 μmol/L or less. Cell lines derived from breast cancers showed the highest frequency of sensitivity. There was a significant relationship between the presence of PIK3CA and/or PTEN mutations and sensitivity to AZD5363 and between RAS mutations and resistance. Oral dosing of AZD5363 to nude mice caused dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts (PRAS40 phosphorylation EC(50) ~ 0.1 μmol/L total plasma exposure), reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 caused dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2(+) breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhanced the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. It is concluded that AZD5363 is a potent inhibitor of AKT with pharmacodynamic activity in vivo, has potential to treat a range of solid and hematologic tumors as monotherapy or a combinatorial agent, and has potential for personalized medicine based on the genetic status of PIK3CA, PTEN, and RAS. AZD5363 is currently in phase I clinical trials.

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

    PubMed

    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-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-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 (18)F-FDG and/or (18)F-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 (18)F-FDG and (18)F-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 (18)F-FDG and/or (18)F-FLT PET for response monitoring of cancer therapeutics.

  13. Metabolic Response of Prostate Cancer to Nicotinamide Phophoribosyltransferase Inhibition in a Hyperpolarized MR/PET Compatible Bioreactor

    PubMed Central

    Keshari, Kayvan R.; Wilson, David M.; Van Criekinge, Mark; Sriram, Renuka; Koelsch, Bertram L.; Wang, Zhen J.; VanBrocklin, Henry F.; Peehl, Donna M.; O’Brien, Tom; Sampath, Deepak; Carano, Richard A. D.; Kurhanewicz, John

    2015-01-01

    Background Metabolic shifts in disease are of great interest for the development of novel therapeutics. In cancer treatment, these therapies exploit the metabolic phenotype associated with oncogenesis and cancer progression. One recent strategy involves the depletion of the cofactors needed to maintain the high rate of glycolysis seen with the Warburg effect. Specifically, blocking nicotinamide adenine dinucleotide (NAD) biosynthesis via nicotinamide phosphoribosyltransferase (NAMPT) inhibition depletes cancer cells of the NAD needed for glycolysis. To characterize this metabolic phenotype in vivo and describe changes in flux with treatment, non-invasive biomarkers are necessary. One such biomarker is hyperpolarized (HP) [1-13C] pyruvate, a clinically translatable probe that allows real-time assessment of metabolism. Methods We therefore developed a cell perfusion system compatible with HP magnetic resonance (MR) and positron emission tomography (PET) to develop translatable biomarkers of response to NAMPT inhibition in reduced volume cell cultures. Results Using this platform, we observed a reduction in pyruvate flux through lactate dehydrogenase with NAMPT inhibition in prostate cancer cells, and showed that both HP lactate and 2-[18F] fluoro-2-deoxy-D-glucose (FDG) can be used as biomarkers for treatment response of such targeted agents. Moreover, we observed dynamic flux changes whereby HP pyruvate was re-routed to alanine, providing both positive and negative indicators of treatment response. Conclusions This study demonstrated the feasibility of a MR/PET compatible bioreactor approach to efficiently explore cell and tissue metabolism, the understanding of which is critical for developing clinically translatable biomarkers of disease states and responses to therapeutics. PMID:26177608

  14. Metabolite identification of a radiotracer by electrochemistry coupled to liquid chromatography with mass spectrometric and radioactivity detection.

    PubMed

    Baumann, Anne; Faust, Andreas; Law, Marylin P; Kuhlmann, Michael T; Kopka, Klaus; Schäfers, Michael; Karst, Uwe

    2011-07-01

    Radioligands, which specifically bind to a receptor or enzyme (target), enable molecular imaging of the target expression by positron emission tomography (PET). One very promising PET tracer is (S)-1-(4-(2-[(18)F]-fluoroethoxy)benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin (isatin), a caspase-3 inhibitor, which has been developed at the University Hospital of Münster to image cell death (apoptosis). The translation of this novel tracer from preclinical evaluation to clinical examinations requires biodistribution studies, which characterize the pharmakodynamics and metabolic fate of the compound. This information is used to further optimize the radioligands and to interpret radioactive signals from tissues upon injection of the radioligand in vivo with respect to their specificity. The analysis of the metabolism of radioligands is hampered by the low amount of the compound being typically injected (nano/picomolar amount per injection). In the present study, electrochemistry (EC) is applied to elucidate the oxidative metabolism pathway of the radiotracer. Previous studies have demonstrated that EC can be utilized as a complementary tool to conventional in vitro approaches in drug metabolism studies. Thereby, potential oxidative metabolites of the isatin are determined by EC coupled to electrospray ionization mass spectrometry (EC/ESI-MS). Moreover, using EC/liquid chromatography (LC) and ESI-ion trap MS(n), structural elucidation of the oxidation products is performed. Comparatively to EC, in vitro metabolism studies with rat liver microsomes are conducted. Finally, the developed LC/ESI-MS method is applied to determine metabolites in body fluids and cell extracts from in vivo studies with the nonradioactive ((19)F) and radioactive isatin ((18)F). On the basis of the electrochemically generated oxidation products of the radioligand, the major radioactive metabolite occurring in vivo was successfully identified.

  15. 3-(2'-( sup 18 F)fluoroethyl)spiperone: In vivo biochemical and kinetic characterization in rodents, nonhuman primates, and humans

    SciTech Connect

    Barrio, J.R.; Satyamurthy, N.; Huang, S.C.; Keen, R.E.; Nissenson, C.H.; Hoffman, J.M.; Ackermann, R.F.; Bahn, M.M.; Mazziotta, J.C.; Phelps, M.E. )

    1989-12-01

    3-(2'-(18F)fluoroethyl)spiperone (FESP), a recently developed dopamine D2-receptor binding radiopharmaceutical, was used for dynamic characterization of dopamine-receptor binding in Macaca nemestrina monkeys and humans with positron emission tomography (PET). FESP in vitro binding properties to the dopamine receptor (IC50 = 1.5 nM) are similar to those of spiperone. Serial PET scans in monkeys after intravenous bolus injection of FESP revealed specific radioactivity accumulation in striatum (rich in dopamine D2-receptors), whereas radioactivity concentration declined after 20 min in frontal cortex (serotonin receptors) and more rapidly in cerebellum (nonspecific binding). Specific dopamine D2-receptor binding was saturated with increasing concentrations of radioligand (specific activity range: 1-10,000 Ci/mmol), was stereospecifically blocked with (+)butaclamol (0.5 mg/kg), and showed only partial displacement with spiperone (200 micrograms/kg, i.v. administration 90 min after FESP injection). From PET experiments with FESP in humans, it is possible to visualize accumulation of radioactivity in striatum in a manner similar to that observed in monkeys and, ex vivo, in rodents (adult male Sprague-Dawley rats). Biochemical analyses in rat brain revealed that the activity (approximately 90%) in striatum was unmodified FESP up to 4 h after injection. On the other hand, FESP was metabolized peripherally (rat greater than monkey greater than human), with only 11% of plasma radioactivity remaining as intact FESP in rodents and 54% in humans after 2 h. Based on these interspecies scaling pharmacokinetic data, it is unequivocal that FESP peripheral metabolites do not significantly contribute to the accumulated radioactivity in striatal tissue. Therefore, it is concluded that FESP is suitable for the quantitative estimation of dopamine D2-receptor sites using PET.

  16. Synthesis and preliminary biological evaluation of S-11C-methyl-D-cysteine as a new amino acid PET tracer for cancer imaging.

    PubMed

    Huang, Tingting; Tang, Ganghua; Wang, Hongliang; Nie, Dahong; Tang, Xiaolan; Liang, Xiang; Hu, Kongzhen; Yi, Chang; Yao, Baoguo; Tang, Caihua

    2015-04-01

    S-(11)C-methyl-L-cysteine (LMCYS) is an attractive amino acid tracer for clinical tumor positron emission tomography (PET) imaging. D-isomers of some radiolabeled amino acids are potential PET tracers for tumor imaging. In this work, S-(11)C-methyl-D-cysteine (DMCYS), a D-amino acid isomer of S-(11)C-methyl-cysteine for tumor imaging was developed and evaluated. DMCYS was prepared by (11)C-methylation of the precursor D-cysteine, with an uncorrected radiochemical yield over 50 % from (11)CH3I within a total synthesis time from (11)CO2 about 12 min. In vitro competitive inhibition studies showed that DMCYS uptake was primarily transported through the Na(+)-independent system L, and also the Na(+)-dependent system B(0,+) and system ASC, with almost no system A. In vitro incorporation experiments indicated that almost no protein incorporation was found in Hepa 1-6 hepatoma cell lines. Biodistribution studies demonstrated higher uptake of DMCYS in pancreas and liver at 5 min post-injection, relatively lower uptake in brain and muscle, and faster radioactivity clearance from most tissues than those of L-isomer during the entire observation time. In the PET imaging of S180 fibrosarcoma-bearing mice and turpentine-induced inflammatory model mice, 2-(18)F-fluoro-2-deoxy-D-glucose (FDG) exhibited significantly high accumulation in both tumor and inflammatory lesion with low tumor-to-inflammation ratio of 1.40, and LMCYS showed low tumor-to-inflammation ratio of 1.64 at 60 min post-injection. By contrast, DMCYS showed moderate accumulation in tumor and very low uptake in inflammatory lesion, leading to relatively higher tumor-to-inflammation ratio of 2.25 than (11)C-methyl-L-methionine (MET) (1.85) at 60 min post-injection. Also, PET images of orthotopic transplanted glioma models demonstrated that low uptake of DMCYS in normal brain tissue and high uptake in brain glioma tissue were observed. The results suggest that DMCYS is a little better than the corresponding L

  17. Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation

    PubMed Central

    2011-01-01

    Background Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of β3-adrenergic receptor-mediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective β3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT]. Methods Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation. Results CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5, and 1 mg/kg CL, respectively. Ex vivo 18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET. Conclusion Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism. PMID:22214183

  18. Dissecting molecular mechanisms in the living brain of dementia patients.

    PubMed

    Barrio, Jorge R; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Petric, Andrej; Small, Gary W; Kepe, Vladimir

    2009-07-21

    Understanding the molecular mechanisms associated with the development of dementia is essential for designing successful interventions. Dementia, like cancer and cardiovascular disease, requires early detection to potentially arrest or prevent further disease progression. By the time a neurologist begins to manage clinical symptoms, the disease has often damaged the brain significantly. Because successful treatment is the logical goal, detecting the disease when brain damage is still limited is of the essence. The role of chemistry in this discovery process is critical. With the advent of molecular imaging, the understanding of molecular mechanisms in human neurodegenerative diseases has exploded. Traditionally, knowledge of enzyme and neurotransmitter function in humans has been extrapolated from animal studies, but now we can acquire data directly from both healthy and diseased human subjects. In this Account, we describe the use of molecular imaging probes to elucidate the biochemical and cellular bases of dementia (e.g., Alzheimer's disease) and the application of these discoveries to the design of successful therapeutic interventions. Molecular imaging permits observation and evaluation of the basic molecular mechanisms of disease progression in the living brains of patients. 2-Deoxy-2-[(18)F]fluoro-d-glucose is used to assess the effect of Alzheimer's disease progression on neuronal circuits projecting from and to the temporal lobe (one of the earliest metabolic signs of the disease). Recently, we have developed imaging probes for detection of amyloid neuropathology (both tau and beta-amyloid peptide deposits) and neuronal losses. These probes allow us to visualize the development of pathology in the living brain of dementia patients and its consequences, such as losses of critical neurons associated with memory deficits and other neuropsychiatric impairments. Because inflammatory processes are tightly connected to the brain degenerative processes

  19. Dosimetric evaluation of the staff working in a PET/CT department

    NASA Astrophysics Data System (ADS)

    Dalianis, K.; Malamitsi, J.; Gogou, L.; Pagou, M.; Efthimiadou, R.; Andreou, J.; Louizï, A.; Georgiou, E.

    2006-12-01

    The dosimetric literature data concerning the medical personnel working in positron emission tomography/computed tomography (PET/CT) departments are limited. Therefore, we measured the radiation dose of the staff working in the first PET/CT department in Greece at the Diagnostic and Therapeutic Center of Athens HYGEIA—Harvard Medical International. As, for the time being, only 2-deoxy-2-[ 18F]fluoro-d-glucose (FDG) PET studies are performed, radiation dose measurements concern those derived from dispensing of the radiopharmaceutical as well as from the patients undergoing FDG-PET imaging. Our aim is to develop more effective protective measures against radionuclide exposure. To estimate the effective dose from external exposure, all seven members of the staff (two nurses, two medical physicists, two technologists, one secretary) had TLD badges worn at the upper pocket of their overall, TLD rings on the right hand and digital dosimeters at their upper side pocket. In addition, isodose curves were measured with thermoluminescence detectors for distances of 20, 50, 70 and 100 cm away from patients who had been injected with 18F-FDG. Dose values of the PET/CT staff were measured with digital detectors, TLD badges and TLD rings over the first 8 months for a total of 160 working days of the department's operation, consisting of a workload of about 10-15 patients/week who received 250-420 MBq of 18F-FDG each. Whole - body collective doses and hand doses for the staff were the following: Nurse #1 received 1.6 mSv as a whole body dose and 2,1 as a hand dose, Nurse #2 received 1.9 and 2.4 mSv respectively. For medical physicist #1 the dose values were 1.45 mSv whole body and 1.7 mSv hand dose, for medical physicist #2 1.67 mSv wholebody dose and 1.55 mSv hand dose and for technologists #1 & #2 the whole body doses were 0.7 and 0.64 mSv respectively. Lastly, the secretary received 0.1 mSv whole body dose. These preliminary data have shown that the dose levels of our PET

  20. 18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

    PubMed Central

    Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Urup, Thomas; Broholm, Helle; El Ali, Henrik; Poulsen, Hans Skovgaard; Stockhausen, Marie-Thérése

    2015-01-01

    Background Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts. Methods Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours. Results Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUVmax tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours. Conclusion 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future

  1. Monitoring of neoadjuvant chemotherapy using multiparametric, ²³Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer.

    PubMed

    Jacobs, Michael A; Ouwerkerk, Ronald; Wolff, Antonio C; Gabrielson, Edward; Warzecha, Hind; Jeter, Stacie; Bluemke, David A; Wahl, Richard; Stearns, Vered

    2011-07-01

    We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7-8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-D-glucose (¹⁸FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (²³Na) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 ± 11 years) who received PST underwent radiological imaging of ¹⁸FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29-20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, ²³Na MRI, and PET/CT metrics as radiological

  2. Monitoring of neoadjuvant chemotherapy using multiparametric, 23Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer

    PubMed Central

    Ouwerkerk, Ronald; Wolff, Antonio C.; Gabrielson, Edward; Warzecha, Hind; Jeter, Stacie; Bluemke, David A.; Wahl, Richard; Stearns, Vered

    2011-01-01

    We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7–8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (23Na) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 ± 11 years) who received PST underwent radiological imaging of 18FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29–20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, 23Na MRI, and PET/CT metrics as radiological

  3. Influence of Software Tool and Methodological Aspects of Total Metabolic Tumor Volume Calculation on Baseline [18F]FDG PET to Predict Survival in Hodgkin Lymphoma

    PubMed Central

    Kanoun, Salim; Tal, Ilan; Berriolo-Riedinger, Alina; Rossi, Cédric; Riedinger, Jean-Marc; Vrigneaud, Jean-Marc; Legrand, Louis; Humbert, Olivier; Casasnovas, Olivier; Brunotte, François; Cochet, Alexandre

    2015-01-01

    Aim To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL). Methods 59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUVmax (TMTV041) and using a per-patient adapted threshold based on SUVmax of the liver (>125% and >140% of SUVmax of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure. Results Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313ml and 0.70, 432ml and 0.68, 450ml and 0.68, 330ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140. Conclusion In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant

  4. Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences

    PubMed Central

    Fakhri, Georges El; Trott, Cathryn M.; Sitek, Arkadiusz; Bonab, Ali; Alpert, Nathaniel M.

    2013-01-01

    Purpose With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions. Procedures To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (brain metabolism) and 11C-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously. Results The theoretical development shows that GFADS can decompose the studies at several levels: (1) It decomposes the FDG and raclopride study so that they can be analyzed as though they were obtained separately. (2) If additional physiologic/anatomic constraints can be imposed, further decomposition is possible. (3) For the example of raclopride, specific and nonspecific binding can be determined on a pixel-by-pixel basis. We found good agreement between the estimated GFADS factors and the simulated ground truth time activity curves (TACs), and between the GFADS factor images and the corresponding ground truth activity distributions with errors less than 7.3±1.3 %. Biases in estimation of specific D2 binding and relative metabolism activity were within 5.9±3.6 % compared to the ground truth values. We also evaluated our approach in simultaneous dual-isotope brain PET studies in a rhesus monkey and obtained accuracy of better than 6 % in a mid-striatal volume, for striatal activity estimation. Conclusions Dynamic image sequences acquired following near-simultaneous injection of two PET radiopharmaceuticals

  5. Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons

    PubMed Central

    Lim, Keunpoong; Labaree, David; Ropchan, Jim; Harris, Paul; Huang, Yiyun; Ichise, Masanori; Carson, Richard E.; Cline, Gary W.

    2017-01-01

    Introduction 18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(−)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. Methods PET scans were conducted for up to 4 h with (+) and (−) enantiomers. Displacement experiments using unlabeled (+) and (−) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F-FP-(−)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90 min post-injection. Results Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(−)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND. Conclusions VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume

  6. Long-term effects of 'ecstasy' abuse on the human brain studied by FDG PET.

    PubMed

    Buchert, R; Obrocki, J; Thomasius, R; Väterlein, O; Petersen, K; Jenicke, L; Bohuslavizki, K H; Clausen, M

    2001-08-01

    The popular recreational drug, 'ecstasy', mainly contains 3,4-methylenedioxymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of causing neurotoxic lesions to the serotonergic system as demonstrated by animal studies, examinations of human cerebrospinal fluid, and the first positron emission tomography (PET) studies using the serotonin transporter ligand [11C]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an index of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected number of brain regions. FDG uptake was normalized in each individual by dividing local FDG uptake by the maximum FDG uptake in the individual's brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at the time of PET scanning, and age at first ecstasy use, respectively. Normalized FDG uptake was reduced within the striatum and amygdala of ecstasy users when compared to controls. No statistically significant correlation of the FDG uptake and the cumulative dose of ecstasy was detected. A positive correlation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG uptake in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in former ecstasy users who did not consume ecstasy for more than 1 year. FDG uptake was significantly more affected in ecstasy users who started to consume ecstasy before the age of 18 years. In conclusion, ecstasy abuse causes long

  7. Carbon-11 and fluorine-18 chemistry devoted to molecular probes for imaging the brain with positron emission tomography.

    PubMed

    Dollé, Frédéric

    2013-01-01

    Exploration of the living human brain in real-time and in a noninvasive way was for centuries only a dream, made, however, possible today with the remarkable development during the four last decades of powerful molecular imaging techniques, and especially positron emission tomography (PET). Molecular PET imaging relies, from a chemical point of view, on the use and preparation of a positron-emitting radiolabelled probe or radiotracer, notably compounds incorporating one of two short-lived radionuclides fluorine-18 (T1/2 : 109.8 min) and carbon-11 (T1/2 : 20.38 min). The growing availability and interest for the radiohalogen fluorine-18 in radiopharmaceutical chemistry undoubtedly results from its convenient half-life and the successful use in clinical oncology of 2-[(18) F]fluoro-2-deoxy-d-glucose ([(18) F]FDG). The special interest of carbon-11 is not only that carbon is present in virtually all biomolecules and drugs allowing therefore for isotopic labelling of their chemical structures but also that a given molecule could be radiolabelled at different functions or sites, permitting to explore (or to take advantage of) in vivo metabolic pathways. PET chemistry includes production of these short-lived radioactive isotopes via nuclear transmutation reactions using a cyclotron, and is directed towards the development of rapid synthetic methods, at the trace level, for the introduction of these nuclides into a molecule, as well as the use of fast purification, analysis and formulation techniques. PET chemistry is the driving force in molecular PET imaging, and this special issue of the Journal of Labelled Compounds and Radiopharmaceuticals, which is strongly chemistry and radiochemistry-oriented, aims at illustrating, be it in part only, the state-of-the-art arsenal of reactions currently available and its potential for the research and development of specific molecular probes labelled with the positron emitters carbon-11 and fluorine-18, with optimal imaging

  8. Quantitative Analysis of Torso FDG-PET Scans by Using Anatomical Standardization of Normal Cases from Thorough Physical Examinations.

    PubMed

    Hara, Takeshi; Kobayashi, Tatsunori; Ito, Satoshi; Zhou, Xiangrong; Katafuchi, Tetsuro; Fujita, Hiroshi

    2015-01-01

    Understanding of standardized uptake value (SUV) of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) depends on the background accumulations of glucose because the SUV often varies the status of patients. The purpose of this study was to develop a new method for quantitative analysis of SUV of FDG-PET scan images. The method included an anatomical standardization and a statistical comparison with normal cases by using Z-score that are often used in SPM or 3D-SSP approach for brain function analysis. Our scheme consisted of two approaches, which included the construction of a normal model and the determination of the SUV scores as Z-score index for measuring the abnormality of an FDG-PET scan image. To construct the normal torso model, all of the normal images were registered into one shape, which indicated the normal range of SUV at all voxels. The image deformation process consisted of a whole body rigid registration of shoulder to bladder region and liver registration and a non-linear registration of body surface by using the thin-plate spline technique. In order to validate usefulness of our method, we segment suspicious regions on FDG-PET images manually, and obtained the Z-scores of the regions based on the corresponding voxels that stores the mean and the standard deviations from the normal model. We collected 243 (143 males and 100 females) normal cases to construct the normal model. We also extracted 432 abnormal spots from 63 abnormal cases (73 cancer lesions) to validate the Z-scores. The Z-scores of 417 out of 432 abnormal spots were higher than 2.0, which statistically indicated the severity of the spots. In conclusions, the Z-scores obtained by our computerized scheme with anatomical standardization of torso region would be useful for visualization and detection of subtle lesions on FDG-PET scan images even when the SUV may not clearly show an abnormality.

  9. Quantitative Positron Emission Tomography Imaging Detects Early Metabolic Remodeling in a Mouse Model of Pressure Overload Left Ventricular Hypertrophy in vivo

    PubMed Central

    Zhong, Min; Alonso, Clayton E.; Taegtmeyer, Heinrich; Kundu, Bijoy K.

    2013-01-01

    We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes

  10. The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer

    PubMed Central

    Moreno, Paula; Lara-Chica, Maribel; Soler-Torronteras, Rafael; Caro, Teresa; Medina, Manuel; Álvarez, Antonio; Salvatierra, Ángel; Muñoz, Eduardo; Calzado, Marco A.

    2015-01-01

    Objectives Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH) proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry) in human non-small cell lung cancer (NSCLC) samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features. Materials and Methods One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables. Results The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry) in non-small cell lung cancer (NSCLC). We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC) and squamous cell lung cancer (SCC). Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(18F)fluoro-D-glucose) uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates

  11. Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis

    PubMed Central

    de Oliveira, Cristiane; Patel, Krutika; Mishra, Vivek; Trivedi, Ram N.; Noel, Pawan; Singh, Abhilasha; Yaron, Jordan R.; Singh, Vijay P.

    2016-01-01

    Background Studying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP. Methods Wistar rats (300 g; 8–12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5–10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP. Results NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP

  12. PET with radiolabeled aminoacid.

    PubMed

    Crippa, F; Alessi, A; Serafini, G L

    2012-04-01

    Since the clinical introduction of FDG, neuroimaging has been the first area of PET application in oncology. Later, while FDG-PET became progressively a key imaging modality in the management of the majority of malignancies outside the brain, its neuro-oncologic indications faced some limitations because of the unfavourable characteristics of FDG as brain tumor-seeking agent. PET applications in neuro-oncology have received new effectiveness by the advent of positron-emission labelled amino acids, so that it has been coined the term "Amino acid PET" to differentiate this imaging tool from FDG-PET. Radiolabeled amino acids are a very interesting class of PET tracers with great diagnostic potential in neuro-oncology because of their low uptake in normal brain and, conversely, high uptake in most brain tumors including low-grade gliomas. The present article surveys the results obtained using L-[methyl-11C]Methionine (MET), that has been the ancestor of PET amino acid tracers and is still the most popular amino acid imaging modality in oncology, and stresses the important role that this diagnostic modality can play in the evaluation of brain tumors. However, the use of MET is restricted to PET centers with an in-house cyclotron and radiochemistry facility, because of the short half-life (20 min) of 11C. The promising results of MET have stimulated the development of 18F-labelled aminoacid tracers, particularly O-(2-18F-fluoeoethyl1)-L-tyrosine (FET), that has the same properties of MET and, thanks to the longer half-life of 18F (about 110 min), allows a distribution strategy from a production tracer site to user satellite PET centers. Considering a more widespread use of Amino acid PET, together with the recent development of integrated PET-MRI imaging systems, and the oncoming clinical validation of other interesting PET tracers, i.e. FMISO or 18F-FAZA for hypoxia imaging and FLT for tumor proliferation imaging, it can be reasonably expected that metabolic imaging

  13. 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

  14. (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma.

    PubMed

    Lapa, Constantin; Lückerath, Katharina; Kleinlein, Irene; Monoranu, Camelia Maria; Linsenmann, Thomas; Kessler, Almuth F; Rudelius, Martina; Kropf, Saskia; Buck, Andreas K; Ernestus, Ralf-Ingo; Wester, Hans-Jürgen; Löhr, Mario; Herrmann, Ken

    2016-01-01

    Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand (68)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent (68)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUVmax, SUVmean). Tumor-to-background ratios (TBR) were calculated for both PET probes. (68)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. (68)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUVmean and SUVmax of 3.0±1.5 and 3.9±2.0 respectively. Respective values for (18)F-FET were 4.4±2.0 (SUVmean) and 5.3±2.3 (SUVmax). TBR for SUVmean and SUVmax were higher for (68)Ga-Pentixafor than for (18)F-FET (SUVmean 154.0±90.7 vs. 4.1±1.3; SUVmax 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high (68)Ga-Pentixafor uptake; regions of the same tumor without apparent (68)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, (68)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, (68)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.

  15. Monitoring of Tumor Growth with [18F]-FET PET in a Mouse Model of Glioblastoma: SUV Measurements and Volumetric Approaches

    PubMed Central

    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-(2-18F-fluoroethyl)-L-tyrosine ([18F]-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. [18F]-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 [18F]-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. [18F]-FET PET with standard SUV measurements is feasible for glioma imaging in the GBM mouse model

  16. (18)F-FET PET Uptake Characteristics in Patients with Newly Diagnosed and Untreated Brain Metastasis.

    PubMed

    Unterrainer, Marcus; Galldiks, Norbert; Suchorska, Bogdana; Kowalew, Lara-Caroline; Wenter, Vera; Schmid-Tannwald, Christine; Niyazi, Maximilian; Bartenstein, Peter; Langen, Karl-Josef; Albert, Nathalie L

    2017-04-01

    In patients with brain metastasis, PET using labeled amino acids has gained clinical importance, mainly regarding the differentiation of viable tumor tissue from treatment-related effects. However, there is still limited knowledge concerning the uptake characteristics in patients with newly diagnosed and untreated brain metastases. Hence, we evaluated the uptake characteristics in these patients using dynamic O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET. Methods: Patients with newly diagnosed brain metastases without prior local therapy and (18)F-FET PET scanning were retrospectively identified in 2 centers. Static and dynamic PET parameters (maximal/mean tumor-to-brain-ratio [TBRmax/TBRmean], biologic tumor volume [BTV], and time-activity curves with minimal time to peak [TTPmin]) were evaluated and correlated with MRI parameters (maximal lesion diameter, volume of contrast enhancement) and originating primary tumor. Results: Forty-five brain metastases in 30 patients were included. Forty of 45 metastases (89%) had a TBRmax ≥ 1.6 and were classified as (18)F-FET-positive (median TBRmax, 2.53 [range, 1.64-9.47]; TBRmean, 1.86 [range, 1.63-5.48]; and BTV, 3.59 mL [range, 0.04-23.98 mL], respectively). In 39 of 45 brain metastases eligible for dynamic analysis, a wide range of TTPmin was observed (median, 22.5 min; range, 4.5-47.5 min). All (18)F-FET-negative metastases had a diameter of ≤ 1.0 cm, whereas metastases with a > 1.0 cm diameter all showed pathologic (18)F-FET uptake, which did not correlate with lesion size. The highest variability of uptake intensity was observed within the group of melanoma metastases. Conclusion: Untreated metastases predominantly show increased (18)F-FET uptake, and only a third of metastases < 1.0 cm were (18)F-FET-negative, most likely because of scanner resolution and partial-volume effects. In metastases > 1.0 cm, (18)F-FET uptake intensity was highly variable and independent of tumor size (even intraindividually). (18

  17. Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma

    PubMed Central

    HAYLOCK, ANNA-KARIN; SPIEGELBERG, DIANA; MORTENSEN, ANJA C.; SELVARAJU, RAM K.; NILVEBRANT, JOHAN; ERIKSSON, OLOF; TOLMACHEV, VLADIMIR; NESTOR, MARIKA V.

    2016-01-01

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodis-tribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using

  18. First-in-Human Phase I Trial of Two Schedules of OSI-930, a Novel Multikinase Inhibitor, Incorporating Translational Proof-of-Mechanism Studies

    PubMed Central

    Yap, Timothy A.; Arkenau, Hendrik-Tobias; Camidge, D. Ross; George, Suzanne; Serkova, Natalie J.; Gwyther, Stephen J.; Spratlin, Jennifer L.; Lal, Rohit; Spicer, James; Desouza, Nandita M.; Leach, Martin O.; Chick, Jon; Poondru, Srinivasu; Boinpally, Ramesh; Gedrich, Richard; Brock, Katie; Stephens, Andrew; Eckhardt, S. Gail; Kaye, Stan B.; Demetri, George; Scurr, Michelle

    2013-01-01

    Purpose OSI-930 is a novel, potent, oral small-molecule receptor tyrosine kinase inhibitor, predominantly against VEGF receptors (VEGFR), c-Kit, and platelet-derived growth factor receptors. A phase I trial was undertaken to determine safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and antitumor activity of OSI-930 in patients with advanced solid tumors. Experimental Design OSI-930 was administered once or twice a day using a modified accelerated titration design. Pharmacokinetics and plasma soluble VEGFR2 (sVEGFR2) studies were undertaken. Dynamic contrast-enhanced MRI (DCE-MRI) and 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) MTD expansion cohorts were conducted. Results Fifty-eight patients received OSI-930 in 2 schedules; once a day schedule: 12 patients at doses up to 1,600 mg without reaching MTD; twice a day schedule: 46 patients at 400 mg (n = 7), 500 mg (n = 31), and 600 mg (n =8). Dose-limiting toxicities were observed at 600 mg twice a day (n =3): G3 rash (n =2) and G4 γ-glutamyltransferase, establishing the MTD at 500 mg twice a day. Common G1–2 toxicities included fatigue, diarrhea, nausea, and rash. Antitumor responses were seen in 2 patients with advanced ovarian cancer [Response Evaluation Criteria in Solid Tumors (RECIST) partial response (PR) (n = 1); GCIG CA125 response (n = 1)]. Eleven of 19 heavily pretreated imatinib-resistant patients with gastrointestinal stromal tumors achieved RECIST stable disease (median duration: 126 days), with FDG-PET scans showing PRs in 4 of 9 patients. OSI-930 exposure increased with dose; substantial decreases in sVEGFR levels were observed with OSI-930 twice a day doses ≥400 mg, while DCE-MRI responses were shown in 4 of 6 patients. Conclusions OSI-930 is safe and well tolerated, with pharmacokinetic–pharmacodynamic data supporting proof-of-mechanism with clinically relevant antitumor activity. PMID:23403628

  19. Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy

    PubMed Central

    Na, Feifei; Wang, Jingwen; Li, Cong; Deng, Lei; Xue, Jianxin

    2014-01-01

    Introduction: The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect. Methods: We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy. Results: Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively. Conclusion: Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC. PMID:24787963

  20. Quantification of metabotropic glutamate subtype 5 receptors in the brain by an equilibrium method using 18F-SP203.

    PubMed

    Kimura, Yasuyuki; Siméon, Fabrice G; Zoghbi, Sami S; Zhang, Yi; Hatazawa, Jun; Pike, Victor W; Innis, Robert B; Fujita, Masahiro

    2012-02-01

    A new PET ligand, 3-fluoro-5-(2-(2-(18)F-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (18F-SP203) can quantify metabotropic glutamate subtype 5 receptors (mGluR5) in human brain by a bolus injection and kinetic modeling. As an alternative approach to a bolus injection, binding can simply be measured as a ratio of tissue to metabolite-corrected plasma at a single time point under equilibrium conditions achieved by administering the radioligand with a bolus injection followed by a constant infusion. The purpose of this study was to validate the equilibrium method as an alternative to the standard kinetic method for measuring 18F-SP203 binding in the brain. Nine healthy subjects were injected with 18F-SP203 using a bolus plus constant infusion for 300 min. A single ratio of bolus-to-constant infusion (the activity of bolus equaled to that of infusion over 219 min) was applied to all subjects to achieve equilibrium in approximately 120 min. As a measure of ligand binding, we compared total distribution volume (VT) calculated by the equilibrium and kinetic methods in each scan. The equilibrium method calculated VT by the ratio of radioactivity in the brain to the concentration of 18F-SP203 in arterial plasma at 120 min, and the kinetic method calculated VT by a two-tissue compartment model using brain and plasma dynamic data from 0 to 120 min. VT obtained via the equilibrium method was highly correlated with VT obtained via kinetic modeling. Inter-subject variability of VT obtained via the equilibrium method was slightly smaller than VT obtained via the kinetic method. VT obtained via the equilibrium method was ~10% higher than VT obtained via the kinetic method, indicating a small difference between the measurements. Taken together, the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18F-SP203 to measure mGluR5. Although small differences in the measurements obtained via the

  1. 18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy

    PubMed Central

    Topakian, Raffi; Pichler, Robert

    2016-01-01

    Abstract Background Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20–40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). PET/CT can predict surgical outcome in patients with refractory epilepsy. The aim of the article is to review the current role of routinely used tracer 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) as well as non routinely used 18F-Flumazenil (18F-FMZ) tracers PET/CT in patients with refractory epilepsy. Conclusions Functional information delivered by PET and the morphologic information delivered by CT or MRI are essential in presurgical evaluation of epilepsy. Nowadays 18F-FDG PET/CT is a routinely performed imaging modality in localization of the ictal onset zone in patients with refractory epilepsy who are unresponsive to medication therapy. Unfortunately, 18F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate precisely with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. Benzodiazepine-receptor imaging is a promising alternative in nuclear medicine imaging of epileptogenic focus. The use of 11C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. Therefore, 18F-FMZ might be established as one of the tracers of choice for patients

  2. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice

    DOE PAGES

    Taylor, Kristina; Lemon, Jennifer A.; Phan, Nghi; ...

    2014-05-28

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancermore » risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy 18F-FDG, 4 Gy γ-rays, 10 mGy 18F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from 18F-FDG, with respect to malignancy, is approximately 1. Furthermore, when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.« less

  3. Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers.

    PubMed

    Mosci, Camila; Kumar, Meena; Smolarz, Kamilla; Koglin, Norman; Stephens, Andrew W; Schwaiger, Markus; Gambhir, Sanjiv S; Mittra, Erik S

    2016-06-01

    Purpose To evaluate the normal biodistribution and kinetics of (S)-4-(3-[18F]fluoropropyl)-l-glutamic acid ((18)F FSPG) in healthy volunteers and to compare (18)F FSPG mean and maximum standardized uptake values (SUVmean and SUVmax, respectively) with those of (18)F fluorodeoxyglucose (FDG) across a variety of organs. Materials and Methods This protocol was reviewed and approved by all appropriate regulatory authorities. An 8-mCi (±10%) dose of (18)F FSPG was given to five subjects (three women, two men), and seven whole-body positron emission tomography (PET) scans were performed 5, 10, 20, 30, 45, 150, and 240 minutes after injection. Regions of interest were analyzed on the resultant (18)F FSPG images to evaluate the kinetics of this radiotracer. The images obtained 45 minutes after injection were used to measure SUVmean and SUVmax in additional regions of the body. These values were compared with similar values obtained with (18)F FDG PET published previously. Descriptive statistics, including average and standard deviation across the five subjects, were used. (18)F FSPG SUVmean and SUVmax were compared. Results On the (18)F FSPG images obtained 45 minutes after injection, there was only low-grade background activity in the majority of analyzed regions. Prominent activity was seen throughout the pancreas. Clearance of the radiotracer through the kidneys and collection in the bladder also were seen. SUV quantification shows notable differences between (18)F FSPG and (18)F FDG in the pancreas ((18)F FSPG SUVmean, 8.2; (18)F FDG SUVmean, 1.3), stomach ((18)F FSPG SUVmax, 3.6; (18)F FDG SUVmax, 1.6), and brain ((18)F FSPG SUVmean, 0.08; (18)F FDG SUVmean, 7.8). The kinetic data showed rapid clearance of the radiotracer from the blood pool and most organs, except the pancreas. Conclusion (18)F FSPG is a PET radiopharmaceutical characterized by rapid clearance from most healthy tissues, except the pancreas and kidneys. A consistent biodistribution pattern was

  4. HPLC and TLC methods for analysis of [(18)F]FDG and its metabolites from biological samples.

    PubMed

    Rokka, Johanna; Grönroos, Tove J; Viljanen, Tapio; Solin, Olof; Haaparanta-Solin, Merja

    2017-03-24

    The most used positron emission tomography (PET) tracer, 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG), is a glucose analogue that is used to measure tissue glucose consumption. Traditionally, the Sokoloff model is the basis for [(18)F]FDG modeling. According to this model, [(18)F]FDG is expected to be trapped in a cell in the form of [(18)F]FDG-6-phosphate ([(18)F]FDG-6-P). However, several studies have shown that in tissues, [(18)F]FDG metabolism goes beyond [(18)F]FDG-6-P. Our aim was to develop radioHPLC and radioTLC methods for analysis of [(18)F]FDG metabolites from tissue samples. The radioHPLC method uses a sensitive on-line scintillation detector to detect radioactivity, and the radioTLC method employs digital autoradiography to detect the radioactivity distribution on a TLC plate. The HPLC and TLC methods were developed using enzymatically in vitro-produced metabolites of [(18)F]FDG as reference standards. For this purpose, three [(18)F]FDG metabolites were synthesized: [(18)F]FDG-6-P, [(18)F]FD-PGL, and [(18)F]FDG-1,6-P2. The two methods were evaluated by analyzing the [(18)F]FDG metabolic profile from rodent ex vivo tissue homogenates. The HPLC method with an on-line scintillation detector had a wide linearity in a range of 5Bq-5kBq (LOD 46Bq, LOQ 139Bq) and a good resolution (Rs ≥1.9), and separated [(18)F]FDG and its metabolites clearly. The TLC method combined with digital autoradiography had a high sensitivity in a wide range of radioactivity (0.1Bq-2kBq, LOD 0.24Bq, LOQ 0.31Bq), and multiple samples could be analyzed simultaneously. As our test and the method validation with ex vivo samples showed, both methods are useful, and at best they complement each other in analysis of [(18)F]FDG and its radioactive metabolites from biological samples.

  5. Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma.

    PubMed

    Haylock, Anna-Karin; Spiegelberg, Diana; Mortensen, Anja C; Selvaraju, Ram K; Nilvebrant, Johan; Eriksson, Olof; Tolmachev, Vladimir; Nestor, Marika V

    2016-02-01

    We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of 125I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with 124I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodistribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of 124I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to 18F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using

  6. Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice

    DOE PAGES

    Taylor, Kristina; Lemon, Jennifer A.; Boreham, Douglas R.

    2014-05-28

    Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[18F] fluoro-2-deoxy-d-glucose (18F-FDG), however little research has been conducted on the biological effects of 18F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from 18F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from 18F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of 18F-FDG, mice were injected with a rangemore » of activities of 18F-FDG (0–14.80 MBq) or irradiated with Cs-137 γ-rays (0–100 mGy). The adaptive response was investigated 24 h after the 18F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the 18F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq 18F-FDG relative to controls (P < 0.019). A 0.74 MBq 18F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical 18F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. Lastly, the 18F-FDG RBE was <1.0, indicating that the mixed radiation quality

  7. Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice.

    PubMed

    Taylor, Kristina; Lemon, Jennifer A; Phan, Nghi; Boreham, Douglas R

    2014-07-01

    There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV β+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy (18)F-FDG, 4 Gy γ-rays, 10 mGy (18)F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from (18)F-FDG, with respect to malignancy, is approximately 1. However; when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.

  8. Nuclear medicine imaging of bone infections.

    PubMed

    Love, C; Palestro, C J

    2016-07-01

    Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been

  9. Expedited Synthesis of Fluorine-18 Labeled Phenols. A Missing Link in PET Radiochemistry

    SciTech Connect

    Katzenellenbogen, John A.; Zhou, Dong

    2015-03-26

    (diazocyclohexenones) by a novel reaction sequence that uses fluoride ion as a precursor and various activating electrophiles, and we have improved methods for the preparation of heterodiaryl iodonium salts. Both methods have been used to prepare interesting potential radiotracers. Other advances have been made in labeling dendrimeric nanoparticle structures of increasing interest for multimodal imaging and in advancing labeling through fluorosilane bonds. Thus, the progress we have made substantially fills the significant gap in PET radiochemistry that we originally identified, and it provides for the field new methodology that can be applied to a number of current challenges, including the preparation of several molecules of interest as radiotracers, such as 2-[18F]Fluoroestradiol (2-FES) and m-fluorotyrosine, which we have illustrated. These methods can be used by any skilled radiochemist interesting in preparing these agents or similar fluorine-18 labeled electron-rich arene systems of interested for PET biological imaging in the most general sense.

  10. A study of shape-dependent partial volume correction in pet imaging using ellipsoidal phantoms fabricated via rapid prototyping

    NASA Astrophysics Data System (ADS)

    Mille, Matthew M.

    Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) is being increasingly recognized as an important tool for quantitative assessment of tumor response because of its ability to capture functional information about the tumor's metabolism. However, despite many advances in PET technology, measurements of tumor radiopharmaceutical uptake in PET are still challenged by issues of accuracy and consistency, thereby compromising the use of PET as a surrogate endpoint in clinical trials. One limiting component of the overall uncertainty in PET is the relatively poor spatial resolution of the images which directly affects the accuracy of the tumor radioactivity measurements. These spatial resolution effects, colloquially known as the partial volume effect (PVE), are a function of the characteristics of the scanner as well as the tumor being imaged. Previous efforts have shown that the PVE depends strongly on the tumor volume and the background-to-tumor activity concentration ratio. The PVE is also suspected to be a function of tumor shape, although to date no systematic study of this effect has been performed. This dissertation seeks to help fill the gap in the current knowledge about the shape-dependence of the PVE by attempting to quantify, through both theoretical calculation and experimental measurement, the magnitude of the shape effect for ellipsoidal tumors. An experimental investigation of the tumor shape effect necessarily requires tumor phantoms of multiple shapes. Hence, a prerequisite for this research was the design and fabrication of hollow tumor phantoms which could be filled uniformly with radioactivity and imaged on a PET scanner. The phantom fabrication was achieved with the aid of stereolithography and included prolate ellipsoids of various axis ratios. The primary experimental method involved filling the tumor phantoms with solutions of 18F whose activity concentrations were known and traceable to primary radioactivity standards