18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scanning in Diagnosing Vascular Prosthetic Graft Infection

PubMed Central

Saleem, Ben R.; Pol, Robert A.; Slart, Riemer H. J. A.; Reijnen, Michel M. P. J.; Zeebregts, Clark J.

2014-01-01

Vascular prosthetic graft infection (VPGI) is a severe complication after vascular surgery. CT-scan is considered the diagnostic tool of choice in advanced VPGI. The incidence of a false-negative result using CT is relatively high, especially in the presence of low-grade infections. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning has been suggested as an alternative for the diagnosis and assessment of infectious processes. Hybrid 18F-FDG PET/CT has established the role of 18F-FDG PET for the assessment of suspected VPGI, providing accurate anatomic localization of the site of infection. However, there are no clear guidelines for the interpretation of the uptake patterns of 18F-FDG as clinical tool for VPGI. Based on the available literature it is suggested that a linear, diffuse, and homogeneous uptake should not be regarded as an infection whereas focal or heterogeneous uptake with a projection over the vessel on CT is highly suggestive of infection. Nevertheless, 18F-FDG PET and 18F-FDG PET/CT can play an important role in the detection of VPGI and monitoring response to treatment. However an accurate uptake and pattern recognition is warranted and cut-off uptake values and patterns need to be standardized before considering the technique to be the new standard. PMID:25210712

Unusual Asymptomatic Fluorodeoxyglucose Avid Pheochromocytoma in a Case of Myxoid Liposarcoma of the Extremity on 18-F Fluorodeoxyglucose Positron Emission Tomography-computed Tomography.

PubMed

Shivdasani, Divya; Singh, Natasha; Pereira, Melvika; Zade, Anand

2017-01-01

Sarcomas are a heterogeneous group of rare tumors and arise either from soft tissue or from bone. Soft-tissue sarcomas (STSs) initially metastasize to the lungs. Metastases to extrapulmonary sites such as liver, brain, and soft tissue distant from primary tumor usually develop later. However, cases with isolated adrenal metastasis without disseminated disease have been reported in literature. We present a case of primary myxoid liposarcoma of the lower limb, in which staging 18 -F fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan detected a suspicious FDG avid adrenal lesion which eventually on resection was diagnosed as asymptomatic pheochromocytoma. Pheochromocytomas have been reported to demonstrate FDG uptake mimicking metastasis. Hence, while interpreting FDG PET-CT scans in the context of STSs, both the extrapulmonary metastatic potential of aggressive histological subtypes of sarcoma and rare possibility of FDG avid coexistent benign tumor should be taken into consideration.

Clusters of Low (18)F-Fluorodeoxyglucose Uptake Voxels in Combat Veterans with Traumatic Brain Injury and Post-Traumatic Stress Disorder.

PubMed

Buchsbaum, Monte S; Simmons, Alan N; DeCastro, Alex; Farid, Nikdokht; Matthews, Scott C

2015-11-15

Individuals with mild traumatic brain injury (TBI) show diminished metabolic activity when studied with positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Since blast injury may not be localized in the same specific anatomical areas in every patient or may be diffuse, significance probability mapping may be vulnerable to false-negative detection of abnormalities. To address this problem, we used an anatomically independent measure to assess PET scans: increased numbers of contiguous voxels that are 2 standard deviations below values found in an uninjured control group. We examined this in three age-matched groups of male patients: 16 veterans with a history of mild TBI, 17 veterans with both mild TBI and post-traumatic stress disorder (PTSD), and 15 veterans without either condition. After FDG administration, subjects performed a modified version of the California Verbal Learning Task. Clusters of low uptake voxels were identified by computing the mean and standard deviation for each voxel in the healthy combat veteran group and then determining the voxel-based z-score for the patient groups. Abnormal clusters were defined as those that contained contiguous voxels with a z-score <-2. Patients with mild TBI alone and patients with TBI+PTSD had larger clusters of low uptake voxels, and cluster size significantly differentiated the mild TBI groups from combat controls. Clusters were more irregular in shape in patients, and patients also had a larger number of low-activity voxels throughout the brain. In mild TBI and TBI+PTSD patients, but not healthy subjects, cluster volume was significantly correlated with verbal learning during FDG uptake.

Long-term quality assurance of [(18)F]-fluorodeoxyglucose (FDG) manufacturing.

PubMed

Gaspar, Ludovit; Reich, Michal; Kassai, Zoltan; Macasek, Fedor; Rodrigo, Luis; Kruzliak, Peter; Kovac, Peter

2016-01-01

Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of (18)F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade "A" isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade "A" isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [(18)F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems.

Long-term quality assurance of [18F]-fluorodeoxyglucose (FDG) manufacturing

PubMed Central

Gaspar, Ludovit; Reich, Michal; Kassai, Zoltan; Macasek, Fedor; Rodrigo, Luis; Kruzliak, Peter; Kovac, Peter

2016-01-01

Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of 18F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade “A” isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade “A” isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [18F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems. PMID:27508102

False-positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography in a patient with metallic implants following chondrosarcoma resection.

PubMed

Zhou, P U; Tang, Jinliang; Zhang, Dong; Li, Guanghui

2016-05-01

Positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG) has been used for the staging and evaluation of recurrence in cancer patients. We herein report a false-positive result of 18 F-FDG PET/computed tomography (CT) scan in a patient following chondrosarcoma resection and metallic implanting. A 35-year-old male patient with chondrosarcoma of the left iliac bone underwent radical resection, metal brace implanting and radiotherapy. A high uptake of 18 F-FDG was observed in the metallic implants and adjacent tissue during PET/CT scanning in the 5th year of follow-up. Tissue biopsy and follow-up examination identified no tumor recurrence or infection at these sites, suggesting that the results of 18 F-FDG PET/CT must be interpreted with caution in cancer patients with metallic implants.

68Gallium-Arginine-Glycine-Aspartic Acid and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Chondroblastic Osteosarcoma of the Skull.

PubMed

Orunmuyi, Akintunde; Modiselle, Moshe; Lengana, Thabo; Ebenhan, Thomas; Vorster, Mariza; Sathekge, Mike

2017-09-01

We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both 18 [F]fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) and 68 Gallium-arginine-glycine-aspartic acid ( 68 Ga-RGD) PET/CT. The 18 F-FDG PET/CT did not demonstrate the tumour, whereas the 68 Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. 68 Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of 18 F-FDG PET in a setting of low glycolytic activity.

False-positive 18F-fluorodeoxyglucose positron emission tomography/computed tomography in a patient with metallic implants following chondrosarcoma resection

PubMed Central

ZHOU, PU; TANG, JINLIANG; ZHANG, DONG; LI, GUANGHUI

2016-01-01

Positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (18F-FDG) has been used for the staging and evaluation of recurrence in cancer patients. We herein report a false-positive result of 18F-FDG PET/computed tomography (CT) scan in a patient following chondrosarcoma resection and metallic implanting. A 35-year-old male patient with chondrosarcoma of the left iliac bone underwent radical resection, metal brace implanting and radiotherapy. A high uptake of 18F-FDG was observed in the metallic implants and adjacent tissue during PET/CT scanning in the 5th year of follow-up. Tissue biopsy and follow-up examination identified no tumor recurrence or infection at these sites, suggesting that the results of 18F-FDG PET/CT must be interpreted with caution in cancer patients with metallic implants. PMID:27123290

Impact of physiological hormonal fluctuations on 18F-fluorodeoxyglucose uptake in breast cancer.

PubMed

Miyake, Kanae K; Nakamoto, Yuji; Saji, Shigehira; Sugie, Tomoharu; Kurihara, Kensuke; Kanao, Shotaro; Ikeda, Debra M; Toi, Masakazu; Togashi, Kaori

2018-06-01

Premenopausal physiologic steroid levels change cyclically, in contrast to steady state low levels seen in postmenopausal patients. The purpose of this study was to evaluate whether 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake in breast cancer is influenced by physiological hormonal fluctuations. A total of 160 primary invasive breast cancers from 155 females (54 premenopausal, 101 postmenopausal) who underwent 18 F-FDG positron emission tomography/computed tomography before therapy were retrospectively analyzed. The maximal standardized uptake values (SUVmax) of tumors were compared with menstrual phases and menopausal status according to the following subgroups: 'luminal A-like,' 'luminal B-like,' and 'non-luminal.' Additionally, the effect of estradiol (E2) on 18 F-FDG uptake in breast cancer cells was evaluated in vitro. Among premenopausal patients, SUVmax during the periovulatory-luteal phase was significantly higher than that during the follicular phase in luminal A-like tumors (n = 25, p = 0.004), while it did not differ between the follicular phase and the periovulatory-luteal phase in luminal B-like (n = 24) and non-luminal tumors (n = 7). Multiple regression analysis showed menstrual phase, tumor size, and Ki-67 index are independent predictors for SUVmax in premenopausal luminal A-like tumors. There were no significant differences in SUVmax between pre- and postmenopausal patients in any of the subgroups. In in vitro studies, uptake in estrogen receptor-positive cells was significantly augmented when E2 concentration was increased from 0.01 to ≥ 1 nM. Our data suggest that 18 F-FDG uptake may be impacted by physiological hormonal fluctuations during menstrual cycle in luminal A-like cancers, and that E2 could be partly responsible for these events.

Pleuroperitoneal Mesothelioma: A Rare Entity on 18F-FDG PET/CT

PubMed Central

Sahoo, Manas Kumar; Mukherjee, Anirban; Girish; Parida, Kumar; Agarwal, Krishan Kant; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

2017-01-01

Pleuroperitoneal mesothelioma is an extremely rare entity. Only few cases are reported worldwide. We hereby represent a case of pleural mesothelioma referred for F-18-Fluorodeoxyglucose positron emission tomography/computed tomography for response evaluation. Diffuse F-18-Fluorodeoxyglucose avid peritoneal and omental thickening noted which subsequently turned out to be mesothelial involvement on peritoneal biopsy. This case demonstrates the role of F-18-Fluorodeoxyglucose positron emission tomography/computed tomography in detecting other sites of involvement in case of malignant mesothelioma. PMID:28242997

Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study

PubMed Central

Andrzejewski, Piotr; Baltzer, Pascal; Polanec, Stephan H.; Sturdza, Alina; Georg, Dietmar; Helbich, Thomas H.; Karanikas, Georgios; Grimm, Christoph; Polterauer, Stephan; Poetter, Richard; Wadsak, Wolfgang; Mitterhauser, Markus; Georg, Petra

2016-01-01

Objectives To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Materials and Methods Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. Results All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05–0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. Conclusion MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT. PMID:27167829

Multiparametric [18F]Fluorodeoxyglucose/ [18F]Fluoromisonidazole Positron Emission Tomography/ Magnetic Resonance Imaging of Locally Advanced Cervical Cancer for the Non-Invasive Detection of Tumor Heterogeneity: A Pilot Study.

PubMed

Pinker, Katja; Andrzejewski, Piotr; Baltzer, Pascal; Polanec, Stephan H; Sturdza, Alina; Georg, Dietmar; Helbich, Thomas H; Karanikas, Georgios; Grimm, Christoph; Polterauer, Stephan; Poetter, Richard; Wadsak, Wolfgang; Mitterhauser, Markus; Georg, Petra

2016-01-01

To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05-0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.

F-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Appearance of Extramedullary Hematopoesis in a Case of Primary Myelofibrosis

PubMed Central

Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi; Das, Chandan Jyoti; Shamim, Shamim Ahmed

2017-01-01

A 44-year-old female with known primary myelofibrosis presented with shortness of breath. High Resolution Computed Tomography thorax revealed large heterogeneously enhancing extraparenchymal soft tissue density mass involving bilateral lung fields. F-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography revealed mildly FDG avid soft tissue density mass with specks of calcification involving bilateral lung fields, liver, and spleen. Subsequent histopathologic evaluation from the right lung mass was suggestive of extramedullary hematopoesis. PMID:28533647

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

PubMed

Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

2015-05-01

The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

Cardiac Sarcoidosis Concomitant with Large-vessel Aortitis Detected by 18F-fluorodeoxyglucose Positron Emission Tomography.

PubMed

Higuchi, Yoshihiro; Kimoto, Yasutaka; Tanoue, Rika; Tokunou, Tomotake; Tomonari, Kenichiro; Maeda, Toyoki; Horiuchi, Takahiko

2018-06-01

We herein report a case of concurrent cardiac sarcoidosis and large-vessel aortitis detected by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and followed up during immunosuppressive therapy. After high-dose prednisolone administration (1 mg/kg), serial FDG-PET showed that almost all of the abnormal FDG uptake in the heart and extracardiac region, including the abdominal to bilateral iliac arteries, had been disappeared. During the tapering of prednisolone, additive methotrexate therapy was needed to treat the recurrence of cardiac sarcoidosis. FDG-PET is a useful tool for detecting cardiac sarcoidosis concomitant with large-vessel aortitis and monitoring the effectiveness of immunosuppressive therapy.

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

PubMed

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

2016-06-28

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

Endoscopic and histopathological analysis of incidental focal colorectal 18 F-fluorodeoxyglucose uptake in PET/CT scan: Colonoscopic evaluation is warranted.

PubMed

Valente, Michael A

2018-03-01

Unexpected focal colorectal 18  F-fluorodeoxyglucose uptake has become a common clinical dilemma. The aim of this study was to identify the clinical significance of incidentally detected colorectal lesions on PET/CT scans by comparing positive PET/CT findings with endoscopic and histopathological analysis. A retrospective analysis of a colonoscopy database was reviewed. All patients that underwent colonoscopy secondary to focal incidental uptake on PET/CT were evaluated. PET/CT findings were correlated with endoscopic and histopathological results. 84 patients underwent colonoscopy secondary to incidental focal colorectal uptake on PET/CT. A total of 63 patients had an endoscopic and histological confirmation of the area of abnormality, for a positive predictive value of 75%. Newly diagnosed colorectal carcinoma was discovered in 13 patients (15.4%) and forty-four patients (52.3%) were discovered to have a premalignant lesion. Incidental focal colorectal uptake of 18  F-fluorodeoxyglucose is associated with a substantial risk of underlying neoplastic colorectal lesions. Early identification of these lesions may alter patient management and treatment plans. Copyright © 2017 Elsevier Inc. All rights reserved.

Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with (/sup 18/F)fluorodeoxyglucose

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

Friedland, R.P.; Budinger, T.F.; Ganz, E.

1983-08-01

Alzheimer disease is the most common cause of dementia in adults. Despite recent advances in our understanding of its anatomy and chemistry, we remain largely ignorant of its pathogenesis, physiology, diagnosis, and treatment. Dynamic positron emission tomography using (/sup 18/F)fluorodeoxyglucose (FDG) was performed on the Donner 280-crystal ring in 10 subjects with dementia of the Alzheimer type and six healthy age-matched controls. Ratios comparing mean counts per resolution element in frontal, temporoparietal, and entire cortex regions in brain sections 10 mm thick obtained 40-70 min following FDG injection showed relatively less FDG uptake in the temporoparietal cortex bilaterally in allmore » the Alzheimer subjects (p less than 0.01). Left-right alterations were less prominent than the anteroposterior changes. This diminished uptake was due to lowered rates of FDG use and suggests that the metabolic effects of Alzheimer disease are most concentrated in the temporoparietal cortex. Positron emission tomography is a most powerful tool for the noninvasive in vivo assessment of cerebral pathophysiology in dementia.« less

[18F]-Fluorodeoxyglucose-Positron Emission Tomography in Rats with Prolonged Cocaine Self-Administration Suggests Potential Brain Biomarkers for Addictive Behavior

PubMed Central

Cannella, Nazzareno; Cosa-Linan, Alejandro; Roscher, Mareike; Takahashi, Tatiane T.; Vogler, Nils; Wängler, Björn; Spanagel, Rainer

2017-01-01

The DSM5-based dimensional diagnostic approach defines substance use disorders on a continuum from recreational drug use to habitual and ultimately addicted behavior. Biomarkers that are indicative of recreational drug use and addicted behavior are lacking. We performed a translational [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) study in the multi-dimensional 0/3crit model of cocaine addiction. Addict-like (3crit) and non-addict-like (0crit) rats, which shared identical life conditions and levels of cocaine self-administration, were acquired for FDG-PET under baseline conditions and following cocaine and yohimbine challenges. Compared to cocaine-naïve control rats, 0crit animals showed higher glucose uptake in the caudate putamen (CPu) and medial prefrontal cortex (mPFC) respect to naïve controls. 3crit animals did not show this adaptive higher glucose utilization, but had lower uptake in several cortical areas. Both cocaine and yohimbine challenges affected glucose uptake in control rats in several brain sites, but not in 0crit and 3crit rats, indicating that impaired glucose mobilization in response to these challenges is not specifically associated with addictive behavior. Compared to 0crit, 3crit rats showed higher reinstatement responses, which were negatively associated with glucose uptake in the ventral tegmental area. Data indicate that cocaine non-addict- and addict-like phenotypes are associated with several potential biomarkers. Specifically, we propose that increased glucose uptake in the CPu and mPFC is a function of controlled drug use, whereas a loss of striatal and prefrontal metabolic activity and reduced uptake in cortical areas are indicative of addictive behavior. PMID:29163237

[18F]-Fluorodeoxyglucose-Positron Emission Tomography in Rats with Prolonged Cocaine Self-Administration Suggests Potential Brain Biomarkers for Addictive Behavior.

PubMed

Cannella, Nazzareno; Cosa-Linan, Alejandro; Roscher, Mareike; Takahashi, Tatiane T; Vogler, Nils; Wängler, Björn; Spanagel, Rainer

2017-01-01

The DSM5-based dimensional diagnostic approach defines substance use disorders on a continuum from recreational drug use to habitual and ultimately addicted behavior. Biomarkers that are indicative of recreational drug use and addicted behavior are lacking. We performed a translational [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) study in the multi-dimensional 0/3crit model of cocaine addiction. Addict-like (3crit) and non-addict-like (0crit) rats, which shared identical life conditions and levels of cocaine self-administration, were acquired for FDG-PET under baseline conditions and following cocaine and yohimbine challenges. Compared to cocaine-naïve control rats, 0crit animals showed higher glucose uptake in the caudate putamen (CPu) and medial prefrontal cortex (mPFC) respect to naïve controls. 3crit animals did not show this adaptive higher glucose utilization, but had lower uptake in several cortical areas. Both cocaine and yohimbine challenges affected glucose uptake in control rats in several brain sites, but not in 0crit and 3crit rats, indicating that impaired glucose mobilization in response to these challenges is not specifically associated with addictive behavior. Compared to 0crit, 3crit rats showed higher reinstatement responses, which were negatively associated with glucose uptake in the ventral tegmental area. Data indicate that cocaine non-addict- and addict-like phenotypes are associated with several potential biomarkers. Specifically, we propose that increased glucose uptake in the CPu and mPFC is a function of controlled drug use, whereas a loss of striatal and prefrontal metabolic activity and reduced uptake in cortical areas are indicative of addictive behavior.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2005-06-01

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

The role of 18F-fluorodeoxyglucose positron emission tomography in the management of patients with pancreatic adenocarcinoma.

PubMed

Kadhim, Lujaien A; Dholakia, Avani S; Herman, Joseph M; Wahl, Richard L; Chaudhry, Muhammad A

2013-12-01

Pancreatic cancer continues to have a grim prognosis with 5-year survival rates at less than 5 %. It is a particularly challenging health problem given these poor survival outcomes, aggressive tumor biology, and late onset of symptoms. Most patients present with advanced unresectable cancer however, margin-negative resection provides a rare chance for cure for patients with resectable disease. The standard imaging modality for the diagnosis and management of pancreatic cancer is contrast-enhanced multidetector computed tomography. Remarkable advances in CT technology have led to improvements in the ability to detect small tumors and intricate vasculature involvement by the tumor, yet CT is still restricted to providing a morphological portrait of the tumor. Diagnosis can be challenging due to similar appearance of certain benign and malignant disease. Distant metastatic disease can be silent on CT leading to improper staging, and thus management, of certain patients. Furthermore, radiation-induced fibrosis and necrosis complicate assessment of treatment response by CT alone. F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) is becoming a prevalent tool employed by physicians to improve accuracy in these clinical scenarios. Malignant transformation causes a high metabolic activity of cancer cells. 18 F-FDG-PET captures this functional activity of malignancies by capturing areas with high glucose utilization rates. Imaging function rather than morphological appearance, 18 F-FDG-PET has a unique role in the management of oncology patients with the ability to detect regions of tumor involvement that may be silent on conventional imaging. Literature on the sensitivity and specificity of 18 F-FDG-PET fails to reach a consensus, and improvements resulting in hybridization of 18 F-FDG-PET and CT imaging techniques are preliminary. Here we review the potential role of 18 F-FDG-PET and PET/CT in improving accuracy in the initial evaluation and subsequent

Emission computed tomography of /sup 18/F-fluorodeoxyglucose and /sup 13/N-ammonia in stroke and epilepsy

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

Kuhl, D.E.; Phelps, M.E.; Engel, J. Jr.

1980-01-01

The ECAT Positron Tomograph was used to scan normal control subjects, stroke patients at various times during recovery, and patients with partial epilepsy during EEG monitoring. /sup 18/F-fluorodeoxyglucose (/sup 18/FDG) and /sup 13/N-Ammonia (/sup 13/NH/sub 3/) were used as indicators of abnormalities in local cerebral glucose utilization (LCMR/sub glc/) and relative perfusion, respectively. Hypometabolism, due to deactivation or minimal damage, was demonstrated with the /sup 18/FDG scan in deep structures and broad zones of cerebral cortex which appeared normal on x-ray CT (XCT) and /sup 99m/Tc pertechnetate scans. In patients with partial epilepsy, who had unilateral or focal electrical abnormalities,more » interictal /sup 18/FDG scan patterns clearly showed localized regions of decreased (20 to 50%) LCMR/sub glc/, which correlated anatomically with the eventual EEG localization.« less

[Use of positron-emission tomography with F18-fluorodeoxyglucose for the assessment of lung lesions suspicious of malignancy].

PubMed

Jofré, M Josefina; Massardo, Teresa; González, Patricio; Canessa, José; Sierralta, Paulina; Humeres, Pamela; Galaz, Rodrigo; Valdebenito, Robert

2005-05-01

Positron-emission tomography (PET) with F18-fluorodeoxyglucose (FDG) is very helpful in the evaluation and management of lung lesions. It is specially useful for the characterization of solitary nodules, for the staging, evaluation of recurrence and therapeutic response in non-small cell lung cancer, for the evaluation of small cell lung cancer and for the assessment of pulmonary metastases. This article is a literature review on PET with FDG in lung cancer. A preliminary analysis of PET results at the Military Hospital in Santiago, Chile, is also presented.

SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

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

Ma, C; Yin, Y

2014-06-01

Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters weremore » derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.« less

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer.

PubMed

Wu, Jiang; Zhu, Hong; Li, Kai; Wang, Xin-Gang; Gui, Yi; Lu, Guang-Ming

2014-10-01

The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18 F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18 F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18 F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18 F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUV max ) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUV max was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUV max of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of gastric lymphoma: Comparisons with gastric cancer

PubMed Central

WU, JIANG; ZHU, HONG; LI, KAI; WANG, XIN-GANG; GUI, YI; LU, GUANG-MING

2014-01-01

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in numerous malignant tumors, including gastric lymphoma, is well-established. However, there have been few studies with regard to the 18F-FDG PET/CT features of gastric lymphoma. The aim of the present study was to characterize the 18F-FDG PET/CT features of gastric lymphoma, which were compared with those of gastric cancer. Prior to treatment, 18F-FDG PET/CT was performed on 24 patients with gastric lymphoma and 43 patients with gastric cancer. The 18F-FDG PET/CT pattern of gastric wall lesions was classified as one of three types: Type I, diffuse thickening of the gastric wall with increased FDG uptake infiltrating more than one-third of the total stomach; type II, segmental thickening of the gastric wall with elevated FDG uptake involving less than one-third of the total stomach; and type III, local thickening of the gastric wall with focal FDG uptake. The incidence of the involvement of more than one region of the stomach was higher in the patients with gastric lymphoma than in those with gastric cancer. Gastric FDG uptake was demonstrated in 23 of the 24 patients (95.8%) with gastric lymphoma and in 40 of the 43 patients (93.0%) with gastric cancer. Gastric lymphoma predominantly presented with type I and II lesions, whereas gastric cancer mainly presented with type II and III lesions. The maximal thickness was larger and the maximal standard uptake value (SUVmax) was higher in the patients with gastric lymphoma compared with those with gastric cancer. A positive correlation between the maximal thickness and SUVmax was confirmed for the gastric cancer lesions, but not for the gastric lymphoma lesions. There was no difference in the maximal thickness and SUVmax of the gastric wall lesions between the patients without and with extragastric involvement, for gastric lymphoma and gastric cancer. Overall, certain differences exist in the findings between gastric

Textural features of 18F-fluorodeoxyglucose positron emission tomography scanning in diagnosing aortic prosthetic graft infection.

PubMed

Saleem, Ben R; Beukinga, Roelof J; Boellaard, Ronald; Glaudemans, Andor W J M; Reijnen, Michel M P J; Zeebregts, Clark J; Slart, Riemer H J A

2017-05-01

The clinical problem in suspected aortoiliac graft infection (AGI) is to obtain proof of infection. Although 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography scanning (PET) has been suggested to play a pivotal role, an evidence-based interpretation is lacking. The objective of this retrospective study was to examine the feasibility and utility of 18 F-FDG uptake heterogeneity characterized by textural features to diagnose AGI. Thirty patients with a history of aortic graft reconstruction who underwent 18 F-FDG PET/CT scanning were included. Sixteen patients were suspected to have an AGI (group I). AGI was considered proven only in the case of a positive bacterial culture. Positive cultures were found in 10 of the 16 patients (group Ia), and in the other six patients, cultures remained negative (group Ib). A control group was formed of 14 patients undergoing 18 F-FDG PET for other reasons (group II). PET images were assessed using conventional maximal standardized uptake value (SUVmax), tissue-to-background ratio (TBR), and visual grading scale (VGS). Additionally, 64 different 18 F-FDG PET based textural features were applied to characterize 18 F-FDG uptake heterogeneity. To select candidate predictors, univariable logistic regression analysis was performed (α = 0.16). The accuracy was satisfactory in case of an AUC > 0.8. The feature selection process yielded the textural features named variance (AUC = 0.88), high grey level zone emphasis (AUC = 0.87), small zone low grey level emphasis (AUC = 0.80), and small zone high grey level emphasis (AUC = 0.81) most optimal for distinguishing between groups I and II. SUVmax, TBR, and VGS were also able to distinguish between these groups with AUCs of 0.87, 0.78, and 0.90, respectively. The textural feature named short run high grey level emphasis was able to distinguish group Ia from Ib (AUC = 0.83), while for the same task the TBR and VGS were not found to be predictive. SUVmax

Computed tomography and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography findings in adrenal candidiasis and histoplasmosis: two cases.

PubMed

Altinmakas, Emre; Guo, Ming; Kundu, Uma R; Habra, Mouhammed Amir; Ng, Chaan

2015-01-01

We report the contrast-enhanced computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography findings in adrenal histoplasmosis and candidiasis. Both demonstrated bilateral hypermetabolic heterogeneous adrenal masses with limited wash-out on delayed CT. Adrenal candidiasis has not been previously reported, nor have the CT wash-out findings in either infection. The adrenal imaging findings are indistinguishable from malignancy, which is more common; but in this setting, physicians should be alert to the differential diagnosis of fungal infections, since it can be equally deadly. Published by Elsevier Inc.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma.

PubMed

Li, Xiao-Feng; Fu, Qiang; Dong, You-Wen; Liu, Jian-Jing; Song, Xiu-Yu; Dai, Dong; Zuo, Cong; Xu, Wen-Gui

2016-09-14

To compare (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent (18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by χ(2) test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 ± 9.24 vs 8.35 ± 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 ± 4.02 vs 4.88 ± 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma

PubMed Central

Li, Xiao-Feng; Fu, Qiang; Dong, You-Wen; Liu, Jian-Jing; Song, Xiu-Yu; Dai, Dong; Zuo, Cong; Xu, Wen-Gui

2016-01-01

AIM To compare 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. METHODS Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent 18F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by χ2 test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 ± 9.24 vs 8.35 ± 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 ± 4.02 vs 4.88 ± 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. CONCLUSION PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma. PMID:27678362

High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease.

PubMed

Chittiboina, Prashant; Montgomery, Blake K; Millo, Corina; Herscovitch, Peter; Lonser, Russell R

2015-04-01

OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of(18)F-fluorodeoxyglucose ((18)F-FDG). To determine the sensitivity of this imaging modality, the authors compared(18)F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD). METHODS Consecutive patients with CD who underwent preoperative(18)F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11-59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.(18)F-FDG hrPET demonstrated increased(18)F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3-14 mm). Maximum SUV was significantly higher for(18)F-FDG hrPET-positive tumors (difference = 5.1, 95% CI 2.1-8.1; p = 0.004) than for(18)F-FDG hrPET-negative tumors.(18)F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with(18)F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All(18)F-FDG hrPET-positive adenomas had a less than a 180% ACTH increase and(18)F-FDG hrPET-negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by(18)F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on(18)F-FDG hrPET. CONCLUSIONS While(18)F-FDG hrPET imaging can

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

PubMed

Madsen, Karine; Hesby, Sara; Poulsen, Ingrid; Fuglsang, Stefan; Graff, Jesper; Larsen, Karen B; Kammersgaard, Lars P; Law, Ian; Siebner, Hartwig R

2017-11-01

Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [ 18 F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [ 18 F]FDG-PET scan and venous blood sampling. Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. Our study demonstrates that the analysis method of the [ 18 F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. We recommend supplementing a static [ 18 F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc. Copyright © 2017 Elsevier B.V. All rights reserved.

(18)F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Liao, Zhongxing; Gomez, Daniel R; Stingo, Francesco; Mohan, Radhe; Martel, Mary K; Briere, Tina M; Court, Laurence E

2016-11-01

We sought to investigate the ability of mid-treatment (18)F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized (18)F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion. Symptom progression was predicted with an AUC of 0

Verbal fluency in research conducted with PET technique under conditions of extended cognitive activation with the use of 18F-fluorodeoxyglucose (FDG) tracer.

PubMed

Zając-Lamparska, Ludmiła; Wiłkość, Monika; Markowska, Anita; Laskowska-Levy, Ilona Paulina; Wróbel, Marek; Małkowski, Bogdan

2017-08-29

Functional neuroimaging of the brain is a widely used method to study cognitive functions. The aim of this study was to compare the activity of the brain during performance of the tasks of phonemic and semantic fluency with the paced-overt technique in terms of prolonged activation of the brain. The study included 17 patients aged 20-40 years who were treated in the past for Hodgkin'slymphoma, now in remission. Due to the type of task, the subjectswere divided into two groups. Nine people performed the phonemic fluency task, and eight semantic. Due to the disease, all subjects were subject to neuropsychological diagnosis. The diagnosis of any cognitive impairment was an exclusion criterion. Neuroimaging was performed using PET technique with 18F-fluorodeoxyglucose (FDG) tracer. Performance of a verbal fluency test, regardless of the version of the task, was associated with greater activity of the left hemisphere of the brain. The most involved areas compared with other areas of key importance for the performance of verbal fluency tasks were frontal lobes. An increased activity of parietal structures was also shown. The study did not reveal differences in brain activity depending on the type of task. Performing the test in both phonemic and semantic form for a long time, in terms of increased cognitive control resulting from the test procedure, could result in significant advantage of prefrontal lobe activityin both types of tasks and made it impossible to observe the processes specific to each of them.

Accuracy of 18F-FDOPA Positron Emission Tomography and 18F-FET Positron Emission Tomography for Differentiating Radiation Necrosis from Brain Tumor Recurrence.

PubMed

Yu, Jun; Zheng, Jingwei; Xu, Weilin; Weng, Jiaqi; Gao, Liansheng; Tao, Li; Liang, Feng; Zhang, Jianmin

2018-06-01

Distinguishing radiation necrosis from brain tumor recurrence remains challenging. We performed a meta-analysis to assess the diagnostic accuracy of 2 different amino acid tracers used in positron emission tomography/computed tomography scans: 18 F-FDOPA (6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine) and 18 F-FET (O-(2-18F-fluoroethyl)-L-tyrosine). We searched for studies in 3 databases: PubMed, Embase, and Chinese Biomedical databases. The data were extracted from eligible studies and then processed with heterogeneity test, threshold effect test, and calculations of sensitivity, specificity, and area under the summary receiver operating characteristic curve. Meta-regression and subgroup analyses were performed to explore the source of heterogeneity. A total of 48 studies ( 18 F-FDOPA, n = 21; 18 F-FET, n = 27) were included. Quantitative synthesis determined pooled weight values in the 18 F-FDOPA and 18 F-FET groups: sensitivity, 0.85 versus 0.82; specificity, 0.77 versus 0.80; diagnostic odds ratio, 21.7 versus 23.03; area under the curve (AUC) values, 0.8771 versus 0.8976 (P = 0.46). Moreover, the type of tumor was identified as the possible source of the significant heterogeneity (I 2  = 52%; P = 0.003) found in the 18 F-FDOPA group. In meta-regression and subgroup analyses, 18 F-FDOPA showed better diagnostic accuracy in patients with glioma compared with patients with brain metastases (AUC values, 0.9691 vs. 0.837; P < 0.01). 18 F-FDOPA also showed a significant advantage in the diagnosis of glioma recurrence compared with 18 F-FET (AUC values, 0.9691 vs. 0.9124; P = 0.015). Both 18 F-FDOPA and 18 F-FET exhibit moderate overall accuracy in diagnosing brain tumor recurrence from radiation necrosis. However, 18 F-FDOPA is more adept at diagnosing glioma recurrence compared with brain metastases, and it is more effective than 18 F-FET in diagnosing glioma recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2015-09-01

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

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

PubMed Central

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

2015-01-01

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

Correlation Between Infection Status of Epstein-Barr Virus and 18F-Fluorodeoxyglucose Uptake in Patients with Advanced Gastric Cancer.

PubMed

Na, Sae Jung; Park, Hye Lim; O, Joo Hyun; Lee, Sung Yong; Song, Kyo Young; Kim, Sung Hoon

2017-01-01

Epstein-Barr virus-associated gastric cancer (EBVaGC) is one of the four molecular subtypes of gastric cancer, as defined by the classification recently proposed by The Cancer Genome Atlas. We evaluated the correlation between EBV positivity and 18 F-fluorodeoxyglucose ( 18 F-FDG) uptake by positron emission tomography/computed tomography (PET/CT) in patients with gastric cancer. We retrospectively enrolled patients with gastric cancer who underwent pretreatment 18 F-FDG PET/CT and subsequent surgical resection, and then were diagnosed with advanced gastric cancer (pathologic stage ≥T2 with any N stage). Maximum standardized uptake values (SUV max ) of gastric cancer were measured by pretreatment 18 F-FDG PET/CT. EBV sequences were detected by in situ hybridization (ISH) techniques. We analyzed the correlation between EBV positivity, clinicopathologic features and metabolic activity of the primary tumor. A total of 205 patients were included and 15 (7.3%) patients were identified as having EBV-positive gastric cancer. Age, gender, tumor location, and histological type showed no significant differences between EBV-positive and negative groups. EBV-positive cancer is significantly more frequent in the higher-metabolic-tumor group than in the lower one (p=0.032). The mean SUV max of gastric cancers showed significant differences between EBV-positive and negative groups (9.9±4.2 vs. 7.0±4.8, p=0.026). The infection status of EBV was significantly related to the 18 F-FDG uptake of primary tumors in patients with advanced gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

2017-06-15

N-(2-[ 18 F]Fluoropropionyl)-l-glutamic acid ([ 18 F]FPGLU) is a potential amino acid tracer for tumor imaging with positron emission tomography. However, due to the complicated multistep synthesis, the routine production of [ 18 F]FPGLU presents many challenging laboratory requirements. To simplify the synthesis process of this interesting radiopharmaceutical, an efficient automated synthesis of [ 18 F]FPGLU was performed on a modified commercial fluorodeoxyglucose synthesizer via a 2-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 minutes. 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 minutes. Moreover, all these results were achieved using the similar on-column hydrolysis procedure on the modified fluorodeoxyglucose synthesis module. Copyright © 2017 John Wiley & Sons, Ltd.

18F-fluorodeoxyglucose imaging of primary malignant pericardial mesothelioma with concurrent pericardial and pleural effusions and bone metastasis: A case report.

PubMed

Li, Xiaohui; Lu, Rugang; Zhao, Youcai; Wang, Feng; Shao, Guoqiang

2018-06-01

Primary malignant pericardial mesothelioma (PMPM) is an aggressive tumor that originates from the mesothelial cells of the pericardium. PMPM with extensive atrial infiltration and bone metastasis is extremely rare. The diagnosis and staging of PMPM based on anatomical imaging may be difficult when concurrent pericardial and pleural effusions are present. A 28-year-old man presented with progressive chest pain. Concurrent pericardial and pleural effusions were identified on computed tomography. On echocardiography, mild thickening and adhesions of the pericardium with the right ventricle and atrium were observed. 18 F-fluorodeoxyglucose (FDG) metabolism imaging revealed increased accumulation in the pericardium and adjacent right atrium. Ring-shaped radioactivity aggregation and bone destruction in the sacrum were demonstrated on 18 F-FDG and 99m Tc-methyl diphosphonate imaging. The diagnosis of PMPM was subsequently confirmed by pathology. The patient survived for >1.5 years with comprehensive treatment.

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

PubMed

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

2001-04-01

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

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

PubMed

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

2017-08-01

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

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

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

Kang, Jiayin; Gao, Yaozong; Shi, Feng

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

Comparison of whole body magnetic resonance imaging (WBMRI) to whole body computed tomography (WBCT) or 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) in patients with myeloma: Systematic review of diagnostic performance.

PubMed

Gariani, Joanna; Westerland, Olwen; Natas, Sarah; Verma, Hema; Cook, Gary; Goh, Vicky

2018-04-01

To undertake a systematic review to determine the diagnostic performance of whole body MRI (WBMRI) including diffusion weighted sequences (DWI) compared to whole body computed tomography (WBCT) or 18 F-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG PET/CT) in patients with myeloma. Two researchers searched the primary literature independently for WBMRI studies of myeloma. Data were extracted focusing on the diagnostic ability of WBMRI versus WBCT and 18 F-FDG PET/CT. Meta-analysis was intended. 6 of 2857 articles were eligible that included 147 patients, published from 2008 to 2016. Studies were heterogeneous including both newly diagnosed & relapsed patients. All were single centre studies. Four of the six studies (66.7%) accrued prospectively and 5/6 (83.3%, 3 prospective) included WBMRI and 18 F-FDG PET/CT. Three of seven (42.9%) included DWI. The lack of an independent reference standard for individual lesions was noted in 5/6 (83.3%) studies. Studies reported that WBMRI detected more lesions than 18 F-FDG PET/CT (sensitivity 68-100% versus 47-100%) but was less specific (specificity 37-83% versus 62-85.7%). No paper assessed impact on management. Studies were heterogeneous, the majority lacking an independent reference standard. Future prospective trials should address these limitations and assess the impact of WBMRI on management. Copyright © 2018. Published by Elsevier B.V.

Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Study.

PubMed

Singh, Parmanand; Emami, Hamed; Subramanian, Sharath; Maurovich-Horvat, Pal; Marincheva-Savcheva, Gergana; Medina, Hector M; Abdelbaky, Amr; Alon, Achilles; Shankar, Sudha S; Rudd, James H F; Fayad, Zahi A; Hoffmann, Udo; Tawakol, Ahmed

2016-12-01

Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM. In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwent 18 F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and after 12 weeks of treatment with atorvastatin. Coronary arterial inflammation ( 18 F-fluorodeoxyglucose uptake, expressed as target-to-background ratio) was assessed in the left main coronary artery (LMCA). While blinded to the PET findings, contrast-enhanced computed tomographic angiography was performed to characterize the presence of HRM (defined as noncalcified or partially calcified plaques) in the LMCA. Arterial inflammation (target-to-background ratio) was higher in LMCA segments with HRM than those without HRM (mean±SEM: 1.95±0.43 versus 1.67±0.32 for LMCA with versus without HRM, respectively; P=0.04). Moreover, atorvastatin treatment for 12 weeks reduced target-to-background ratio more in LMCA segments with HRM than those without HRM (12 week-baseline Δtarget-to-background ratio [95% confidence interval]: -0.18 [-0.35 to -0.004] versus 0.09 [-0.06 to 0.26]; P=0.02). Furthermore, this relationship between coronary plaque morphology and change in LMCA inflammatory activity remained significant after adjusting for baseline low-density lipoprotein and statin dose (β=-0.27; P=0.038). In this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease. URL: http://www.clinicaltrials.gov. Unique identifier

18F-labeled norepinephrine transporter tracer [18F]NS12137: radiosynthesis and preclinical evaluation.

PubMed

Kirjavainen, Anna K; Forsback, Sarita; López-Picón, Francisco R; Marjamäki, Päivi; Takkinen, Jatta; Haaparanta-Solin, Merja; Peters, Dan; Solin, Olof

2018-01-01

Several psychiatric and neurodegenerative diseases are associated with malfunction of brain norepinephrine transporter (NET). However, current clinical evaluations of NET function are limited by the lack of sufficiently sensitive methods of detection. To this end, we have synthesized exo-3-[(6-[ 18 F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.2.1]-octane ([ 18 F]NS12137) as a radiotracer for positron emission tomography (PET) and have demonstrated that it is highly specific for in vivo detection of NET-rich regions of rat brain tissue. We applied two methods of electrophilic, aromatic radiofluorination of the precursor molecule, exo-3-[(6-trimethylstannyl-2-pyridyl)oxy]-8-azabicyclo-[3.2.1]octane-8-carboxylate: (1) direct labeling with [ 18 F]F 2 , and (2) labeling with [ 18 F]Selectfluor, a derivative of [ 18 F]F 2 , using post-target produced [ 18 F]F 2 . The time-dependent distribution of [ 18 F]NS12137 in brain tissue of healthy, adult Sprague-Dawley rats was determined by ex vivo autoradiography. The specificity of [ 18 F]NS12137 binding was demonstrated on the basis of competitive binding by nisoxetine, a known NET antagonist of high specificity. [ 18 F]NS12137 was successfully synthesized with radiochemical yields of 3.9% ± 0.3% when labeled with [ 18 F]F 2 and 10.2% ± 2.7% when labeled with [ 18 F]Selectfluor. The molar activity of radiotracer was 8.8 ± 0.7 GBq/μmol with [ 18 F]F 2 labeling and 6.9 ± 0.4 GBq/μmol with [ 18 F]Selectfluor labeling at the end of synthesis of [ 18 F]NS12137. Uptake of [ 18 F]NS12137 in NET-rich areas in rat brain was demonstrated with the locus coeruleus (LCoe) having the highest regional uptake. Prior treatment of rats with nisoxetine showed no detectable [ 18 F]NS12137 in the LCoe. Analyses of whole brain samples for radiometabolites showed only the parent compound [ 18 F]NS12137. Uptake of 18 F-radioactivity in bone increased with time. The two electrophilic 18 F-labeling methods proved to be suitable for synthesis of [ 18 F

Pulmonary suture abscess with false-positive 18F-fluorodeoxyglucose positron emission scan mimicking lung cancer recurrence.

PubMed

Iwasaki, Teruo; Nakagawa, Katsuhiro; Katsura, Hiroshi; Nakane, Shigeru; Kawahara, Kunimitsu; Fukuda, Haruyuki

2006-08-01

We present the case of a 57-year-old woman with pulmonary suture abscess. She had undergone right S3 segmentectomy for early lung adenocarcinoma 7 years before and right breast-conserving surgery for invasive ductal carcinoma 5 months previously, followed by irradiation plus endocrine therapy. Chest radiography and computed tomography revealed an irregular mass (3.5 cm in diameter) between the residual S1 segment and the middle lobe, neighboring the staple line of the segmentectomy. 18F-fluorodeoxyglucose uptake into the mass increased, seen by positron emission scans. Therefore, we could not rule out the possibility of local recurrence of lung cancer and resected it. Pathologically and microbiologically, the mass was a suture abscess arising around the nylon suture of the previous segmentectomy. This lesion was the result of a foreign-body reaction, as confirmed by polarized microscopy. Moreover, titanium staples at the segmentectomy and breast-conserving surgery may also have contributed to this condition.

Effects of hyperglycemia on fluorine-18-fluorodeoxyglucose biodistribution in a large oncology clinical practice.

PubMed

Rosica, Dillenia; Cheng, Su-Chun; Hudson, Margo; Sakellis, Christopher; Van den Abbeele, Annick D; Kim, Chun K; Jacene, Heather A

2018-05-01

Suggested cutoff points of blood glucose levels (BGL) before F-FDG PET/CT scanning vary between 120 and 200 mg/dl in current guidelines. This study's purpose was to compare the frequency of abnormal fluorine-18-fluorodeoxyglucose (F-FDG) biodistribution on PET/CT scans of patients with various ranges of abnormal BGL and to determine the effect of BGL greater than 200 mg/dl on F-FDG uptake in various organs. F-FDG PET/CT scans were retrospectively reviewed for 325 patients with BGL greater than 120 mg/dl at the time of scan and 112 with BGL less than or equal to 120 mg/dl. F-FDG biodistribution was categorized as normal, mildly abnormal, or abnormal by visual analysis of brain, background soft tissue, and muscle. Mean standardized uptake values (SUVmean) in brain, liver, fat (flank), gluteal muscle, and blood pool (aorta) were recorded. F-FDG biodistribution frequencies were assessed using a nonparametric χ-test for trend. Normal organ SUVs were compared using Kruskal-Wallis tests using the following BGL groupings: ≤120, 121-150, 151-200, and ≥201 mg/dl. Although higher BGL were significantly associated with an increased proportion of abnormal biodistribution (P<0.001), most patients with BGL less than or equal to 200 mg/dl had normal or mildly abnormal biodistribution. Average brain SUVmean significantly decreased with higher BGL groupings (P<0.001). Average aorta, gluteal muscle, and liver SUVmean did not significantly differ among groups with BGL greater than 120 mg/dl (P=0.66, 0.84, and 0.39, respectively), but were significantly lower in those with BGL less than or equal to 120 mg/dl (P≤0.001). Flank fat SUVmean was not significantly different among BGL groups (P=0.67). Abnormal F-FDG biodistribution is associated with higher BGL at the time of scan, but the effects are negligible or mild in most patients with BGL less than 200 mg/dl. Although mildly increased soft tissue uptake is seen with BGL greater than 120 mg/dl, decline in

Clinical experience with (18)F-fluorodeoxyglucose positron emission tomography and (123)I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients.

PubMed

Gil, Tae Young; Lee, Do Kyung; Lee, Jung Min; Yoo, Eun Sun; Ryu, Kyung-Ha

2014-06-01

To evaluate the potential utility of (123)I-metaiodobenzylguanine ((123)I-MIBG) scintigraphy and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) for the detection of primary and metastatic lesions in pediatric neuroblastoma (NBL) patients, and to determine whether (18)F-FDG PET is as beneficial as (123)I-MIBG imaging. We selected 8 NBL patients with significant residual mass after operation and who had paired (123)I-MIBG and (18)F-FDG PET images that were obtained during the follow-up. We retrospectively reviewed the clinical charts and the findings of 45 paired scans. Both scans correlated relatively well with the disease status as determined by standard imaging modalities during follow-up; the overall concordance rates were 32/45 (71.1%) for primary tumor sites and 33/45 (73.3%) for bone-bone marrow (BM) metastatic sites. In detecting primary tumor sites, (123)I-MIBG might be superior to (18)F-FDG PET. The sensitivity of (123)I-MIBG and (18)F-FDG PET were 96.7% and 70.9%, respectively, and their specificity were 85.7% and 92.8%, respectively. (18)F-FDG PET failed to detect 9 true NBL lesions in 45 follow-up scans (false negative rate, 29%) with positive (123)I-MIBG. For bone-BM metastatic sites, the sensitivity of (123)I-MIBG and (18)F-FDG PET were 72.7% and 81.8%, respectively, and the specificity were 79.1% and 100%, respectively. (123)I-MIBG scan showed higher false positivity (20.8%) than (18)F-FDG PET (0%). (123)I-MIBG is superior for delineating primary tumor sites, and (18)F-FDG PET could aid in discriminating inconclusive findings on bony metastatic NBL. Both scans can be complementarily used to clearly determine discrepancies or inconclusive findings on primary or bone-BM metastatic NBL during follow-up.

Simultaneous whole body 18F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with 18F-fluorodeoxyglucose positron emission tomography computed tomography

PubMed Central

Pugmire, Brian S; Guimaraes, Alexander R; Lim, Ruth; Friedmann, Alison M; Huang, Mary; Ebb, David; Weinstein, Howard; Catalano, Onofrio A; Mahmood, Umar; Catana, Ciprian; Gee, Michael S

2016-01-01

AIM: To describe our preliminary experience with simultaneous whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients. METHODS: This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated 18F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard. RESULTS: A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was

Simultaneous whole body (18)F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging for evaluation of pediatric cancer: Preliminary experience and comparison with (18)F-fluorodeoxyglucose positron emission tomography computed tomography.

PubMed

Pugmire, Brian S; Guimaraes, Alexander R; Lim, Ruth; Friedmann, Alison M; Huang, Mary; Ebb, David; Weinstein, Howard; Catalano, Onofrio A; Mahmood, Umar; Catana, Ciprian; Gee, Michael S

2016-03-28

To describe our preliminary experience with simultaneous whole body (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and magnetic resonance imaging (PET-MRI) in the evaluation of pediatric oncology patients. This prospective, observational, single-center study was Health Insurance Portability and Accountability Act-compliant, and institutional review board approved. To be eligible, a patient was required to: (1) have a known or suspected cancer diagnosis; (2) be under the care of a pediatric hematologist/oncologist; and (3) be scheduled for clinically indicated (18)F-FDG positron emission tomography-computed tomography (PET-CT) examination at our institution. Patients underwent PET-CT followed by PET-MRI on the same day. PET-CT examinations were performed using standard department protocols. PET-MRI studies were acquired with an integrated 3 Tesla PET-MRI scanner using whole body T1 Dixon, T2 HASTE, EPI diffusion-weighted imaging (DWI) and STIR sequences. No additional radiotracer was given for the PET-MRI examination. Both PET-CT and PET-MRI examinations were reviewed by consensus by two study personnel. Test performance characteristics of PET-MRI, for the detection of malignant lesions, including FDG maximum standardized uptake value (SUVmax) and minimum apparent diffusion coefficient (ADCmin), were calculated on a per lesion basis using PET-CT as a reference standard. A total of 10 whole body PET-MRI exams were performed in 7 pediatric oncology patients. The mean patient age was 16.1 years (range 12-19 years) including 6 males and 1 female. A total of 20 malignant and 21 benign lesions were identified on PET-CT. PET-MRI SUVmax had excellent correlation with PET-CT SUVmax for both benign and malignant lesions (R = 0.93). PET-MRI SUVmax > 2.5 had 100% accuracy for discriminating benign from malignant lesions using PET-CT reference. Whole body DWI was also evaluated: the mean ADCmin of malignant lesions (780.2 + 326.6) was significantly lower than

Single-Cell Analysis of [18F]Fluorodeoxyglucose Uptake by Droplet Radiofluidics.

PubMed

Türkcan, Silvan; Nguyen, Julia; Vilalta, Marta; Shen, Bin; Chin, Frederick T; Pratx, Guillem; Abbyad, Paul

2015-07-07

Radiolabels can be used to detect small biomolecules with high sensitivity and specificity without interfering with the biochemical activity of the labeled molecule. For instance, the radiolabeled glucose analogue, [18F]fluorodeoxyglucose (FDG), is routinely used in positron emission tomography (PET) scans for cancer diagnosis, staging, and monitoring. However, despite their widespread usage, conventional radionuclide techniques are unable to measure the variability and modulation of FDG uptake in single cells. We present here a novel microfluidic technique, dubbed droplet radiofluidics, that can measure radiotracer uptake for single cells encapsulated into an array of microdroplets. The advantages of this approach are multiple. First, droplets can be quickly and easily positioned in a predetermined pattern for optimal imaging throughput. Second, droplet encapsulation reduces cell efflux as a confounding factor, because any effluxed radionuclide is trapped in the droplet. Last, multiplexed measurements can be performed using fluorescent labels. In this new approach, intracellular radiotracers are imaged on a conventional fluorescence microscope by capturing individual flashes of visible light that are produced as individual positrons, emitted during radioactive decay, traverse a scintillator plate placed below the cells. This method is used to measure the cell-to-cell heterogeneity in the uptake of tracers such as FDG in cell lines and cultured primary cells. The capacity of the platform to perform multiplexed measurements was demonstrated by measuring differential FDG uptake in single cells subjected to different incubation conditions and expressing different types of glucose transporters. This method opens many new avenues of research in basic cell biology and human disease by capturing the full range of stochastic variations in highly heterogeneous cell populations in a repeatable and high-throughput manner.

{sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Can Quantify and Predict Esophageal Injury During Radiation Therapy

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

Niedzielski, Joshua S., E-mail: jsniedzielski@mdanderson.org; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas; Yang, Jinzhong

Purpose: We sought to investigate the ability of mid-treatment {sup 18}F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. Methods and Materials: This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized {sup 18}F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We usedmore » nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. Results: Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PubMed

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Brain uptake of a non-radioactive pseudo-carrier and its effect on the biodistribution of [(18)F]AV-133 in mouse brain.

PubMed

Wu, Xianying; Zhou, Xue; Zhang, Shuxian; Zhang, Yan; Deng, Aifang; Han, Jie; Zhu, Lin; Kung, Hank F; Qiao, Jinping

2015-07-01

9-[(18)F]Fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133) is a new PET imaging agent targeting vesicular monoamine transporter type II (VMAT2). To shorten the preparation of [(18)F]AV-133 and to make it more widely available, a simple and rapid purification method using solid-phase extraction (SPE) instead of high-pressure liquid chromatography (HPLC) was developed. The SPE method produced doses containing the non-radioactive pseudo-carrier 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). The objectives of this study were to evaluate the brain uptake of AV-149 by UPLC-MS/MS and its effect on the biodistribution of [(18)F]AV-133 in the brains of mice. The mice were injected with a bolus including [(18)F]AV-133 and different doses of AV-149. Brain tissue and blood samples were harvested. The effect of different amounts of AV-149 on [(18)F]AV-133 was evaluated by quantifying the brain distribution of radiolabelled tracer [(18)F]AV-133. The concentrations of AV-149 in the brain and plasma were analyzed using a UPLC-MS/MS method. The concentrations of AV-149 in the brain and plasma exhibited a good linear relationship with the doses. The receptor occupancy curve was fit, and the calculated ED50 value was 8.165mg/kg. The brain biodistribution and regional selectivity of [(18)F]AV-133 had no obvious differences at AV-149 doses lower than 0.1mg/kg. With increasing doses of AV-149, the brain biodistribution of [(18)F]AV-133 changed significantly. The results are important to further support that the improved radiolabelling procedure of [(18)F]AV-133 using an SPE method may be suitable for routine clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2007-10-01

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

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

[Solitary Peripheral Pulmonary Squamous Cell Papilloma;Diagnostic Significance of 18F-fluorodeoxyglucose Positron Emission Tomography Findings].

PubMed

Hayashi, Tetsuya; Tachibana, Syuichi; Nakao, Keiichi; Tokitsu, Kosuke; Morita, Takuya; Kishima, Genichi

2017-04-01

The patient was a 79-year-old woman who had received enucleation of right pulmonary papilloma 7 years earlier. She experienced bloody sputum and was therefore referred to our hospital. Chest computed tomography revealed a mass shadow(21 mm) in the right upper lobe (S2). By bronchoscopy, there was no bulging lesion in the visible range. SCC and CEA increased to 6.4 ng/ml and 6.42 ng/ml, respectively. Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the region of the right-lung mass shadow (maximum standardized uptake value 12.95). Since malignancy could not be ruled out, a wedge resection was performed. The post-operative histopathologic diagnosis was squamous cell papilloma. Our literature review showed 12 out of 14 cases with solitary papilloma of the peripheral lung to have increased FDG uptake. Ki-67 positive cells were confirmed in the basal layers of the epithelium, and active cell proliferation of the papilloma is likely to be a cause of increased FDG uptake.

Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment.

PubMed

Verger, Antoine; Stoffels, Gabriele; Galldiks, Norbert; Lohmann, Philipp; Willuweit, Antje; Neumaier, Bernd; Geisler, Stefanie; Langen, Karl-Josef

2018-04-23

Cis-4-[ 18 F]fluoro-D-proline (D-cis-[ 18 F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[ 18 F]FPro in human brain tumors after multimodal treatment. In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[ 18 F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBR mean , LBR max ), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [ 18 F]FET PET (n = 10). D-cis-[ 18 F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBR mean 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBR max 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[ 18 F]FPro uptake. Distribution of [ 18 F]FET and D-cis-[ 18 F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different. The high accumulation of D-cis-[ 18 F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[ 18 F]FPro for treatment monitoring.

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

PubMed

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

2016-09-01

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

Cellular Origin of [18F]FDG-PET Imaging Signals During Ceftriaxone-Stimulated Glutamate Uptake: Astrocytes and Neurons.

PubMed

Dienel, Gerald A; Behar, Kevin L; Rothman, Douglas L

2017-12-01

Ceftriaxone stimulates astrocytic uptake of the excitatory neurotransmitter glutamate, and it is used to treat glutamatergic excitotoxicity that becomes manifest during many brain diseases. Ceftriaxone-stimulated glutamate transport was reported to drive signals underlying [ 18 F]fluorodeoxyglucose-positron emission tomographic ([ 18 F]FDG-PET) metabolic images of brain glucose utilization and interpreted as supportive of the notion of lactate shuttling from astrocytes to neurons. This study draws attention to critical roles of astrocytes in the energetics and imaging of brain activity, but the results are provocative because (1) the method does not have cellular resolution or provide information about downstream pathways of glucose metabolism, (2) neuronal and astrocytic [ 18 F]FDG uptake were not separately measured, and (3) strong evidence against lactate shuttling was not discussed. Evaluation of potential metabolic responses to ceftriaxone suggests lack of astrocytic specificity and significant contributions by pre- and postsynaptic neuronal compartments. Indeed, astrocytic glycolysis may not make a strong contribution to the [ 18 F]FDG-PET signal because partial or complete oxidation of one glutamate molecule on its uptake generates enough ATP to fuel uptake of 3 to 10 more glutamate molecules, diminishing reliance on glycolysis. The influence of ceftriaxone on energetics of glutamate-glutamine cycling must be determined in astrocytes and neurons to elucidate its roles in excitotoxicity treatment.

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

PubMed

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

2015-01-01

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

GMP-compliant automated synthesis of [(18)F]AV-45 (Florbetapir F 18) for imaging beta-amyloid plaques in human brain.

PubMed

Yao, Cheng-Hsiang; Lin, Kun-Ju; Weng, Chi-Chang; Hsiao, Ing-Tsung; Ting, Yi-Shu; Yen, Tzu-Chen; Jan, Tong-Rong; Skovronsky, Daniel; Kung, Mei-Ping; Wey, Shiaw-Pyng

2010-12-01

We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of (18)F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of beta-amyloid (Abeta) plaques in the brain of Alzheimer's disease patients. [(18)F]AV-45 was prepared in 105 min using a tosylate precursor with Sumitomo modules for radiosynthesis under GMP-compliant conditions. The overall yield was 25.4+/-7.7% with a final radiochemical purity of 95.3+/-2.2% (n=19). The specific activity of [(18)F]AV-45 reached as high as 470+/-135 TBq/mmol (n=19). The present studies show that [(18)F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use. Copyright 2010 Elsevier Ltd. All rights reserved.

Clinical importance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography in the management of patients with bronchoalveolar carcinoma: Role in the detection of recurrence.

PubMed

Skoura, Evangelia; Datseris, Ioannis E; Exarhos, Dimitrios; Chatziioannou, Sophia; Oikonomopoulos, Georgios; Samartzis, Alexandros; Giannopoulou, Chariklia; Syrigos, Konstantinos N

2013-05-01

[ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been reported to have a low sensitivity in the initial diagnosis of bronchoalveolar carcinoma (BAC) due to BAC's low metabolic activity. The aim of this study was to assess the value of [ 18 F]FDG-PET/CT in the detection of BAC recurrence. Between February 2007 and September 2011, the [ 18 F]FDG-PET/CT scans that were performed on patients with known, histologically proven BAC were studied. A total of 24 [ 18 F]FDG-PET/CT scans were performed in 22 patients, including 16 males and 6 females, with a mean age of 65±9 years. Among the scans, 15 were performed to assess for possible recurrence with equivocal findings in conventional imaging methods and 9 for restaging post-therapy. In all cases conventional imaging studies (CT and MRI) were performed 5-30 days prior to PET/CT. Among the 24 [ 18 F]FDG-PET/CT scans, 18 were positive and 6 negative. Among the 15 [ 18 F]FDG-PET/CT scans performed for suspected recurrence, 34 lesions were detected and the mean maximum standardized uptake value (SUVmax) was 6.8±3.26. In nine scans, upstaging was observed, while two were in agreement with the findings of the conventional modalities. A greater number of lesions were detected in two scans and fewer lesions were detected in one, with no change in staging. Only one scan was negative. By contrast, in patients examined for restaging, there were only five lesions with a mean SUVmax of 4.86±3.18. Agreement between the findings of [ 18 F]FDG-PET/CT and the conventional modalities was observed in 8 out of 9 cases. Although [ 18 F]FDG-PET/CT has been reported to have a low sensitivity in the initial diagnosis of BAC, the present results indicate that when there is recurrence, the lesions become [ 18 F]FDG avid. [ 18 F]FDG-PET/CT may provide further information in patients evaluated for recurrence and thus improve patient management.

In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of serotonin 4 receptors in brain.

PubMed

Tavares, Adriana Alexandre S; Caillé, Fabien; Barret, Olivier; Papin, Caroline; Lee, Hsiaoju; Morley, Thomas J; Fowles, Krista; Holden, Daniel; Seibyl, John P; Alagille, David; Tamagnan, Gilles D

2014-05-01

Serotonin 4 receptors (5-hydroxytryptamine receptor 4 [5HT4R]) hold promise as a novel therapeutic approach to multiple brain disorders, including Alzheimer and Huntington disease. In vivo imaging of these receptors with selective 5HT4R radiotracers and PET would be valuable to investigate alterations in 5HT4R in different brain disorders and to assist drug discovery. In this study, (18)F-MNI698 was evaluated as a potential PET radiotracer for imaging of 5HT4R in the brain. Eighteen PET studies were performed in 3 adult rhesus monkeys. The radiotracer was administered as a bolus intravenous injection or bolus plus constant infusion (time that would be required to inject the bolus at the infusion rate = 60 min), and arterial blood was collected for data quantification. Kinetic models were used to estimate distribution volumes and binding potentials, for which the cerebellum was used as a reference region. (18)F-MNI698 test-retest variability and upper mass dose limits were determined. Preblocking studies using several doses of SB204070, a selective 5HT4R antagonist, were performed. (18)F-MNI698 avidly entered the monkey brain (peak percentage injected dose of ∼ 6.6%), and its brain distribution was consistent with known 5HT4R densities. At 120 min after bolus injection and after the start of radiotracer infusion, only less than 5% and approximately 10% parent compound was present in blood, respectively. Measured binding potentials were underestimated by 22%-36% when noninvasive methods were used for data quantification in comparison with invasive methods. A good agreement was found between test-retest measurements. The radiotracer upper mass dose limit (<5% occupancy) was determined to be 13.1 μg per 70 kg of body weight. SB204070 blocked the radiotracer binding in a dose-dependent manner. Data indicate that (18)F-MNI698 is a promising PET radiotracer for imaging of 5HT4R in the brain, and human studies are warranted based on these study results.

Monitoring Pc 4-mediated photodynamic therapy of U87 tumors with 18F- fluorodeoxy-glucose PET imaging in the Athymic Nude Rat

NASA Astrophysics Data System (ADS)

Varghai, Davood; Cross, Nathan; Spring-Robinson, Chandra; Sharma, Rahul; Feyes, Denise K.; Ahmad, Yusra; Oleinick, Nancy L.; Muzic, Raymond F., Jr.; Dean, David

2007-02-01

Introduction: We have previously demonstrated the use of phthalocyanine Pc 4 for the photodynamic therapy (PDT) of ectopic human glial tumors in the athymic nude rat brain. We wish to determine whether 18F-fluorodeoxy-glucose ( 18F-FDG) Positron Emission Tomography (PET) imaging can detect the reduction in tumor metabolism that must occur after Pc 4-PDT-induced necrosis. Methods: 2.5 x 10 5 U87 cells were injected into the brains of 12 athymic nude rats. After 7 days of tumor growth, all 12 animals were imaged functionally by 18F-FDG micro-PET (μPET) and structurally by micro-CT and/or micro-MR. These animals received 0.5 mg/kg b.w. Pc 4 via tail-vein injection. One day later the scalp was re-incised and the tumor illuminated with 30 J/cm2 of 672-nm light from a diode laser. The next day these animals were again 18F-FDG μPET imaged. Next, the animals were euthanized and their brains were explanted for H&E histology. Results: Histology showed that tumors in the 6 Pc 4-PDT-treated animals demonstrated necrosis ranging from full to frank (severe). Preliminary analysis showed that 18F-FDG μPET activity in 3 of the 6 non-PDT group (i.e., no tumor necrosis observed) animals was seen to increase 2.28 times following tumor photoirradiation, whereas 18F-FDG μPET activity in 5 of the 6 PDT group (i.e., tumor necrosis observed) animals was seen to increase 1.15 times following tumor photoirradiation. Discussion: The increased 18F-FDG μPET activity in the PDT group was unexpected. We had expected this activity to decrease and are presently investigating the cause of this observation.

Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain.

PubMed

Ng, Kok Pin; Pascoal, Tharick A; Mathotaarachchi, Sulantha; Therriault, Joseph; Kang, Min Su; Shin, Monica; Guiot, Marie-Christine; Guo, Qi; Harada, Ryuichi; Comley, Robert A; Massarweh, Gassan; Soucy, Jean-Paul; Okamura, Nobuyuki; Gauthier, Serge; Rosa-Neto, Pedro

2017-03-31

18 F-THK5351 is a quinoline-derived tau imaging agent with high affinity to paired helical filaments (PHF). However, high levels of 18 F-THK5351 retention in brain regions thought to contain negligible concentrations of PHF raise questions about the interpretation of the positron emission tomography (PET) signals, particularly given previously described interactions between quinolone derivatives and monoamine oxidase B (MAO-B). Here, we tested the effects of MAO-B inhibition on 18 F-THK5351 brain uptake using PET and autoradiography. Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline 18 F-AZD4694 and 18 F-THK5351 scans in order to quantify brain amyloid and PHF load, respectively. A second 18 F-THK5351 scan was conducted 1 week later, 1 h after a 10-mg oral dose of selegiline. Three out of eight patients also had a third 18 F-THK5351 scan 9-28 days after the selegiline administration. The primary outcome measure was standardized uptake value (SUV), calculated using tissue radioactivity concentration from 50 to 70 min after 18 F-THK5351 injection, normalizing for body weight and injected radioactivity. The SUV ratio (SUVR) was determined using the cerebellar cortex as the reference region. 18 F-THK5351 competition autoradiography studies in postmortem tissue were conducted using 150 and 500 nM selegiline. At baseline, 18 F-THK5351 SUVs were highest in the basal ganglia (0.64 ± 0.11) and thalamus (0.62 ± 0.14). In the post-selegiline scans, the regional SUVs were reduced on average by 36.7% to 51.8%, with the greatest reduction noted in the thalamus (51.8%) and basal ganglia (51.4%). MAO-B inhibition also reduced 18 F-THK5351 SUVs in the cerebellar cortex (41.6%). The SUVs remained reduced in the three patients imaged at 9-28 days. Tissue autoradiography confirmed the effects of MAO-B inhibition on 18 F-THK5351 uptake. These results indicate that the interpretation of 18 F

Role of Fluorine-18-Fluorodeoxyglucose in the Work-up of Febrile AIDS Patients. Experience with Dual Head Coincidence Imaging.

PubMed

Santiago, Jonas F.; Jana, Suman; Gilbert, Holly M.; Salem, Shahenda; Bellman, Paul Curtis; Hsu, Ricky K.S.; Naddaf, Sleiman; Abdel-Dayem, Hussein M.

1999-11-01

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner.

Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

PubMed

Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

1999-05-01

Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

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

Synthesis, radiolabeling, and biological evaluation of ( R)- and ( S)-2-amino-5-[ 18F]fluoro-2-methylpentanoic acid (( R)-, ( S)-[ 18F]FAMPe) as potential positron emission tomography tracers for brain tumors

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

Bouhlel, Ahlem; Zhou, Dong; Li, Aixiao

In this paper, a novel 18F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[ 18F]fluoro-2-methylpentanoic acid ([ 18F]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [ 18F]FAMPe were obtained in good radiochemical yield (24–52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that ( S)-[ 18F]FAMPe enters cells partly via sodium-independent system L transporters and also via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and smallmore » animal PET/CT studies in the mouse DBT model of glioblastoma showed that both ( R)- and ( S)-[ 18F]FAMPe have good tumor imaging properties with the ( S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Finally, comparison of the SUVs showed that ( S)-[ 18F]FAMPe had higher tumor to brain ratios compared to ( S)-[ 18F]FET, a well-established system L substrate.« less

Synthesis, radiolabeling, and biological evaluation of ( R)- and ( S)-2-amino-5-[ 18F]fluoro-2-methylpentanoic acid (( R)-, ( S)-[ 18F]FAMPe) as potential positron emission tomography tracers for brain tumors

DOE PAGES

Bouhlel, Ahlem; Zhou, Dong; Li, Aixiao; ...

2015-04-06

In this paper, a novel 18F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[ 18F]fluoro-2-methylpentanoic acid ([ 18F]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [ 18F]FAMPe were obtained in good radiochemical yield (24–52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that ( S)-[ 18F]FAMPe enters cells partly via sodium-independent system L transporters and also via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and smallmore » animal PET/CT studies in the mouse DBT model of glioblastoma showed that both ( R)- and ( S)-[ 18F]FAMPe have good tumor imaging properties with the ( S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Finally, comparison of the SUVs showed that ( S)-[ 18F]FAMPe had higher tumor to brain ratios compared to ( S)-[ 18F]FET, a well-established system L substrate.« less

Prospective Evaluation of 18F-Fluorodeoxyglucose Uptake in Postischemic Myocardium by Simultaneous Positron Emission Tomography/Magnetic Resonance Imaging as a Prognostic Marker of Functional Outcome.

PubMed

Rischpler, Christoph; Dirschinger, Ralf J; Nekolla, Stephan G; Kossmann, Hans; Nicolosi, Stefania; Hanus, Franziska; van Marwick, Sandra; Kunze, Karl P; Meinicke, Alexander; Götze, Katharina; Kastrati, Adnan; Langwieser, Nicolas; Ibrahim, Tareq; Nahrendorf, Matthias; Schwaiger, Markus; Laugwitz, Karl-Ludwig

2016-04-01

The immune system orchestrates the repair of infarcted myocardium. Imaging of the cellular inflammatory response by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/magnetic resonance imaging in the heart has been demonstrated in preclinical and clinical studies. However, the clinical relevance of post-MI (18)F-FDG uptake in the heart has not been elucidated. The objective of this study was to explore the value of (18)F-FDG positron emission tomography/magnetic resonance imaging in patients after acute myocardial infarction as a biosignal for left ventricular functional outcome. We prospectively enrolled 49 patients with ST-segment-elevation myocardial infarction and performed (18)F-FDG positron emission tomography/magnetic resonance imaging 5 days after percutaneous coronary intervention and follow-up cardiac magnetic resonance imaging after 6 to 9 months. In a subset of patients, (99m)Tc-sestamibi single-photon emission computed tomography was performed with tracer injection before revascularization. Cellular innate immune response was analyzed at multiple time points. Segmental comparison of (18)F-FDG-uptake and late gadolinium enhancement showed substantial overlap (κ=0.66), whereas quantitative analysis demonstrated that (18)F-FDG extent exceeded late gadolinium enhancement extent (33.2±16.2% left ventricular myocardium versus 20.4±10.6% left ventricular myocardium, P<0.0001) and corresponded to the area at risk (r=0.87, P<0.0001). The peripheral blood count of CD14(high)/CD16(+) monocytes correlated with the infarction size and (18)F-FDG signal extent (r=0.53, P<0.002 and r=0.42, P<0.02, respectively). (18)F-FDG uptake in the infarcted myocardium was highest in areas with transmural scar, and the standardized uptake valuemean was associated with left ventricular functional outcome independent of infarct size (Δ ejection fraction: P<0.04, Δ end-diastolic volume: P<0.02, Δ end-systolic volume: P<0.005). In this study, the intensity of (18

Pretreatment maximum standardized uptake value of (18)F-fluorodeoxyglucose positron emission tomography as a predictor of distant metastasis in adenoid cystic carcinoma of the head and neck.

PubMed

Kim, Donghyun; Kim, Wontaek; Lee, Joohye; Ki, Yongkan; Lee, Byungjoo; Cho, Kyusup; Kim, Seongjang; Nam, Jiho; Lee, Jinchoon; Kim, Dongwon

2016-05-01

The purpose of this study was to determine whether the maximum standardized uptake value (SUVmax) of the primary tumor on pretreatment (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has prognostic significance in patients with adenoid cystic carcinoma (ACC) of the head and neck. A retrospective review was carried out on 34 patients with ACC of the head and neck who underwent pretreatment (18)F-FDG PET imaging from June 2005 through July 2009. All patients underwent surgery with curative intent, and 26 of them received adjuvant radiotherapy (RT). When subjects were stratified into 2 groups according to a cutoff value for SUVmax of 4.15, the risk of distant metastasis was significantly high in patients with high SUVmax (p = .014). Multivariate analysis showed that high SUVmax and histologic grade 3 were independent poor prognostic factors for distant metastasis-free and disease-free survival. Pretreatment SUVmax of the primary tumor is an independent prognostic factor in patients with ACC of the head and neck. © 2015 Wiley Periodicals, Inc.

Evaluation of treatment response and resistance in metastatic renal cell cancer (mRCC) using integrated 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI); The REMAP study.

PubMed

Kelly-Morland, Christian; Rudman, Sarah; Nathan, Paul; Mallett, Susan; Montana, Giovanni; Cook, Gary; Goh, Vicky

2017-06-02

Tyrosine kinase inhibitors are the first line standard of care for treatment of metastatic renal cell carcinoma (RCC). Accurate response assessment in the setting of antiangiogenic therapies remains suboptimal as standard size-related response criteria do not necessarily accurately reflect clinical benefit, as they may be less pronounced or occur later in therapy than devascularisation. The challenge for imaging is providing timely assessment of disease status allowing therapies to be tailored to ensure ongoing clinical benefit. We propose that combined assessment of morphological, physiological and metabolic imaging parameters using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ( 18 F-FDG PET/MRI) will better reflect disease behaviour, improving assessment of response/non-response/relapse. The REMAP study is a single-centre prospective observational study. Eligible patients with metastatic renal cell carcinoma, planned for systemic therapy, with at least 2 lesions will undergo an integrated 18 F-FDG PET and MRI whole body imaging with diffusion weighted and contrast-enhanced multiphasic as well as standard anatomical MRI sequences at baseline, 12 weeks and 24 weeks of systemic therapy allowing 18 F-FDG standardised uptake value (SUV), apparent diffusion co-efficient (ADC) and normalised signal intensity (SI) parameters to be obtained. Standard of care contrast-enhanced computed tomography CT scans will be performed at equivalent time-points. CT response categorisation will be performed using RECIST 1.1 and alternative (modified)Choi and MASS criteria. The reference standard for disease status will be by consensus panel taking into account clinical, biochemical and conventional imaging parameters. Intra- and inter-tumoural heterogeneity in vascular, diffusion and metabolic response/non-response will be assessed by image texture analysis. Imaging will also inform the development of computational methods for automated disease status

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

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

Specific binding of [(18)F]fluoroethyl-harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain.

PubMed

Maschauer, Simone; Haller, Adelina; Riss, Patrick J; Kuwert, Torsten; Prante, Olaf; Cumming, Paul

2015-12-01

We investigated [(18)F]fluoroethyl-harmol ([(18)F]FEH) as a reversible and selective ligand for positron emission tomography (PET) studies of monoamine oxidase A (MAO-A). Binding of [(18)F]FEH in rat brain cryostat sections indicated high affinity (KD = 3 nM), and density (Bmax; 600 pmol/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10 min after injection. Compartmental analysis of PET recordings in pargyline-treated rats showed high permeability to brain (K1; 0.32 mL/g/min) and slow washout (k2; 0.024/min), resulting in a uniformly high equilibrium distribution volume (VD; 20 mL/g). Using this VD to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [(18)F]FEH at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex KD was globally close to 300 nM and Bmax was close to 1600 pmol/g; the 100-fold discrepancy in affinity suggests a very low free fraction for [(18)F]FEH in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4 μM in the striatal compartment containing MAO-A, thus unlikely to exert competition against [(18)F]FEH binding in vivo. In summary, [(18)F]FEH has good properties for the detection of MAO-A in the rat brain by PET, and may present logistic advantages for clinical research at centers lacking a medical cyclotron. We made a compartmental analysis of [(18)F]fluoroethylharmol ([(18)F]FEH) binding to monoamine oxidase A (MAO-A) in living rat brain and estimated the saturation binding parameters from the binding potential (BPND). The Bmax was of comparable magnitude to that in vitro, but with apparent affinity (300 nM), it was 100-fold lower in vivo. PET imaging with [(18) F]FEH is well suited for quantitation of MAO-A in living

Tumor Delineation and Quantitative Assessment of Glucose Metabolic Rate within Histologic Subtypes of Non-Small Cell Lung Cancer by Using Dynamic 18F Fluorodeoxyglucose PET.

PubMed

Meijer, Tineke W H; de Geus-Oei, Lioe-Fee; Visser, Eric P; Oyen, Wim J G; Looijen-Salamon, Monika G; Visvikis, Dimitris; Verhagen, Ad F T M; Bussink, Johan; Vriens, Dennis

2017-05-01

Purpose To assess whether dynamic fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) has added value over static 18 F-FDG PET for tumor delineation in non-small cell lung cancer (NSCLC) radiation therapy planning by using pathology volumes as the reference standard and to compare pharmacokinetic rate constants of 18 F-FDG metabolism, including regional variation, between NSCLC histologic subtypes. Materials and Methods The study was approved by the institutional review board. Patients gave written informed consent. In this prospective observational study, 1-hour dynamic 18 F-FDG PET/computed tomographic examinations were performed in 35 patients (36 resectable NSCLCs) between 2009 and 2014. Static and parametric images of glucose metabolic rate were obtained to determine lesion volumes by using three delineation strategies. Pathology volume was calculated from three orthogonal dimensions (n = 32). Whole tumor and regional rate constants and blood volume fraction (V B ) were computed by using compartment modeling. Results Pathology volumes were larger than PET volumes (median difference, 8.7-25.2 cm 3 ; Wilcoxon signed rank test, P < .001). Static fuzzy locally adaptive Bayesian (FLAB) volumes corresponded best with pathology volumes (intraclass correlation coefficient, 0.72; P < .001). Bland-Altman analyses showed the highest precision and accuracy for static FLAB volumes. Glucose metabolic rate and 18 F-FDG phosphorylation rate were higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AC), whereas V B was lower (Mann-Whitney U test or t test, P = .003, P = .036, and P = .019, respectively). Glucose metabolic rate, 18 F-FDG phosphorylation rate, and V B were less heterogeneous in AC than in SCC (Friedman analysis of variance). Conclusion Parametric images are not superior to static images for NSCLC delineation. FLAB-based segmentation on static 18 F-FDG PET images is in best agreement with pathology volume and could be useful

The Accuracy of Integrated [18F] Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Detection of Pelvic and Para-aortic Nodal Metastasis in Patients with High Risk Endometrial Cancer

PubMed Central

Gholkar, Nikhil Shirish; Saha, Subhas Chandra; Prasad, GRV; Bhattacharya, Anish; Srinivasan, Radhika; Suri, Vanita

2014-01-01

Lymph nodal (LN) metastasis is the most important prognostic factor in high-risk endometrial cancer. However, the benefit of routine lymphadenectomy in endometrial cancer is controversial. This study was conducted to assess the accuracy of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography ([18F] FDG-PET/CT) in detection of pelvic and para-aortic nodal metastases in high-risk endometrial cancer. 20 patients with high-risk endometrial carcinoma underwent [18F] FDG-PET/CT followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy. The findings on histopathology were compared with [18F] FDG-PET/CT findings to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F] FDG-PET/CT. The pelvic nodal findings were analyzed on a patient and nodal chain based criteria. The para-aortic nodal findings were reported separately. Histopathology documented nodal involvement in two patients (10%). For detection of pelvic nodes, on a patient based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 61.11%, PPV of 22.22%, NPV of 100% and accuracy of 65% and on a nodal chain based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 80%, PPV of 20%, NPV of 100%, and accuracy of 80.95%. For detection of para-aortic nodes, [18F] FDG-PET/CT had sensitivity of 100%, specificity of 66.67%, PPV of 20%, NPV of 100%, and accuracy of 69.23%. Although [18F] FDG-PET/CT has high sensitivity for detection of LN metastasis in endometrial carcinoma, it had moderate accuracy and high false positivity. However, the high NPV is important in selecting patients in whom lymphadenectomy may be omitted. PMID:25538488

Incidence of Brain Metastases on Follow-up 18F-FDG PET/CT Scans of Non-Small Cell Lung Cancer Patients: Should We Include the Brain?

PubMed

Nia, Emily S; Garland, Linda L; Eshghi, Naghmehossadat; Nia, Benjamin B; Avery, Ryan J; Kuo, Phillip H

2017-09-01

The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18 F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18 F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18 F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18 F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18 F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18 F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18 F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18 F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18 F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution. © 2017 by the Society of

Prevalence and prognosis of prodromal Alzheimer's disease as assessed by magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography in a community: reanalysis from the Osaki-Tajiri Project.

PubMed

Meguro, Kenichi; Akanuma, Kyoko; Meguro, Mitsue; Yamaguchi, Satoshi; Ishii, Hiroshi; Tashiro, Manabu

2016-03-01

Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and (18) F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated. Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging). Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period. The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Evaluation of chemotherapy response in patients with advanced head and neck cancer using [F-18]fluorodeoxyglucose positron emission tomography.

PubMed

Lowe, V J; Dunphy, F R; Varvares, M; Kim, H; Wittry, M; Dunphy, C H; Dunleavy, T; McDonough, E; Minster, J; Fletcher, J W; Boyd, J H

1997-12-01

[F-18]Fluorodeoxyglucose (FDG)-positron emission tomography (PET) can measure the metabolic activity of tissues; FDG-PET may be able to predict response to chemotherapy by identifying changes in tumor metabolism. Measurement of response to treatment may help improve survival in the management of advanced head and neck cancer. We evaluated this particular use of FDG-PET in patients participating in a neoadjuvant organ-preservation protocol using taxol and carboplatin and compared pathologic response after chemotherapy with changes in tumor metabolism measured by FDG-PET. Serial FDG-PET studies (n = 56) were performed in patients (n = 28) with stage III/IV head and neck cancer participating in a neoadjuvant organ-preservation protocol. The FDG-PET studies were performed before and after chemotherapy. All patients had tissue biopsies before and after chemotherapy. Patients were classified as pathologic complete response (PCR) or residual disease (RD) based on tissue biopsies. Visual analysis of PET scans was performed to identify patients with complete response by PET, and these findings were compared with pathology results. Metabolic changes were also evaluated using standardized uptake ratios (SUR) of FDG. The sensitivity and specificity of PET for residual cancer after therapy was 90% (19/21) and 83% (5/6), respectively. Two patients had initially negative biopsies and positive PET studies for persistent disease. Pathology review and rebiospy led to confirmation of the PET results in these cases, giving a sensitivity of 90% for initial tissue biopsy. In this preliminary analysis, FDG-PET was accurate in classifying response to chemotherapy in most patients. Fluorodeoxyglucose-PET may identify residual viable tumor when it is otherwise undetectable.

Utility of 18F-fluorodeoxyglucose-positron emission tomography in the differential diagnosis of benign and malignant gynaecological tumours.

PubMed

Takagi, Hiroaki; Sakamoto, Jinichi; Osaka, Yasuhiro; Shibata, Takeo; Fujita, Satoko; Sasagawa, Toshiyuki

2018-02-05

Positron emission tomography/computed tomography (PET/CT) involving 18F-fluorodeoxyglucose (FDG) is widely used for systemic cancer and recurrence diagnosis. However, the differential diagnosis of benign and malignant gynaecological tumours according to FDG accumulation is unclear. This study aimed to investigate the intensity of FDG uptake/metabolic activity for the differential diagnosis of benign and malignant gynaecological tumours. This study included seven patients with physiological phenomena, 34 with benign tumours, 13 with borderline malignant tumours and 119 with malignant tumours who underwent 18F-FDG PET/CT. We assessed the maximum standardized uptake value (SUVmax) and determined its utility in the diagnosis of benign and malignant tumours using a receiver operating characteristic (ROC) curve analysis. Among the 63 patients with ovarian tumours, the mean SUVmax of 22 patients with benign ovarian tumours was 2.48 and the mean SUVmax of 41 patients with malignant ovarian tumours was 10.98 (P < 0.001). In the ROC curve analysis, the area under the curve (AUC) was 0.977, with a 95% confidence interval of 0.947-1.000. With a cut-off value of 3.97 for the optimal SUVmax, the sensitivity and specificity were 95.1% and 86.4%, respectively. In addition, the AUC was 0.911 (95% CI: 0.768-1.000) for the assessment of uterine myomas and sarcomas. With a cut-off value of 10.62 for the optimal SUVmax, the sensitivity and specificity were 91.7% and 86.7% respectively. The SUVmax value helps differentiate benign and malignant ovarian tumours, as well as uterine myomas and uterine sarcomas. © 2018 The Royal Australian and New Zealand College of Radiologists.

HDAC6 Brain Mapping with [ 18 F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination

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

Strebl, Martin G.; Campbell, Arthur J.; Zhao, Wen -Ning

Histone deacetylase 6 (HDAC6) function and dysregulation have been implicated in the etiology of certain cancers and more recently in central nervous system (CNS) disorders including Rett syndrome, Alzheimer’s and Parkinson’s diseases, and major depressive disorder. HDAC6-selective inhibitors have therapeutic potential, but in the CNS drug space the development of highly brain penetrant HDAC inhibitors has been a persistent challenge. Moreover, no tool exists to directly characterize HDAC6 and its related biology in the living human brain. Here, we report a highly brain penetrant HDAC6 inhibitor, Bavarostat, that exhibits excellent HDAC6 selectivity (>80-fold over all other Zn-containing HDAC paralogues), modulatesmore » tubulin acetylation selectively over histone acetylation, and has excellent brain penetrance. We further demonstrate that Bavarostat can be radiolabeled with 18F by deoxyfluorination through in situ formation of a ruthenium π-complex of the corresponding phenol precursor: the only method currently suitable for synthesis of [ 18F]Bavarostat. In conclusion, by using [ 18F]Bavarostat in a series of rodent and nonhuman primate imaging experiments, we demonstrate its utility for mapping HDAC6 in the living brain, which sets the stage for first-in-human neurochemical imaging of this important target.« less

HDAC6 Brain Mapping with [ 18 F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination

DOE PAGES

Strebl, Martin G.; Campbell, Arthur J.; Zhao, Wen -Ning; ...

2017-09-06

Histone deacetylase 6 (HDAC6) function and dysregulation have been implicated in the etiology of certain cancers and more recently in central nervous system (CNS) disorders including Rett syndrome, Alzheimer’s and Parkinson’s diseases, and major depressive disorder. HDAC6-selective inhibitors have therapeutic potential, but in the CNS drug space the development of highly brain penetrant HDAC inhibitors has been a persistent challenge. Moreover, no tool exists to directly characterize HDAC6 and its related biology in the living human brain. Here, we report a highly brain penetrant HDAC6 inhibitor, Bavarostat, that exhibits excellent HDAC6 selectivity (>80-fold over all other Zn-containing HDAC paralogues), modulatesmore » tubulin acetylation selectively over histone acetylation, and has excellent brain penetrance. We further demonstrate that Bavarostat can be radiolabeled with 18F by deoxyfluorination through in situ formation of a ruthenium π-complex of the corresponding phenol precursor: the only method currently suitable for synthesis of [ 18F]Bavarostat. In conclusion, by using [ 18F]Bavarostat in a series of rodent and nonhuman primate imaging experiments, we demonstrate its utility for mapping HDAC6 in the living brain, which sets the stage for first-in-human neurochemical imaging of this important target.« less

Effects of glucose, insulin, and insulin resistance on cerebral 18F-FDG distribution in cognitively normal older subjects

PubMed Central

Onishi, Airin; Fujiwara, Yoshinori; Ishiwata, Kiichi; Ishii, Kenji

2017-01-01

Background Increasing plasma glucose levels and insulin resistance can alter the distribution pattern of fluorine-18-labeled fluorodeoxyglucose (18F-FDG) in the brain and relatively reduce 18F-FDG uptake in Alzheimer's disease (AD)-related hypometabolic regions, leading to the appearance of an AD-like pattern. However, its relationship with plasma insulin levels is unclear. We aimed to compare the effects of plasma glucose levels, plasma insulin levels and insulin resistance on the appearance of the AD-like pattern in 18F-FDG images. Methods Fifty-nine cognitively normal older subjects (age = 75.7 ± 6.4 years) underwent 18F-FDG positron emission tomography along with measurement of plasma glucose and insulin levels. As an index of insulin resistance, the Homeostasis model assessment of Insulin Resistance (HOMA-IR) was calculated. Results Plasma glucose levels, plasma insulin levels, and HOMA-IR were 102.2 ± 8.1 mg/dL, 4.1 ± 1.9 μU/mL, and 1.0 ± 0.5, respectively. Whole-brain voxelwise analysis showed a negative correlation of 18F-FDG uptake with plasma glucose levels in the precuneus and lateral parietotemporal regions (cluster-corrected p < 0.05), and no correlation with plasma insulin levels or HOMA-IR. In the significant cluster, 18F-FDG uptake decreased by approximately 4–5% when plasma glucose levels increased by 20 mg/dL. In the precuneus region, volume-of-interest analysis confirmed a negative correlation of 18F-FDG uptake with plasma glucose levels (r = -0.376, p = 0.002), and no correlation with plasma insulin levels (r = 0.156, p = 0.12) or HOMA-IR (r = 0.096, p = 0.24). Conclusion This study suggests that, of the three parameters, plasma glucose levels have the greatest effect on the appearance of the AD-like pattern in 18F-FDG images. PMID:28715453

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

PubMed Central

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

2015-01-01

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

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

Imaging atherosclerosis with hybrid [18F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: what Leonardo da Vinci could not see.

PubMed

Cocker, Myra S; Mc Ardle, Brian; Spence, J David; Lum, Cheemun; Hammond, Robert R; Ongaro, Deidre C; McDonald, Matthew A; Dekemp, Robert A; Tardif, Jean-Claude; Beanlands, Rob S B

2012-12-01

Prodigious efforts and landmark discoveries have led toward significant advances in our understanding of atherosclerosis. Despite significant efforts, atherosclerosis continues globally to be a leading cause of mortality and reduced quality of life. With surges in the prevalence of obesity and diabetes, atherosclerosis is expected to have an even more pronounced impact upon the global burden of disease. It is imperative to develop strategies for the early detection of disease. Positron emission tomography (PET) imaging utilizing [(18)F]fluorodeoxyglucose (FDG) may provide a non-invasive means of characterizing inflammatory activity within atherosclerotic plaque, thus serving as a surrogate biomarker for detecting vulnerable plaque. The aim of this review is to explore the rationale for performing FDG imaging, provide an overview into the mechanism of action, and summarize findings from the early application of FDG PET imaging in the clinical setting to evaluate vascular disease. Alternative imaging biomarkers and approaches are briefly discussed.

Florbetapir (18F) for brain amyloid positron emission tomography: highlights on the European marketing approval.

PubMed

Cortes-Blanco, Anabel; Prieto-Yerro, Concha; Martinez-Lazaro, Raul; Zamora, Javier; Jiménez-Huete, Adolfo; Haberkamp, Marion; Pohly, Johannes; Enzmann, Harald; Zinserling, Jörg; Strassmann, Valerie; Broich, Karl

2014-10-01

Florbetapir (18F) for brain amyloid positron emission tomography (PET) imaging has been recently approved in Europe to estimate β-amyloid neuritic plaque density in the brain when the subject is still alive. Such density is one of the key issues for the definitive diagnosis of Alzheimer's disease (AD) at autopsy. This capability of florbetapir (18F) is regarded as a significant improvement in the diagnostic procedures for adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive impairment. The current paper highlights the specific characteristics of the European marketing authorization of florbetapir (18F). Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

PubMed

Stegmayr, Carina; Stoffels, Gabriele; Kops, Elena Rota; Lohmann, Philipp; Galldiks, Norbert; Shah, Nadim J; Neumaier, Bernd; Langen, Karl-Josef

2018-05-29

O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [ 18 F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR). [ 18 F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [ 18 F]FET uptake in the normal brain (SUV brain ) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy. SUV brain of [ 18 F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUV brain 1.33 ± 0.1 versus 1.06 ± 0.16 in male and 1.45 ± 0.25 versus 1.31 ± 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUV brain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBR max and TBR mean , which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBR max and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUV brain . Dexamethasone treatment appears to increase the [ 18 F]FET uptake in the normal brain. An effect on TBR max , TBR mean , and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [ 18 F]FET PET.

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

PubMed

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

2018-06-07

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

[18F]fluorodeoxyglucose triple-head coincidence imaging as an adjunct to 131I scanning for follow-up of papillary thyroid carcinoma.

PubMed

Gonzalo, Irene T Gaw; Itti, Emmanuel; Mlikotic, Anton; Pham, Le H; Cesar, Romeo B; Meignan, Michel; Mishkin, Fred S

2003-01-01

To evaluate the feasibility of using [(18)F]fluorodeoxyglucose ((18)FDG) triple-head coincidence imaging as a potential cost-effective alternative to positron emission tomography in the setting of suspected recurrence of papillary thyroid carcinoma. We retrospectively studied 10 patients with suspected recurrence of papillary carcinoma of the thyroid, who underwent (18)FDG coincidence imaging,(131)I scanning, and a reference anatomic scan (computed tomography, magnetic resonance imaging, or both) within 1 year in most cases. The (131)I scan detected the recurrence in five patients (62.5%) and failed to reveal recurrent cancer in three patients (37.5%); in contrast,(18)FDG imaging detected the recurrence in eight patients (100%) and was true negative in two patients in whom the scans were performed more than 1 year after effective therapy for the recurrence. The sensitivity of detection was unrelated to lesion size. The (18)FDG imaging results led to additional radiotherapy in all (131)I-negative patients, two of whom had high thyroglobulin levels and one of whom had a low thyroglobulin concentration but the presence of antithy-roglobulin antibodies. We conclude that (18)FDG triple-head coincidence imaging is useful for routine management of patients with thyroid cancer who have no abnormalities detected on (131)I scans but have high serum thyroglobulin levels. This technique, however, may not be as sensitive as a dedicated positron emission tomographic device, particularly for the assessment of small tumors.

Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data

PubMed Central

Cha, Ji Hyeon; Lee, Sheen-Woo; Park, Kyeongsoon; Moon, Dae Hyuk; Kim, Kwangmeyung; Biswal, Sandip

2012-01-01

Objective To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA). Materials and Methods We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 µL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice. Results The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 ± 0.76 and 0.79 ± 0.71, respectively, for CIA mice; and 0.57 ± 0.17 and 0.54 ± 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 ± 1.54 × 105 and 2.75 ± 1.51 × 105, respectively, for CIA mice, and 1.22 ± 0.27 × 105 and 0.88 ± 0.24 × 105, respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice. Conclusion NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis. PMID:22778567

Role of (18)F-FDG PET-CT in Monitoring the Cyclophosphamide Induced Pulmonary Toxicity in Patients with Breast Cancer - 2 Case Reports.

PubMed

Taywade, Sameer Kamalakar; Kumar, Rakesh; Bhethanabhotla, Sainath; Bal, Chandrasekhar

2016-09-01

Drug induced pulmonary toxicity is not uncommon with the use of various chemotherapeutic agents. Cyclophosphamide is a widely used chemotherapeutic drug in the treatment of breast cancer. Although rare, lung toxicity has been reported with cyclophosphamide use. Detection of bleomycin induced pulmonary toxicity and pattern of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in lungs on fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) has been elicited in literature in relation to lymphoma. However, limited data is available regarding the role of (18)F-FDG PET-CT in monitoring drug induced pulmonary toxicity in breast cancer. We here present two cases of cyclophosphamide induced drug toxicity. Interim (18)F-FDG PET-CT demonstrated diffusely increased tracer uptake in bilateral lung fields in both these patients. Subsequently there was resolution of lung uptake on (18)F-FDG PET-CT scan post completion of chemotherapy. These patients did not develop significant respiratory symptoms during chemotherapy treatment and in follow up.

Characterizing the normative profile of 18F-FDG PET brain imaging: sex difference, aging effect, and cognitive reserve.

PubMed

Yoshizawa, Hiroshi; Gazes, Yunglin; Stern, Yaakov; Miyata, Yoko; Uchiyama, Shinichiro

2014-01-30

The aim of this study was to investigate findings of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) in normal subjects to clarify the effects of sex differences, aging, and cognitive reserve on cerebral glucose metabolism. Participants comprised 123 normal adults who underwent 18F-FDG PET and a neuropsychological battery. We used statistical parametric mapping (SPM8) to investigate sex differences, and aging effects. The effects of cognitive reserve on 18F-FDG uptake were investigated using years of education as a proxy. Finally, we studied the effect of cognitive reserve on the recruitment of glucose metabolism in a memory task by dichotomizing the data according to educational level. Our results showed that the overall cerebral glucose metabolism in females was higher than that in males, whereas male participants had higher glucose metabolism in the bilateral inferior temporal gyri and cerebellum than females. Age-related hypometabolism was found in anterior regions, including the anterior cingulate gyrus. These areas are part of the attentional system, which may decline with aging even in healthy elderly individuals. Highly educated subjects revealed focal hypermetabolism in the right hemisphere and lower recruitment of glucose metabolism in memory tasks. This phenomenon is likely a candidate for a neural substrate of cognitive reserve. © 2013 Published by Elsevier Ireland Ltd.

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

PubMed

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

2012-04-01

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

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.

PubMed

Barrio, Jorge R; Small, Gary W; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A; Giza, Christopher C; Fitzsimmons, Robert P; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-04-21

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

PubMed Central

Barrio, Jorge R.; Small, Gary W.; Wong, Koon-Pong; Huang, Sung-Cheng; Liu, Jie; Merrill, David A.; Giza, Christopher C.; Fitzsimmons, Robert P.; Omalu, Bennet; Bailes, Julian; Kepe, Vladimir

2015-01-01

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. PMID:25848027

[11C] methionine and [18F] fluorodeoxyglucose PET in the follow-up of glioblastoma multiforme.

PubMed

Pötzi, Christian; Becherer, Alexander; Marosi, Christine; Karanikas, Georgios; Szabo, Monika; Dudczak, Robert; Kletter, Kurt; Asenbaum, Susanne

2007-09-01

The aim of this study was to evaluate the value of [11C] methionine (MET) and [18F] fluorodeoxyglucose (FDG) PET in the follow-up of glioblastoma multiforme (GBM). After surgical and/or conservative treatment, 28 patients (pts) with GBM underwent FDG and MET PET on average 12.7 months after the diagnosis had been established. Scans were evaluated visually and by calculating the maximal tumor SUV as well as the ratio of tumor vs. contralateral region (RTu). The degree of tracer uptake was compared with survival time, disease duration and MRI findings. The mean overall duration of survival was 12.7 months. The patients were divided into two groups: those that survived less than 12 months and those that survived longer than 12 months. Focally increased uptake was revealed by MET PET in 24 patients and by FDG PET in 2 patients. On MRI scans, viable tumor tissue was suspected in 18 patients. No correlations were registered between FDG/MET uptake and survival time or disease duration respectively; Kaplan-Meier calculations were negative in this regard. Similarly, negative results were obtained in subgroups of patients who had undergone microsurgical resection and whose disease was at least of 6 months' duration, and additionally in a subgroup who had undergone their last treatment longer than 6 months ago. With respect to survival groups, a positive MET PET was associated with a sensitivity of 86% and a specificity of 8%. SUV and RTu values did not differ between patients with positive or negative MRI results. In this study FDG PET seems to be of limited value in the work-up of recurrent GBM because of its lower sensitivity than MET PET and the fact that it allows no prediction of the outcome. MET PET visualizes viable tumor tissue without adding any prognostic information and appears to be in no way superior to conventional imaging.

Imaging of VMAT2 binding sites in the brain by (18)F-AV-133: the effect of a pseudo-carrier.

PubMed

Zhu, Lin; Qiao, Hongwen; Lieberman, Brian P; Wu, Jingxiao; Liu, Yajing; Pan, Zhongyun; Ploessl, Karl; Choi, Seok Rye; Chan, Piu; Kung, Hank F

2012-10-01

Recently, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of (18)F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using (18)F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative (18)F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. The radiochemical purity of the (18)F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250 μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of (18)F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). The pseudo-carrier, AV-149, did not affect the (18)F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable (18)F-AV-133 to be widely available for routine clinical application in

Three-dimensional positron emission tomography image texture analysis of esophageal squamous cell carcinoma: relationship between tumor 18F-fluorodeoxyglucose uptake heterogeneity, maximum standardized uptake value, and tumor stage.

PubMed

Dong, Xinzhe; Xing, Ligang; Wu, Peipei; Fu, Zheng; Wan, Honglin; Li, Dengwang; Yin, Yong; Sun, Xiaorong; Yu, Jinming

2013-01-01

To explore the relationship of a new PET image parameter, (18)F-fluorodeoxyglucose ((18)F-FDG) uptake heterogeneity assessed by texture analysis, with maximum standardized uptake value (SUV(max)) and tumor TNM staging. Forty consecutive patients with esophageal squamous cell carcinoma were enrolled. All patients underwent whole-body preoperative (18)F-FDG PET/CT. Heterogeneity of intratumoral (18)F-FDG uptake was assessed on the basis of the textural features (entropy and energy) of the three-dimensional images using MATLAB software. The correlations between the textural parameters and SUV(max), histological grade, tumor location, and TNM stage were analyzed. Tumors with higher SUV(max) were seen to be more heterogenous on (18)F-FDG uptake. Significant correlations were observed between T stage and SUV(max) (r(s)=0.390, P=0.013), entropy (rs=0.693, P<0.001), and energy (r(s)=-0.469, P=0.002). Correlations were also found between SUV(max), entropy, energy, and N stage (r(s)=0.326, P=0.04; r(s)=0.501, P=0.001; r(s)=-0.413, P=0.008). The American Joint Committee on Cancer stage correlated significantly with all metabolic parameters. The receiver-operating characteristic curve demonstrated an entropy of 4.699 as the optimal cutoff point for detecting tumors above stage II(b) with an areas under the ROC curve of 0.789 (P<0.001). This study provides initial evidence for the relationship between the new parameter of tumor uptake heterogeneity and the commonly used simplistic parameter of SUV and tumor stage. Our findings suggest a complementary role of these parameters in the staging and prognosis of esophageal squamous cell carcinoma.

Comparison of Core-Needle Biopsy and Fine-Needle Aspiration for Evaluating Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: A Propensity Score Analysis.

PubMed

Suh, Chong Hyun; Choi, Young Jun; Lee, Jong Jin; Shim, Woo Hyun; Baek, Jung Hwan; Chung, Han Cheol; Shong, Young Kee; Song, Dong Eun; Sung, Tae Yon; Lee, Jeong Hyun

2017-10-01

This study used a propensity score analysis to assess the roles of core-needle biopsy (CNB) and fine-needle aspiration (FNA) in the evaluation of thyroid incidentalomas detected on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). The study population was obtained from a historical cohort who underwent 18 F-FDG PET/CT between October 2008 and September 2015. Patients were included who underwent ultrasound-guided CNB or FNA for incidental focal uptake of 18 F-FDG in the thyroid gland on PET/CT. The primary study outcomes included the inconclusive result rates in the CNB and FNA groups. The secondary outcome measures included the non-diagnostic result rate and the diagnostic performance for neoplasms. Multivariate analysis, propensity score matching, and inverse probability weighting were conducted. A total of 1360 nodules from 1338 patients were included in this study: 859 nodules from 850 patients underwent FNA, and 501 nodules from 488 patients underwent CNB. Compared to FNA, CNB demonstrated a significantly lower inconclusive result rate in the pooled cohort (23.8% vs. 35.4%; p < 0.001), propensity score-matched cohorts (22.9% vs. 36.6%; p < 0.001), and with inverse probability weighting (22.4% vs. 35.2%; p < 0.001). Non-diagnostic result rates were also significantly lower in CNB than in FNA. The diagnostic performance of the two groups in the pooled and matched cohorts was similar, with no significant differences found. The significantly lower inconclusive result rates in CNB than in FNA were consistent within the propensity score-matched cohorts. Therefore, CNB appears to be a promising diagnostic tool for patients with thyroid incidentalomas detected on 18 F-FDG PET/CT.

Detection of thoracic aortic prosthetic graft infection with 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

PubMed

Tokuda, Yoshiyuki; Oshima, Hideki; Araki, Yoshimori; Narita, Yuji; Mutsuga, Masato; Kato, Katsuhiko; Usui, Akihiko

2013-06-01

To investigate the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in detecting thoracic aortic prosthetic graft infection. Nine patients with clinically suspected thoracic aortic graft infection underwent FDG-PET/CT scanning. In these patients, the diagnoses could not be confirmed using conventional modalities. The patients' clinical courses were retrospectively reviewed. On the basis of surgical, microbiological and clinical follow-up findings, the aortic grafts were considered infected in 4 patients and not infected in 5. All 4 patients with graft infection (root: 2 cases, arch: 1 case and descending: 1 case) eventually underwent in situ re-replacement. Two of the 4 patients also had abdominal grafts; however, only the thoracic grafts were replaced because uptake was low around the abdominal grafts. The maximal standardized uptake value (SUVmax) in the perigraft area was higher in the infected group than in the non-infected group (11.4 ± 4.5 vs 6.9 ± 6.4), although the difference was not statistically significant. According to the receiver operating characteristic analysis, SUVmax >8 appeared to be the cut-off value in distinguishing the two groups (sensitivity: 1.0 and specificity: 0.8). FDG-PET/CT is useful for confirming the presence of graft infection by detecting high uptake around grafts and excluding other causes of inflammation. An SUVmax value greater than 8 around a graft suggests the presence of graft infection. In addition, FDG-PET/CT can be used to clarify the precise extent of infection. This is especially useful if multiple separated prosthetic grafts have been implanted.

(18)F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK).

PubMed

Hultsch, Christina; Schottelius, Margret; Auernheimer, Jörg; Alke, Andrea; Wester, Hans-Jürgen

2009-09-01

Oxime formation between an aminooxy-functionalized peptide and an (18)F-labelled aldehyde has recently been introduced as a powerful method for the rapid one-step chemoselective synthesis of radiofluorinated peptides. Here, the potential of using routinely produced and thus readily available [(18)F]fluorodeoxyglucose ([(18)F]FDG) as the aldehydic prosthetic group was investigated using an aminooxyacetyl-conjugated cyclic RGD peptide (cyclo(RGDfK(Aoa-(Boc)) as a model peptide. The use of [(18)F]FDG from routine production ([(18)F]FDGTUM) containing an excess of D: -glucose did not allow the radiosynthesis of [(18)F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [(18)F]FDG for the routine clinical synthesis of (18)F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [(18)F]FDG obtained via HPLC separation of [(18)F]FDGTUM from excess glucose, however, afforded [(18)F]FDG-RGD in yields of 56-93% (decay corrected) and activities up to 37 MBq. Suitable reaction conditions were 20 min at 120 degrees C and pH 2.5, and a peptide concentration of 5 mM. In a preliminary in vivo biodistribution study in M21 melanoma-bearing nude mice, [(18)F]FDG-RGD showed increased tumour accumulation compared to the "gold standard" [(18)F]galacto-RGD (2.18 vs 1.49 %iD/g, respectively, at 120 min after injection), but also slightly increased uptake in non-target organs, leading to comparable tumour/organ ratios for both compounds. These data demonstrate that chemoselective (18)F-labelling of aminooxy-functionalized peptides using n.c.a. [(18)F]FDG represents a radiofluorination/glycosylation strategy that allows preparation of (18)F-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [(18)F]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [(18)F]FDG-synthesis, [(18)F]fluoroglucosylation of peptides may represent a promising alternative to

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

PubMed Central

2014-01-01

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

Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An (18)F-FDG-PET study.

PubMed

Ma, Suhua; You, Shengzhong; Hao, Li; Zhang, Dongchuan; Quan, Li

2015-07-01

This study was designed to evaluate changes in brain glucose metabolism in rats following ligature strangulation. Thirteen male Wistar rats were used in the present study, divided into control (n=7) and asphyxia groups (n=6, ligature strangulation). Positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) was used to evaluate brain glucose metabolism. Rats were scanned for PET-CT, and image data co-registered with a T2WI MRI template using SPM8 software. Image J was employed to draw regions of interest (ROIs) from the MRI template and acquire ROI activity information from the PET images. In the asphyxia group vs. controls, (18)F-FDG uptake (FU) was decreased in the substantia nigra (25.26%, p<0.001), rhombencephalon (pons/medulla oblongata, 13.92%, p<0.01), hypothalamus (22.06%, p<0.01), ventral tegmentum (10.12%, p<0.05) and amygdala (12.74%, p<0.05); however, FU was increased in motor (18.21%, p<0.05) and visual cortices (19.2%, p<0.05). The glucose metabolism distribution map in the asphyxiated rat brains were substantially changed versus controls. PET with (18)F-FDG can demonstrate excitement and inhibition of different brain areas even in cases of ligature strangulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.

PubMed

Moriguchi, Sho; Kimura, Yasuyuki; Ichise, Masanori; Arakawa, Ryosuke; Takano, Harumasa; Seki, Chie; Ikoma, Yoko; Takahata, Keisuke; Nagashima, Tomohisa; Yamada, Makiko; Mimura, Masaru; Suhara, Tetsuya

2017-07-01

Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, ( S , S )- 11 C-MRB and ( S , S )- 18 F-FMeNER-D 2 , have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with ( S , S )- 11 C-MRB and defluorination with ( S , S )- 18 F-FMeNER-D 2 , which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18 F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using ( S , S )- 18 F-FMeNER-D 2 PET. Methods: We analyzed our previous ( S , S )- 18 F-FMeNER-D 2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of ( S , S )- 18 F-FMeNER-D 2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established

Characterization in humans of 18F-MNI-444, a PET radiotracer for brain adenosine 2A receptors.

PubMed

Barret, Olivier; Hannestad, Jonas; Vala, Christine; Alagille, David; Tavares, Adriana; Laruelle, Marc; Jennings, Danna; Marek, Ken; Russell, David; Seibyl, John; Tamagnan, Gilles

2015-04-01

PET with selective adenosine 2A receptor (A2A) radiotracers can be used to study a variety of neurodegenerative and neuropsychiatric disorders in vivo and to support drug-discovery studies targeting A2A. The aim of this study was to describe the first in vivo evaluation of (18)F-MNI-444, a novel PET radiotracer for imaging A2A, in healthy human subjects. Ten healthy human volunteers were enrolled in this study; 6 completed the brain PET studies and 4 participated in the whole-body PET studies. Arterial blood was collected for invasive kinetic modeling of the brain PET data. Noninvasive methods of data quantification were also explored. Test-retest reproducibility was evaluated in 5 subjects. Radiotracer distribution and dosimetry was determined using serial whole-body PET images acquired over 6 h post-radiotracer injection. Urine samples were collected to calculate urinary excretion. After intravenous bolus injection, (18)F-MNI-444 rapidly entered the brain and displayed a distribution consistent with known A2A densities in the brain. Binding potentials ranging from 2.6 to 4.9 were measured in A2A-rich regions, with an average test-retest variability of less than 10%. The estimated whole-body radiation effective dose was approximately 0.023 mSv/MBq. (18)F-MNI-444 is a useful PET radiotracer for imaging A2A in the human brain. The superior in vivo brain kinetic properties of (18)F-MNI-444, compared with previously developed A2A radiotracers, provide the opportunity to foster global use of in vivo A2A PET imaging in neuroscience research. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

PubMed

Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

2016-10-18

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

18F-FDG as an inflammation biomarker for imaging dengue virus infection and treatment response

PubMed Central

Watanabe, Satoru; Herr, Keira J.; Kalimuddin, Shirin; Tham, Jing Yang; Ong, Joanne; Reolo, Marie; Serrano, Raymond M.F.; Cheung, Yin Bun; Low, Jenny G.H.; Vasudevan, Subhash G.

2017-01-01

Development of antiviral therapy against acute viral diseases, such as dengue virus (DENV), suffers from the narrow window of viral load detection in serum during onset and clearance of infection and fever. We explored a biomarker approach using 18F-fluorodeoxyglucose (18F-FDG) PET in established mouse models for primary and antibody-dependent enhancement infection with DENV. 18F-FDG uptake was most prominent in the intestines and correlated with increased virus load and proinflammatory cytokines. Furthermore, a significant temporal trend in 18F-FDG uptake was seen in intestines and selected tissues over the time course of infection. Notably, 18F-FDG uptake and visualization by PET robustly differentiated treatment-naive groups from drug-treated groups as well as nonlethal from lethal infections with a clinical strain of DENV2. Thus, 18F-FDG may serve as a novel DENV infection–associated inflammation biomarker for assessing treatment response during therapeutic intervention trials. PMID:28469088

Initial Assessment of β3-Adrenoceptor-Activated Brown Adipose Tissue in Streptozotocin-Induced Type 1 Diabetes Rodent Model Using [18F]Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

PubMed

Baranwal, Aparna; Mirbolooki, M Reza; Mukherjee, Jogeshwar

2015-01-01

Metabolic activity of brown adipose tissue (BAT) is activated by β3-adrenoceptor agonists and norepinephrine transporter (NET) blockers and is measurable using [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) in rats. Using the streptozotocin (STZ)-treated rat model of type 1 diabetes mellitus (T1DM), we investigated BAT activity in this rat model under fasting and nonfasting conditions using [(18)F]FDG PET/CT. Drugs that enhance BAT activity may have a potential for therapeutic development in lowering blood sugar in insulin-resistant diabetes. Rats were rendered diabetic by administration of STZ and confirmed by glucose measures. [(18)F]FDG was injected in the rats (fasted or nonfasted) pretreated with either saline or β3-adrenoceptor agonist CL316,243 or the NET blocker atomoxetine for PET/CT scans. [(18)F]FDG metabolic activity was computed as standard uptake values (SUVs) in interscapular brown adipose tissue (IBAT) and compared across the different drug treatment conditions. Blood glucose levels > 500 mg/dL were established for the STZ-treated diabetic rats. Under fasting conditions, average uptake of [(18)F]FDG in the IBAT of STZ-treated diabetic rats was approximately 70% lower compared to that of normal rats. Both CL316,243 and atomoxetine activated IBAT in normal rats had an SUV > 5, whereas activation in STZ-treated rats was significantly lower. The agonist CL316,243 activated IBAT up to threefold compared to saline in the fasted STZ-treated rat. In the nonfasted rat, the IBAT activation was up by twofold by CL316243. Atomoxetine had a greater effect on lowering blood sugar levels compared to CL316,243 in the nonfasted rats. A significant reduction in metabolic activity was observed in the STZ-treated diabetic rodent model. Increased IBAT activity in the STZ-treated diabetic rat under nonfasted conditions using the β3-adrenoceptor agonist CL316,243 suggests a potential role of BAT in modulating blood

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

PubMed

Muoio, Barbara; Giovanella, Luca; Treglia, Giorgio

2017-11-23

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

Regional 18F-Fluorodeoxyglucose Hypometabolism is Associated with Higher Apathy Scores Over Time in Early Alzheimer Disease.

PubMed

Gatchel, Jennifer R; Donovan, Nancy J; Locascio, Joseph J; Becker, J Alex; Rentz, Dorene M; Sperling, Reisa A; Johnson, Keith A; Marshall, Gad A

2017-07-01

Apathy is among the earliest and most pervasive neuropsychiatric symptoms in prodromal and mild Alzheimer disease (AD) dementia that correlates with functional impairment and disease progression. We investigated the association of apathy with regional 18F-fluorodeoxyglucose (FDG) metabolism in cognitively normal, mild cognitive impairment, and AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative database. Cross-sectional and longitudinal studies. 57 North American research sites. 402 community dwelling elders. Apathy was assessed using the Neuropsychiatric Inventory Questionnaire. Baseline FDG metabolism in five regions implicated in the neurobiology of apathy and AD was investigated in relationship to apathy at baseline (cross-sectional general linear model) and longitudinally (mixed random/fixed effect model). Covariates included age, sex, diagnosis, apolipoprotein E genotype, premorbid intelligence, cognition, and antidepressant use. Cross-sectional analysis revealed that posterior cingulate hypometabolism, diagnosis, male sex, and antidepressant use were associated with higher apathy scores. Longitudinal analysis revealed that the interaction of supramarginal hypometabolism and time, posterior cingulate hypometabolism, and antidepressant use were associated with higher apathy scores across time; only supramarginal hypometabolism was positively related to rate of increase of apathy. Results support an association of apathy with hypometabolism in parietal regions commonly affected in early stages of AD, rather than medial frontal regions implicated in the neurobiology of apathy in later stages. Further work is needed to substantiate whether this localization is specific to apathy rather than to disease stage, and to investigate the potential role of AD proteinopathies in the pathogenesis of apathy. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

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

Cui, Yi; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo; Song, Jie

Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162more » robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e

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

PubMed

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

2017-12-01

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

Comparison of the biological effects of {sup 18}F at different intracellular levels

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

Kashino, Genro, E-mail: kashino@oita-u.ac.jp; Hayashi, Kazutaka; Douhara, Kazumasa

Highlights: • We estimated the inductions of DNA DSB in cell treated with {sup 18}F-FDG. • We found that inductions of DNA DSB are dependent on accumulation of {sup 18}F in cell. • Accumulation of {sup 18}F in cell may be indispensable for risk estimation of PET. - Abstract: We herein examined the biological effects of cells treated with {sup 18}F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of {sup 18}F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with twomore » types of {sup 18}F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with {sup 18}F-FDG than in those treated with {sup 18}F-HF. The clonogenic survival of cells was significantly lower with {sup 18}F-FDG than with {sup 18}F-HF. We concluded that the efficient accumulation of {sup 18}F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.« less

Brain and Brown Adipose Tissue Metabolism in Transgenic Tg2576 Mice Models of Alzheimer Disease Assessed Using 18F-FDG PET Imaging

PubMed Central

Coleman, Robert A.; Liang, Christopher; Patel, Rima; Ali, Sarah

2017-01-01

Objective: Imaging animal models of Alzheimer disease (AD) is useful for the development of therapeutic drugs and understanding AD. Transgenic Swedish hAPPswe Tg2576 mice are a good model of β-amyloid plaques. We report 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of brain and intrascapular brown adipose tissue (IBAT) in transgenic mice 2576 (Tg2576) and wild-type (WT) mice. Methods: Transgenic Tg2576 mice and WT mice, >18 months were injected intraperitonally with ≈ 25 to 30 MBq 18F-FDG while awake. After 60 minutes, they were anesthetized with isoflurane (2.5%) and imaged with Inveon MicroPET. Select mice were killed, imaged ex vivo, and 20 µm sections cut for autoradiography. 18F-FDG uptake in brain and IBAT PET and brain autoradiographs were analyzed. Results: Fasting blood glucose levels averaged 120 mg/dL for WT and 100 mg/dL for Tg2576. Compared to WT, Tg2576 mice exhibited a decrease in SUVglc in the various brain regions. Average reductions in the cerebrum regions were as high as −20%, while changes in cerebellum were −3%. Uptake of 18F-FDG in IBAT decreased by −60% in Tg2576 mice and was found to be significant. Intrascapular brown adipose tissue findings in Tg2576 mice are new and not previously reported. Use of blood glucose for PET data analysis and corpus callosum as reference region for autoradiographic analysis were important to detect change in Tg2576 mice. Conclusion: Our results suggest that 18F-FDG uptake in the Tg2576 mice brain show 18F-FDG deficits only when blood glucose is taken into consideration. PMID:28654383

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2003-12-01

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

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

PubMed

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

2016-04-01

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

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

PubMed Central

Riss, Patrick J; Hong, Young T; Williamson, David; Caprioli, Daniele; Sitnikov, Sergey; Ferrari, Valentina; Sawiak, Steve J; Baron, Jean-Claude; Dalley, Jeffrey W; Fryer, Tim D; Aigbirhio, Franklin I

2011-01-01

The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats. PMID:21750562

Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study.

PubMed

Klenk, Christopher; Gawande, Rakhee; Uslu, Lebriz; Khurana, Aman; Qiu, Deqiang; Quon, Andrew; Donig, Jessica; Rosenberg, Jarrett; Luna-Fineman, Sandra; Moseley, Michael; Daldrup-Link, Heike E

2014-03-01

Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ

Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

PubMed

Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

2013-12-01

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

Evaluation of D-isomers of 4-borono-2-18F-fluoro-phenylalanine and O-11C-methyl-tyrosine as brain tumor imaging agents: a comparative PET study with their L-isomers in rat brain glioma.

PubMed

Kanazawa, Masakatsu; Nishiyama, Shingo; Hashimoto, Fumio; Kakiuchi, Takeharu; Tsukada, Hideo

2018-06-13

The potential of the D-isomerization of 4-borono-2- 18 F-fluoro-phenylalanine ( 18 F-FBPA) to improve its target tumor to non-target normal brain tissue ratio (TBR) was evaluated in rat brain glioma and compared with those of L- and D- 11 C-methyl-tyrosine ( 11 C-CMT). The L- or D-isomer of 18 F-FBPA was injected into rats through the tail vein, and their whole body kinetics and distributions were assessed using the tissue dissection method up to 90 min after the injection. The kinetics of L- and D- 18 F-FBPA or L- and D- 11 C-CMT in the C-6 glioma-inoculated rat brain were measured for 90 or 60 min, respectively, using high-resolution animal PET, and their TBRs were assessed. Tissue dissection analyses showed that D- 18 F-FBPA uptake was significantly lower than that of L- 18 F-FBPA in the brain and abdominal organs, except for the kidney and bladder, reflecting the faster elimination rate of D- 18 F-FBPA than L- 18 F-FBPA from the blood to the urinary tract. PET imaging using 18 F-FBPA revealed that although the brain uptake of D- 18 F-FBPA was significantly lower than that of L- 18 F-FBPA, the TBR of the D-isomer improved to 6.93 from 1.45 for the L-isomer. Similar results were obtained with PET imaging using 11 C-CMT with a smaller improvement in TBR to 1.75 for D- 11 C-CMT from 1.33 for L- 11 C-CMT. The present results indicate that D- 18 F-FBPA is a better brain tumor imaging agent with higher TBR than its original L-isomer and previously reported tyrosine-based PET imaging agents. This improved TBR of D- 18 F-FBPA without any pre-treatments, such as tentative blood-brain barrier disruption using hyperosmotic agents or sonication, suggests that the D-isomerization of BPA results in the more selective accumulation of 10 B in tumor cells that is more effective and less toxic than conventional L-BPA.

Tumor heterogeneity measured on F-18 fluorodeoxyglucose positron emission tomography/computed tomography combined with plasma Epstein-Barr Virus load predicts prognosis in patients with primary nasopharyngeal carcinoma.

PubMed

Chan, Sheng-Chieh; Chang, Kai-Ping; Fang, Yu-Hua Dean; Tsang, Ngan-Ming; Ng, Shu-Hang; Hsu, Cheng-Lung; Liao, Chun-Ta; Yen, Tzu-Chen

2017-01-01

Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC. Retrospective cohort study. We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features. The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001). Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity. 4 Laryngoscope, 127:E22-E28, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by 19F chemical shift imaging

PubMed Central

Coman, Daniel; Sanganahalli, Basavaraju G.; Cheng, David; McCarthy, Timothy; Rothman, Douglas L.; Hyder, Fahmeed

2014-01-01

19F magnetic resonance spectroscopy (MRS) studies of 2-fluoro-2-deoxy-D-glucose (FDG) and 2-fluoro-2-deoxy-D-glucose-6-phosphate (FDG-6P) can be used for directly assessing total glucose metabolism in vivo. To date, 19F MRS measurements of FDG phosphorylation in the brain have either been achieved ex vivo from extracted tissue or in vivo by unusually long acquisition times. Electrophysiological and functional magnetic resonance imaging (fMRI) measurements indicate that FDG doses up to 500mg/kg can be tolerated with minimal side effects on cerebral physiology and evoked fMRI-BOLD responses to forepaw stimulation. In halothane-anesthetized rats, we report localized in vivo detection and separation of FDG and FDG-6P MRS signals with 19F 2D chemical shift imaging (CSI) at 11.7T. A metabolic model based on reversible transport between plasma and brain tissue, which included a non-saturable plasma to tissue component, was used to calculate spatial distribution of FDG and FDG-6P concentrations in rat brain. In addition, spatial distribution of rate constants and metabolic fluxes of FDG to FDG-6P conversion were estimated. Mapping the rate of FDG to FDG-6P conversion by 19F CSI provides an MR methodology that could impact other in vivo applications such as characterization of tumor pathophysiology. PMID:24581725

No-carrier-added (18F)-N-methylspiroperidol

DOEpatents

Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

1993-01-01

There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

No-carrier-added (18F)-N-methylspiroperidol

DOEpatents

Shiue, Chyng-Yann; Fowler, Joanna S.; Wolf, Alfred P.

1993-07-06

There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

The value of (18) F-fluorodeoxyglucose positron emission tomography for prediction of treatment response in gastrointestinal stromal tumors: a systematic review and meta-analysis.

PubMed

Hassanzadeh-Rad, Arman; Yousefifard, Mahmoud; Katal, Sanaz; Asady, Hadi; Fard-Esfahani, Armaghan; Moghadas Jafari, Ali; Hosseini, Mostafa

2016-05-01

Early detection of response to treatment is critically important in gastrointestinal stromal tumors (GIST). Therefore, the present systematic review and meta-analysis assessed the value of (18) f-fluorodeoxyglucose positron emission tomography ((18) FDG-PET) on prediction of therapeutic response of GIST patients to systemic treatments. The literature search was conducted using PubMed, SCOPUS, Cochrane, and Google Scholar databases, and review article references. Eligible articles were defined as studies included confirmed GIST patients who underwent (18) FDG-PET as well as assessing the screening role of it. Finally, 21 relevant articles were included. The analysis showed the pooled sensitivity and specificity of 18FDG-PET in evaluation of response to treatment of GIST patient were 0.90 (95% CI: 0.85-0.94; I(2)  = 52.59, P = 0.001) and 0.62 (95% CI: 0.49-0.75; I(2)  = 69.7, P = 0.001), respectively. In addition, the pooled prognostic odds ratio of (18) FDG-PET for was 14.99 (95% CI, 6.42-34.99; I(2)  = 100.0, P < 0.001). The Meta regression showed that sensitivity of (18) FDG-PET was higher if the sample size of study was equal or more than 30 cases (sensitivity = 0.93; 95% CI: 0.89-0.97), when using PET/CT (sensitivity = 0.92; 95% CI: 0.89-0.97), and self-design criteria (sensitivity = 0.93; 95% CI: 0.87-1.0). The present meta-analysis showed (18) FDG-PET has a significant value in predicting treatment response in GIST patients. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma.

PubMed

Chalaye, Julia; Costentin, Charlotte E; Luciani, Alain; Amaddeo, Giuliana; Ganne-Carrié, Nathalie; Baranes, Laurence; Allaire, Manon; Calderaro, Julien; Azoulay, Daniel; Nahon, Pierre; Seror, Olivier; Mallat, Ariane; Soussan, Michael; Duvoux, Christophe; Itti, Emmanuel; Nault, Jean Charles

2018-03-06

Hepatocellular carcinoma (HCC) staging according to the Barcelona Clinical Liver Cancer (BCLC) classification is based on conventional imaging. The aim of our study was to assess the impact of dual-tracer 18F-fluorocholine and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on tumor staging and treatment allocation. A total of 192 dual-tracer PET/CT scans (18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT) were performed in 177 patients with HCC. BCLC staging and treatment proposal were retrospectively collected based on conventional imaging, along with any new lesions detected, and changes in BCLC classification or treatment allocation based on dual-tracer PET/CT. Patients were primarily men (87.5%) with cirrhosis (71%) due to alcohol ± non-alcoholic steatohepatitis (26%), viral infection (62%) or unknown causes (12%). Among 122 patients with PET/CT performed for staging, BCLC stage based on conventional imaging was 0/A in 61 patients (50%), B in 32 patients (26%) and C in 29 patients (24%). Dual-tracer PET/CT detected new lesions in 26 patients (21%), upgraded BCLC staging in 14 (11%) and modified treatment strategy in 17 (14%). In addition, dual-tracer PET/CT modified the final treatment in 4/9 (44%) patients with unexplained elevation of alpha-fetoprotein (AFP), 10/25 patients (40%) with doubtful lesions on conventional imaging and 3/36 patients (8%) waiting for liver transplantation without active HCC after tumor response following bridging therapy. When used for HCC staging, dual-tracer PET/CT enabled BCLC upgrading and treatment modification in 11% and 14% of patients, respectively. Dual-tracer PET/CT might also be useful in specific situations (an unexplained rise in AFP, doubtful lesions or pre-transplant evaluation of patients without active HCC). Using a combination of tracers 18F-fluorocholine and 18F-fluorodeoxyglucose when performing positron emission tomography/computed tomography (PET/CT), often called a PET

18F-FDG avid Sclerosing Angiomatoid Nodular Transformation (SANT) of spleen on PET-CT - a rare mimicker of metastasis.

PubMed

Sharma, Punit

2018-01-01

Sclerosing Angiomatoid Nodular Transformation (SANT) is a rare benign vascular tumor of spleen. It consists of multiple angiomatoid nodules surrounded by dense fibrous tissue that often coalesces centrally to form a scar, which is considered to be a characteristic feature. These are usually asymptomatic and incidentally detected on imaging for other underlying pathology. SANTs can be 18F-Fluorodeoxyglucose (18F-FDG) avid on positron emission tomography-computed tomography (PET-CT) and thus can lead to false positive finding in oncological patients.

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

PubMed

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

2018-06-01

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

Volume-Based Parameters of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Disease Recurrence Prediction in Postmastectomy Breast Cancer Patients With 1 to 3 Positive Axillary Lymph Nodes

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

Nakajima, Naomi, E-mail: haruhi0321@gmail.com; Department of Radiology, Ehime University, Ehime; Kataoka, Masaaki

Purpose: To determine whether volume-based parameters on pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography in breast cancer patients treated with mastectomy without adjuvant radiation therapy are predictive of recurrence. Methods and Materials: We retrospectively analyzed 93 patients with 1 to 3 positive axillary nodes after surgery, who were studied with {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography for initial staging. We evaluated the relationship between positron emission tomography parameters, including the maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), and clinical outcomes. Results: The median follow-up duration was 45 months. Recurrence was observed in 11 patients.more » Metabolic tumor volume and TLG were significantly related to tumor size, number of involved nodes, nodal ratio, nuclear grade, estrogen receptor (ER) status, and triple negativity (TN) (all P values were <.05). In receiver operating characteristic curve analysis, MTV and TLG showed better predictive performance than tumor size, ER status, or TN (area under the curve: 0.85, 0.86, 0.79, 0.74, and 0.74, respectively). On multivariate analysis, MTV was an independent prognostic factor of locoregional recurrence-free survival (hazard ratio 34.42, 95% confidence interval 3.94-882.71, P=.0008) and disease-free survival (DFS) (hazard ratio 13.92, 95% confidence interval 2.65-103.78, P=.0018). The 3-year DFS rate was 93.8% for the lower MTV group (<53.1; n=85) and 25.0% for the higher MTV group (≥53.1; n=8; P<.0001, log–rank test). The 3-year DFS rate for patients with both ER-positive status and MTV <53.1 was 98.2%; and for those with ER-negative status and MTV ≥53.1 it was 25.0% (P<.0001). Conclusions: Volume-based parameters improve recurrence prediction in postmastectomy breast cancer patients with 1 to 3 positive nodes. The addition of MTV to ER status or TN has

Metabolic monitoring of advanced uterine cervical cancer neoadjuvant chemotherapy by using [F-18]-Fluorodeoxyglucose positron emission tomography: preliminary results in three patients.

PubMed

Yoshida, Yoshio; Kurokawa, Tetsuji; Kawahara, Kazumi; Yagihara, Akira; Tsuchida, Tatsuro; Okazawa, Hidehiko; Fujibayashi, Yasuhisa; Yonekura, Yoshiharu; Kotsuji, Fumikazu

2004-12-01

The aim of this report is to describe the potential clinical utility of tracer [F-18]-Fluorodeoxyglucose (FDG) uptake, quantitated as a standardized uptake value (SUV) by positron emission tomography (PET), to evaluate treatment response to neoadjuvant chemotherapy (NAC) in advanced uterine cervical cancer. We briefly describe the clinical courses of three women with advanced cervical cancer who were treated with neoadjuvant chemotherapy (NAC) prior to radical hysterectomy and who were analyzed for correlation with the decrease in tumor volume by magnetic resonance imaging (MRI), in SUV by FDG-PET, and by histologic response. In these individuals, tumor volume and SUV were decreased by NAC. The decrease in SUV by FDG-PET was better correlated to histologic response for NAC than MRI was in advanced cervical cancer. Measurement of SUV by FDG-PET has clinical utility in evaluating treatment response for NAC in advanced cervical cancer. Although work in this field is still in the early stages, this report demonstrates that SUV by FDG-PET has the potential to become the new standard for monitoring the treatment response of NAC in cervical cancer. This monitoring approach must be proven in a larger number of patients for both primary and secondary lesions and should be further explored in another gynecologic cancer.

Usefulness of esophagogastroduodenoscopy and 18F-fluorodeoxyglucose positron-emission tomography in detecting synchronous multiple primary cancers with oral cancer.

PubMed

Ishibashi-Kanno, Naomi; Yamagata, Kenji; Uchida, Fumihiko; Hasegawa, Shogo; Yanagawa, Toru; Bukawa, Hiroki

2017-12-01

The purpose of this study is to compare the value of screening for synchronous multiple primary cancers in other organs by esophagogastroduodenoscopy (EGD) or 18 F-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients newly diagnosed with oral cancer. We retrospectively examined consecutive Japanese patients who were diagnosed with oral squamous cell carcinoma (OSCC) and were screened for synchronous multiple primary cancers in other organs by EGD and/or PET-CT between January 2010 and December 2015 at our institution. The study included 190 patients (106 males and 84 females) from 36 to 93 years of age (median age 68.8 years). The patients were screened by EGD, PET-CT, or both before beginning treatment for OSCC. Of 190 Japanese patients with OSCC, 15 had multiple primary cancers: 13 patients had double cancer and two had triple cancers. The sites of the 17 multiple primary cancers were gastric (6), esophageal (4), and lung (3), and ovarian, colon, liver, and thyroid (1 each). All of the gastric and esophageal cancers were found by EGD and were not detected by PET-CT. For three patients, the detection of multiple cancers affected the treatment modality or order of treatment selected for the OSCC. In two cases, the oral cancer and multiple primary cancer(s) in another organ were resected simultaneously by joint surgical teams. PET-CT for oral cancer patients is an effective supporting diagnostic tool. However, the ability of PET-CT has some limitations. Especially for early detection of the upper gastrointestinal cancers, it is necessary to be supplemented by EGD.

Impact of 18F-fluorodeoxyglucose positron emission tomography before and after definitive radiation therapy in patients with apparently solitary plasmacytoma.

PubMed

Kim, Paul J; Hicks, Rodney J; Wirth, Andrew; Ryan, Gail; Seymour, John F; Prince, H Miles; Mac Manus, Michael P

2009-07-01

To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.

Diagnostic utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in asymptomatic subjects at increased risk for Alzheimer's disease.

PubMed

Drzezga, Alexander; Altomare, Daniele; Festari, Cristina; Arbizu, Javier; Orini, Stefania; Herholz, Karl; Nestor, Peter; Agosta, Federica; Bouwman, Femke; Nobili, Flavio; Walker, Zuzana; Frisoni, Giovanni Battista; Boccardi, Marina

2018-05-13

To assess the clinical utility of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of early signs of neurodegeneration in conditions of increased risk for Alzheimer's disease (AD) as defined by: subjective cognitive decline (SCD), evidence of cerebral amyloid-pathology, apolipoprotein E (APOE) ε4-positive genotype, or autosomal dominant forms of AD (ADAD) in asymptomatic stages. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted using the Delphi method on three different diagnostic scenarios. The level of empirical study evidence for the use of FDG-PET to detect meaningful early signs of neurodegeneration was considered to be poor for ADAD and lacking for SCD and asymptomatic persons at risk, based on APOE ε4-positive genotype or cerebral amyloid pathology. Consequently, and consistent with current diagnostic criteria, panelists decided not to recommend routine clinical use of FDG-PET in these situations and to currently mainly reserve it for research purposes. Currently, there is limited evidence on which to base recommendations regarding the clinical routine use of FDG-PET to detect diagnostically meaningful early signs of neurodegeneration in asymptomatic subjects with ADAD, with APOE ε4-positive genotype, or with cerebral amyloid pathology, and in subjects with SCD. Future prospective studies are warranted and in part already ongoing, aiming to assess the added value of FDG-PET in this context beyond research applications.

Role of computed tomography and [18F] fluorodeoxyglucose positron emission tomography image fusion in conformal radiotherapy of non-small cell lung cancer: a comparison with standard techniques with and without elective nodal irradiation.

PubMed

Ceresoli, Giovanni Luca; Cattaneo, Giovanni Mauro; Castellone, Pietro; Rizzos, Giovanna; Landoni, Claudio; Gregorc, Vanesa; Calandrino, Riccardo; Villa, Eugenio; Messa, Cristina; Santoro, Armando; Fazio, Ferruccio

2007-01-01

Mediastinal elective node irradiation (ENI) in patients with non-small cell lung cancer candidate to radical radiotherapy is controversial. In this study, the impact of co-registered [18F]fluorodeoxyglucose-positron emission tomography (PET) and standard computed tomography (CT) on definition of target volumes and toxicity parameters was evaluated, by comparison with standard CT-based simulation with and without ENI. CT-based gross tumor volume (GTVCT) was first contoured by a single observer without knowledge of PET results. Subsequently, the integrated GTV based on PET/CT coregistered images (GTVPET/CT) was defined. Each patient was planned according to three different treatment techniques: 1) radiotherapy with ENI using the CT data set alone (ENI plan); 2) radiotherapy without ENI using the CT data set alone (no ENI plan); 3) radiotherapy without ENI using PET/CT fusion data set (PET plan). Rival plans were compared for each patient with respect to dose to the normal tissues (spinal cord, healthy lungs, heart and esophagus). The addition of PET-modified TNM staging in 10/21 enrolled patients (48%); 3/21 were shifted to palliative treatment due to detection of metastatic disease or large tumor not amenable to high-dose radiotherapy. In 7/18 (39%) patients treated with radical radiotherapy, a significant (> or =25%) change in volume between GTVCT and GTVPET/CT was observed. For all the organs at risk, ENI plans had dose values significantly greater than no-ENI and PET plans. Comparing no ENI and PET plans, no statistically significant difference was observed, except for maximum point dose to the spinal cord Dmax, which was significantly lower in PET plans. Notably, even in patients in whom PET/CT planning resulted in an increased GTV, toxicity parameters were fairly acceptable, and always more favorable than with ENI plans. Our study suggests that [18F]-fluorodeoxyglucose-PET should be integrated in no-ENI techniques, as it improves target volume delineation

Radiation injury vs. recurrent brain metastasis: combining textural feature radiomics analysis and standard parameters may increase 18F-FET PET accuracy without dynamic scans.

PubMed

Lohmann, Philipp; Stoffels, Gabriele; Ceccon, Garry; Rapp, Marion; Sabel, Michael; Filss, Christian P; Kamp, Marcel A; Stegmayr, Carina; Neumaier, Bernd; Shah, Nadim J; Langen, Karl-Josef; Galldiks, Norbert

2017-07-01

We investigated the potential of textural feature analysis of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-FET) PET to differentiate radiation injury from brain metastasis recurrence. Forty-seven patients with contrast-enhancing brain lesions (n = 54) on MRI after radiotherapy of brain metastases underwent dynamic 18 F-FET PET. Tumour-to-brain ratios (TBRs) of 18 F-FET uptake and 62 textural parameters were determined on summed images 20-40 min post-injection. Tracer uptake kinetics, i.e., time-to-peak (TTP) and patterns of time-activity curves (TAC) were evaluated on dynamic PET data from 0-50 min post-injection. Diagnostic accuracy of investigated parameters and combinations thereof to discriminate between brain metastasis recurrence and radiation injury was compared. Diagnostic accuracy increased from 81 % for TBR mean alone to 85 % when combined with the textural parameter Coarseness or Short-zone emphasis. The accuracy of TBR max alone was 83 % and increased to 85 % after combination with the textural parameters Coarseness, Short-zone emphasis, or Correlation. Analysis of TACs resulted in an accuracy of 70 % for kinetic pattern alone and increased to 83 % when combined with TBR max . Textural feature analysis in combination with TBRs may have the potential to increase diagnostic accuracy for discrimination between brain metastasis recurrence and radiation injury, without the need for dynamic 18 F-FET PET scans. • Textural feature analysis provides quantitative information about tumour heterogeneity • Textural features help improve discrimination between brain metastasis recurrence and radiation injury • Textural features might be helpful to further understand tumour heterogeneity • Analysis does not require a more time consuming dynamic PET acquisition.

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

PubMed Central

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

2017-01-01

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

The influence of interpreters' professional background and experience on the interpretation of multimodality imaging of pulmonary lesions using 18F-3'-deoxy-fluorothymidine and 18F-fluorodeoxyglucose PET/CT.

PubMed

Xu, Bai-xuan; Liu, Chang-bin; Wang, Rui-min; Shao, Ming-zhe; Fu, Li-ping; Li, Yun-gang; Tian, Jia-he

2013-01-01

Based on the results of a recently accomplished multicenter clinical trial for the incremental value of a dual-tracer (18F-FDG and 18F-FLT), dual-modality (PET and CT) imaging in the differential diagnosis of pulmonary lesions, we investigate some issues that might affect the image interpretation and result reporting. The images were read in two separate sessions. Firstly the images were read and reported by physician(s) of the imaging center on completion of each PET/CT scanning. By the end of MCCT, all images collected during the trial were re-read by a collective of readers in an isolated, blinded, and independent way. One hundred sixty two patients successfully passed the data verification and entered into the final analysis. The primary reporting result showed adding 18F-FDG image information did not change the clinical performance much in sensitivity, specifity and accuracy, but the ratio between SUVFLT and SUVFDG did help the differentiation efficacy among the three subgroups of patients. The collective reviewing result showed the diagnostic achievement varied with reading strategies. ANOVA indicated significant differences among (18)F-FDG, (18)F-FLT in SUV (F = 14.239, p = 0.004). CT had almost the same diagnostic performance as 18F-FLT. When the 18F-FDG, 18F-FLT and CT images read in pair, both diagnostic sensitivity and specificity improved. The best diagnostic figures were obtained in full-modality strategy, when dual-tracer PET worked in combination with CT. With certain experience and training both radiologists and nuclear physicians are qualified to read and to achieve the similar diagnostic accuracy in PET/CT study. Making full use of modality combination and selecting right criteria seems more practical than professional back ground and personal experience in the new hybrid imaging technology, at least when novel tracer or application is concerned.

Usefulness of CA125 and their kinetic parameters and positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose ([18F] FDG) in the detection of recurrent ovarian cancer levels.

PubMed

Palomar Muñoz, Azahara; Cordero García, José Manuel; Talavera Rubio, Prado; García Vicente, Ana M; González García, Beatriz; Bellón Guardia, María Emiliana; Soriano Castrejón, Ángel; Aranda Aguilar, Enrique

2017-12-21

To assess the usefulness of cancer antigen 125 (CA125) serum levels and kinetic values, velocity (CA125vel) and doubling time (CA125dt), as well as fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT), in the detection of ovarian cancer recurrence. To assess the optimal cut-off for CA125, CA125vel and CA125dt to detect relapse with [ 18 F]FDG-PET/CT. A retrospective analysis was performed of 59 [ 18 F]FDG-PET/CT (48 patients) for suspected recurrence of ovarian cancer. Receiver operating characteristic (ROC) curves were plotted and area-under-the curve (AUC) statistics were computed for CA125, CA125vel and CA125dt. The results obtained in the group with normal and high (>35U/ml) CA125 levels were compared. Forty-four cases of recurrence were diagnosed (7 had CA125 ≤35U/ml), whereas 15 showed no disease. All of them were correctly catalogued by PET/CT. In ROC analysis, the discriminatory power of CA125 was relatively high (AUC 0.835) and the optimal cut-off point to reflect active disease was 23.9U/ml. The ROC analyses for the CA125vel and CA125dt showed an AUC of 0.849 and 0.728, respectively, with an optimal cut-off point of 1.96U/ml/month and 0.76 months, respectively. In patients with normal CA125 and recurrence of ovarian cancer, the CA125vel was significantly higher than in patients without recurrence (p=0.029). [ 18 F]FDG-PET/CT is more accurate than CA125 parameters in the detection of ovarian cancer recurrence. CA125 serum levels are essential; nevertheless, CA125 kinetic values must be considered to detect relapse. Particularly in patients with CA125 within normal values, in which a higher CA125vel is indicative of recurrence. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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

PubMed

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

2012-03-01

Activation of microglia is a hallmark of inflammatory, infectious, and degenerative diseases of the central nervous system. Several studies have indicated that there is an increase in release of β-glucuronidase by activated microglia into the extracellular space at the site of neuroinflammation. β-glucuronidase is involved in the hydrolysis of glycosaminoglycans on the cell surface and the degradation of the extracellular matrix. Therefore, β-glucuronidase might be a biomarker for ongoing neurodegeneration induced by neuroinflammation. In this study, we investigated whether the PET tracer (18)F-FEAnGA was able to detect β-glucuronidase release during neuroinflammation in a rat model of herpes encephalitis. Male Wistar rats were intranasally inoculated with herpes simplex virus 1 (HSV-1) or phosphate-buffered saline as a control. (11)C-(R)-PK11195 and (18)F-FEAnGA small-animal PET scans were acquired for 60 min. Logan graphical analysis was used to calculate (18)F-FEAnGA distribution volumes (DV(Logan)) in various brain areas. After administration of (18)F-FEAnGA, the area under the activity concentration-versus-time curve of the whole brain was 2 times higher in HSV-1-infected rats than in control rats. In addition, the DV(Logan) of (18)F-FEAnGA was most increased in the frontopolar cortex, frontal cortex, bulbus olfactorius, cerebral cortex, cerebellum, and brainstem of HSV-1-infected rats, when compared with control rats. The conversion of (18)F-FEAnGA to 4-hydroxy-3-nitrobenzyl alcohol was found to be 1.6 times higher in HSV-1-infected rats than in control rats and correlated with the DV(Logan) of (18)F-FEAnGA in the same areas of the brain. Furthermore, the DV(Logan) of (18)F-FEAnGA also correlated with β-glucuronidase activity in the same brain regions. In addition, DV(Logan) of (18)F-FEAnGA showed a tendency to correlate with (11)C-(R)-PK11195 uptake (marker for activated microglia) in the same brain regions. Despite relatively low brain uptake, (18)F

Imaging grafted cells with [18F]FHBG using an optimized HSV1-TK mammalian expression vector in a brain injury rodent model.

PubMed

Salabert, Anne-Sophie; Vaysse, Laurence; Beaurain, Marie; Alonso, Mathieu; Arribarat, Germain; Lotterie, Jean-Albert; Loubinoux, Isabelle; Tafani, Mathieu; Payoux, Pierre

2017-01-01

Cell transplantation is an innovative therapeutic approach after brain injury to compensate for tissue damage. To have real-time longitudinal monitoring of intracerebrally grafted cells, we explored the feasibility of a molecular imaging approach using thymidine kinase HSV1-TK gene encoding and [18F]FHBG as a reporter probe to image enzyme expression. A stable neuronal cell line expressing HSV1-TK was developed with an optimised mammalian expression vector to ensure long-term transgene expression. After [18F]FHBG incubation under defined parameters, calibration ranges from 1 X 104 to 3 X 106 Neuro2A-TK cells were analysed by gamma counter or by PET-camera. In parallel, grafting with different quantities of [18F]FHBG prelabelled Neuro2A-TK cells was carried out in a rat brain injury model induced by stereotaxic injection of malonate toxin. Image acquisition of the rats was then performed with PET/CT camera to study the [18F]FHBG signal of transplanted cells in vivo. Under the optimised incubation conditions, [18F]FHBG cell uptake rate was around 2.52%. In-vitro calibration range analysis shows a clear linear correlation between the number of cells and the signal intensity. The PET signal emitted into rat brain correlated well with the number of cells injected and the number of surviving grafted cells was recorded via the in-vitro calibration range. PET/CT acquisitions also allowed validation of the stereotaxic injection procedure. Technique sensitivity was evaluated under 5 X 104 grafted cells in vivo. No [18F]FHBG or [18F]metabolite release was observed showing a stable cell uptake even 2 h post-graft. The development of this kind of approach will allow grafting to be controlled and ensure longitudinal follow-up of cell viability and biodistribution after intracerebral injection.

Imaging of amyloid deposition in human brain using positron emission tomography and [18F]FACT: comparison with [11C]PIB.

PubMed

Ito, Hiroshi; Shinotoh, Hitoshi; Shimada, Hitoshi; Miyoshi, Michie; Yanai, Kazuhiko; Okamura, Nobuyuki; Takano, Harumasa; Takahashi, Hidehiko; Arakawa, Ryosuke; Kodaka, Fumitoshi; Ono, Maiko; Eguchi, Yoko; Higuchi, Makoto; Fukumura, Toshimitsu; Suhara, Tetsuya

2014-04-01

The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The (18)F-labeled amyloid tracer, [(18)F]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [(11)C]Pittsburgh compound B (PIB) and [(18)F]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared. Two PET scans, one of each with [(11)C]PIB and [(18)F]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation. No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [(18)F]FACT studies without partial volume correction, while significant differences were observed in [(11)C]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [(18)F]FACT studies as well as [(11)C]PIB. Relatively lower uptakes of [(11)C]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [(18)F]FACT. Relatively higher uptake of [(11)C]PIB in distribution was observed in the frontal and parietal cortices. Since [(18)F]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [(11)C]PIB and [(18)F]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the

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

PubMed

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

2016-11-01

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

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

PubMed

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

2003-06-01

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

18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.

PubMed

Thenkondar, Anuradha; Jafari, Lida; Sooriash, Robbie; Hajsadeghi, Fereshteh; Berenji, Gholam R; Li, Yuxin

2017-02-01

A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared asymptomatic on the day of the study, without any signs indicating stroke. Patient also had no known history of malignancy or cerebrovascular disease. He had mild elevation of the prostate-specific antigen level, and biopsy of his prostate was not performed. Patient had long-standing history of chronic back pain and abdominal pain. The PET bone scan demonstrated a large area of very intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke in the same area.

Radionecrosis versus disease progression in brain metastasis. Value of (18)F-DOPA PET/CT/MRI.

PubMed

Hernández Pinzón, J; Mena, D; Aguilar, M; Biafore, F; Recondo, G; Bastianello, M

2016-01-01

The use of (18)F-DOPA PET/CT with magnetic resonance imaging fusion and the use of visual methods and quantitative analysis helps to differentiate between changes post-radiosurgery vs. suspicion of disease progression in a patient with brain metastases from melanoma, thus facilitating taking early surgical action. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

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

PubMed

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

2008-06-09

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

Esophageal cancer associated with a sarcoid-like reaction and systemic sarcoidosis in lymph nodes: supportive findings of [18F]-fluorodeoxyglucose positron emission tomography-computed tomography during neoadjuvant therapy.

PubMed

Kishino, Takayoshi; Okano, Keiichi; Ando, Yasuhisa; Suto, Hironobu; Asano, Eisuke; Oshima, Minoru; Fujiwara, Masao; Usuki, Hisashi; Kobara, Hideki; Masaki, Tsutomu; Ibuki, Emi; Kushida, Yoshio; Haba, Reiji; Suzuki, Yasuyuki

2018-06-25

In patients with esophageal cancer, differentiation between lymph node metastasis and lymphadenopathies from sarcoidosis or sarcoid-like reactions of lymph nodes is clinically important. Herein, we report two esophageal cancer cases with lymph node involvement of sarcoid-like reaction or sarcoidosis. One patient received chemotherapy and the other chemoradiotherapy as initial treatments. In both cases, [ 18 F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) was performed before and after chemo(radio)therapy. After the treatment, FDG uptake was not detected in the primary tumor, but it was slightly reduced in the hilar and mediastinal lymph nodes in both cases. These non-identical responses to chemo(radio)therapy suggest the presence of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of the esophagus. Curative surgical resection was performed as treatment. These FDG-PET/CT findings may be helpful to distinguish between metastasis and sarcoidosis-associated lymphadenopathy in esophageal cancer.

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose.

PubMed

Schreckenberger, M; Gouzoulis-Mayfrank, E; Sabri, O; Arning, C; Schulz, G; Tuttass, T; Wagenknecht, G; Kaiser, H J; Sass, H; Buell, U

1998-11-01

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca's area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of

[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging.

PubMed

Marquié, Marta; Siao Tick Chong, Michael; Antón-Fernández, Alejandro; Verwer, Eline E; Sáez-Calveras, Nil; Meltzer, Avery C; Ramanan, Prianca; Amaral, Ana C; Gonzalez, Jose; Normandin, Marc D; Frosch, Matthew P; Gómez-Isla, Teresa

2017-10-01

[F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. We studied the correlation of autoradiographic binding patterns of [F-18]-AV-1451 and the stereotypical spatiotemporal pattern of progression of NFTs using legacy postmortem brain samples representing different Braak NFT stages (I-VI). We performed [F-18]-AV-1451 phosphor-screen autoradiography and quantitative tau measurements (stereologically based NFT counts and biochemical analysis of tau pathology) in three brain regions (entorhinal cortex, superior temporal sulcus and visual cortex) in a total of 22 cases: low Braak (I-II, n = 6), intermediate Braak (III-IV, n = 7) and high Braak (V-VI, n = 9). Strong and selective [F-18]-AV-1451 binding was detected in all tangle-containing regions matching precisely the observed pattern of PHF-tau immunostaining across the different Braak stages. As expected, no signal was detected in the white matter or other non-tangle containing regions. Quantification of [F-18]-AV-1451 binding was very significantly correlated with the number of NFTs present in each brain region and with the total tau and phospho-tau content as reported by Western blot and ELISA. [F-18]-AV-1451 is a promising biomarker for in vivo quantification of brain tau burden in AD. Neuroimaging-pathologic studies conducted on postmortem material from individuals imaged while alive are now needed to confirm these observations.

Primary central nervous system lymphoma with lymphomatosis cerebri in an immunocompetent child: MRI and 18F-FDG PET-CT findings.

PubMed

Jain, Tarun K; Sharma, Punit; Suman, Sudhir K C; Faizi, Nauroze A; Bal, Chandrasekhar; Kumar, Rakesh

2013-01-01

Primary central nervous system lymphoma (PCNSL) is extremely rare in immunocompetent children. We present the magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) findings of such a case in a 14-year old immunocompetent boy. In this patient, PCNSL was associated with lymphomatosis cerebri. Familiarity with the findings of this rare condition will improve the diagnostic confidence of the nuclear radiologist and avoid misdiagnosis. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.

PubMed

Li, Ping; Gui, Songbai; Cao, Lei; Gao, Hua; Bai, Jiwei; Li, Chuzhong; Zhang, Yazhuo

2016-01-01

Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.

Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects.

PubMed

Huiban, Mickael; Coello, Christopher; Wu, Kai; Xu, Yanmei; Lewis, Yvonne; Brown, Andrew P; Buraglio, Mauro; Guan, Chenbing; Shabbir, Shaila; Fong, Regan; Passchier, Jan; Rabiner, Eugenii A; Lockhart, Andrew

2017-02-01

GSK2647544 is a potent and specific inhibitor of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), which was in development as a potential treatment for Alzheimer's disease (AD). In order to refine therapeutic dose predictions and confirm brain penetration, a radiolabelled form of the inhibitor, [ 18 F]GSK2647544, was manufactured for use in a positron emission tomography (PET) biodistribution study. [ 18 F]GSK2647544 was produced using a novel, copper iodide (Cu(I)) mediated, [ 18 F]trifluoromethylation methodology. Healthy male subjects (n = 4, age range 34-42) received an oral dose of unlabelled GSK2647544 (100 mg) and after 2 h an intravenous (iv) injection of [ 18 F]GSK2647544 (average injected activity and mass were 106 ± 47 MBq and 179 ± 55 μg, respectively) followed by dynamic PET scans for 120 min. Defined regions of interest (ROI) throughout the brain were used to obtain regional time-activity curves (TACs) and compartmental modelling analysis used to estimate the primary outcome measure, whole brain volume of distribution (V T ). Secondary PK and safety endpoints were also recorded. PET dynamic data were successfully obtained from all four subjects and there were no clinically significant variations of the safety endpoints. Inspection of the TACs indicated a relatively homogenous uptake of [ 18 F]GSK2647544 across all the ROIs examined. The mean whole brain V T was 0.56 (95 % CI, 0.41-0.72). Secondary PK parameters, C max (geometric mean) and T max (median), were 354 ng/ml and 1.4 h, respectively. Metabolism of GSK2647544 was relatively consistent across subjects, with 20-40 % of the parent compound [ 18 F]GSK2647544 present after 120 min. The study provides evidence that GSK2647544 is able to cross the blood brain barrier in healthy male subjects leading to a measurable brain exposure. The administered doses of GSK2647544 were well tolerated. Exploratory modelling suggested that a twice-daily dose of 102 mg, at steady state

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

PubMed

Syed, Yahiya Y; Deeks, Emma

2015-07-01

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

Genetic and Environmental Influences on Regional Brain Uptake of 18F-FDG: A PET Study on Monozygotic and Dizygotic Twins.

PubMed

Watanabe, Shinichiro; Kato, Hiroki; Shimosegawa, Eku; Hatazawa, Jun

2016-03-01

Genetic or environmental influences on cerebral glucose metabolism are unknown. We attempted to reveal these influences in elderly twins by means of (18)F-FDG PET. (18)F-FDG uptake was studied in 40 monozygotic and 18 dizygotic volunteer twin pairs aged 30 y or over. We also created 18 control pairs by pairing age- and sex-matched genetically unrelated subjects from dizygotic and monozygotic pairs. SUV images of the brain were reconstructed and analyzed by voxel-based statistical analysis with automated region-of-interest setting. The (18)F-FDG uptake in each cerebral lobe was semiquantified by taking a ratio of SUVmean in each region of interest to whole-brain SUVaverage. We calculated an intraclass correlation coefficient of SUV ratio in each region of interest for monozygotic and dizygotic pairs. By comparing differences in coefficients between monozygotic and dizygotic pairs, genetic and environmental contributions were estimated. The intraclass correlation coefficient in monozygotic pairs was significantly higher than that in dizygotic pairs in the parietal lobes bilaterally (P < 0.001) and in the left temporal lobe (P < 0.05) but was not significantly different in other lobes. The present study indicated that in the right and left parietal lobes and left temporal lobe, cerebral glucose metabolism is influenced more by genetics than by environment, whereas in other brain regions the influence of environment is dominant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Prevalence and risk of malignancy of focal incidental uptake detected by fluorine-18-fluorodeoxyglucose positron emission tomography in the parotid gland: a meta-analysis.

PubMed

Treglia, Giorgio; Bertagna, Francesco; Sadeghi, Ramin; Muoio, Barbara; Giovanella, Luca

2015-12-01

This study aimed at performing a meta-analysis on the prevalence and risk of malignancy of focal parotid incidental uptake (FPIU) detected by hybrid fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) or (18)F-FDG PET alone. A comprehensive literature search of studies published up to July 2014 was performed. Records reporting at least 5 FPIUs were selected. Pooled prevalence and malignancy risk of FPIU were calculated including 95 % confidence intervals (95 % CI). Twelve records were selected for our meta-analysis. Pooled prevalence of FPIU detected by (18)F-FDG PET or PET/CT was 0.6 % (95 % CI 0.4-0.7 %), collecting data of 220 patients with FPIU. Overall, 181 FPIUs underwent further evaluation and 165 FPIUs were pathologically proven. Pooled risk of malignancy was 9.6 % (95 % CI 5.4-14.8 %), 10.9 % (95 % CI 5.8-17.3 %) and 20.4 % (95 % CI 12.3-30 %), considering all FPIUs detected, only those which underwent further evaluation and only those pathologically proven, respectively. Selection bias in the included studies, the heterogeneity among studies and the publication bias are limitations of our meta-analysis. Overall FPIUs are observed in about 1 % of (18)F-FDG PET or PET/CT scans and they are benign in most of the cases. Nevertheless, further evaluation is needed whenever FPIUs are detected by (18)F-FDG-PET or PET/CT to exclude malignant lesions or with possible malignant degeneration. Prospective studies are needed to confirm the findings reported by our meta-analysis.

Contrast-enhanced [18F] fluorodeoxyglucose-positron emission tomography-computed tomography as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin.

PubMed

Jain, Avani; Srivastava, Madhur Kumar; Pawaskar, Alok Suresh; Shelley, Simon; Elangovan, Indirani; Jain, Hasmukh; Pandey, Somnath; Kalal, Shilpa; Amalachandran, Jaykanth

2015-01-01

To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO). A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up. PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively. F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT.

Contrast-enhanced [18F] fluorodeoxyglucose-positron emission tomography-computed tomography as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin

PubMed Central

Jain, Avani; Srivastava, Madhur Kumar; Pawaskar, Alok Suresh; Shelley, Simon; Elangovan, Indirani; Jain, Hasmukh; Pandey, Somnath; Kalal, Shilpa; Amalachandran, Jaykanth

2015-01-01

Background: To evaluate the advantages of contrast enhanced F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-contrast enhanced CT [CECT]) when used as an initial imaging modality in patients presenting with metastatic malignancy of undefined primary origin (MUO). Materials and Methods: A total of 243 patients with fine needle aspiration cytology/biopsy proven MUO were included in this prospective study. Patients who were thoroughly evaluated for primary or primary tumor was detected by any other investigation were excluded from the analysis. Totally, 163 patients with pathological diagnosis of malignancy but no apparent sites of the primary tumor were finally selected for analysis. The site of probable primary malignancy suggested by PET-CECT was confirmed by biopsy/follow-up. Results: PET-CECT suggested probable site of primary in 128/163 (78.52%) patients. In 30/35 remaining patients, primary tumor was not detected even after extensive work-up. In 5 patients, where PET-CECT was negative, primary was found on further extensive investigations or follow-up. The sensitivity, specificity, positive predictive value and negative predictive value of the study were 95.76%, 66.67%, 88.28% and 85.71% respectively. Conclusions: F-18 FDG PET-CECT aptly serves the purpose of initial imaging modality owing to high sensitivity, negative and positive predictive value. PET-CECT not only surveys the whole body for the primary malignancy but also stages the disease accurately. Use of contrast improves the diagnostic utility of modality as well as help in staging of the primary tumor. Although benefits of using PET-CECT as initial diagnostic modality are obvious from this study, there is a need for a larger study comparing conventional methods for diagnosing primary in patients with MUO versus PET-CECT. PMID:26170563

Postinjection L-phenylalanine increases basal ganglia contrast in PET scans of 6-18F-DOPA

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

Doudet, D.J.; McLellan, C.A.; Aigner, T.G.

The sensitivity of 18F-DOPA positron emission tomography for imaging presynaptic dopamine systems is limited by the amount of specific-to-nonspecific accumulation of radioactivity in brain. In rhesus monkeys, we have been able to increase this ratio by taking advantage of the lag time between 18F-DOPA injection and the formation of its main metabolite, the amino acid 18F-fluoromethoxydopa, the entrance of which into brain is responsible for most of the brain's nonspecific radioactivity. By infusing an unlabeled amino acid, L-phenylalanine, starting 15 min after 18F-DOPA administration, we preferentially blocked the accumulation of 18F-fluoromethoxydopa by preventing its entrance into brain through competition atmore » the large neutral amino acid transport system of the blood-brain barrier. This method appears as reliable as the original and more sensitive, as demonstrated by the comparison of normal and MPTP-treated animals under both conditions.« less

Sequential [(18)F]FDG µPET whole-brain imaging of central vestibular compensation: a model of deafferentation-induced brain plasticity.

PubMed

Zwergal, Andreas; Schlichtiger, Julia; Xiong, Guoming; Beck, Roswitha; Günther, Lisa; Schniepp, Roman; Schöberl, Florian; Jahn, Klaus; Brandt, Thomas; Strupp, Michael; Bartenstein, Peter; Dieterich, Marianne; Dutia, Mayank B; la Fougère, Christian

2016-01-01

Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.

[18F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model.

PubMed

Vignal, Nicolas; Cisternino, Salvatore; Rizzo-Padoin, Nathalie; San, Carine; Hontonnou, Fortune; Gelé, Thibaut; Declèves, Xavier; Sarda-Mantel, Laure; Hosten, Benoît

2018-06-07

[ 18 F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [ 18 F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of Salmonella enterica serovar Typhimurium lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [ 18 F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min). [ 18 F]FEPPA radiosynthesis were carried out in 55 min (from EOB). The non-decay corrected radiochemical yield were 34 ± 2% ( n = 17), and the radiochemical purity greater than 99%, with a molar activity of 198 ± 125 GBq/µmol at the end of synthesis. Western blot analysis demonstrated a 2.2-fold increase in TSPO brain expression in the LPS treated mice compared to controls. This was consistent with the significant increase of [ 18 F]FEPPA brain total volume of distribution ( V T ) estimated with pharmacokinetic modelling. In conclusion, [ 18 F]FEPPA radiosynthesis was implemented with high yields. The new purification/formulation with only class 3 solvents is more suitable for in vivo studies.

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

PubMed

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

2018-05-01

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

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

PubMed

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

2017-01-01

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

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: a systematic review and a meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Zakavi, Seyed Rasoul; Caldarella, Carmelo; Muoio, Barbara; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2013-12-01

To systematically review and meta-analyse published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in osteomyelitis related to diabetic foot. A comprehensive literature search of studies on (18)F-FDG-PET and PET/CT in patients with diabetic foot was performed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) and area under the summary ROC curve of (18)F-FDG-PET and PET/CT in patients with osteomyelitis related to diabetic foot were calculated. Nine studies comprising 299 patients with diabetic foot were included in the qualitative analysis (systematic review) and discussed. The quantitative analysis (meta-analysis) of four selected studies provided the following results on a per patient-based analysis: sensitivity was 74% [95% confidence interval (95%CI): 60-85%], specificity 91% (95%CI: 85-96%), LR+ 5.56 (95%CI: 2.02-15.27), LR- 0.37 (95%CI: 0.10-1.35), and DOR 16.96 (95%CI: 2.06-139.66). The area under the summary ROC curve was 0.874. In patients with suspected osteomyelitis related to diabetic foot (18)F-FDG-PET and PET/CT demonstrated a high specificity, being potentially useful tools if combined with other imaging methods such as MRI. Nevertheless, the literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diagnostic importance of contrast enhanced (18)F-fluorodeoxyglucose positron emission computed tomography in patients with tumor induced osteomalacia: Our experience.

PubMed

Jain, Avani S; Shelley, Simon; Muthukrishnan, Indirani; Kalal, Shilpa; Amalachandran, Jaykanth; Chandran, Sureshkumar

2016-01-01

To assess the diagnostic utility of contrast-enhanced (18)F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-ceCT) in localization of tumors in patients with clinical diagnosis of tumor-induced osteomalacia (TIO), in correlation with histopathological results. Eight patients (five male and three female) aged 24-60 (mean 42) years with a clinical diagnosis of TIO were included in this prospective study. They underwent whole body (head to toe) FDG PET-ceCT following a standard protocol on Philips GEMINI TF PET-CT scanner. The FDG PET-ceCT results were correlated with postoperative histology findings and clinical follow-up. All the patients had an abnormal PET-ceCT study. The sensitivity of PET-ceCT was 87.5%, and positive predictive value was 100%. The tumor was located in the craniofacial region in 6/8 patients and in bone in 2/8 patients. Hemangiopericytoma was the most common reported histology. All patients underwent surgery, following which they demonstrated clinical improvement. However, one patient with atypical findings on histology did not show any clinical improvement, hence, underwent (68)Gallium-DOTANOC PET-ceCT scan for relocalization of the site of the tumor. The tumors causing TIO are small in size and usually located in obscure sites in the body. Hence, head to toe protocol should be followed for FDG PET-ceCT scans with the inclusion of upper limbs. Once the tumor is localized, regional magnetic resonance imaging can be performed for better characterization of soft tissue lesion. Imaging with FDG PET-ceCT plays an important role in detecting the site of the tumor and thereby facilitating timely management.

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy.

PubMed

Russmann, Vera; Brendel, Matthias; Mille, Erik; Helm-Vicidomini, Angela; Beck, Roswitha; Günther, Lisa; Lindner, Simon; Rominger, Axel; Keck, Michael; Salvamoser, Josephine D; Albert, Nathalie L; Bartenstein, Peter; Potschka, Heidrun

2017-01-01

Excessive activation of inflammatory signaling pathways seems to be a hallmark of epileptogenesis. Positron emission tomography (PET) allows in vivo detection of brain inflammation with spatial information and opportunities for longitudinal follow-up scanning protocols. Here, we assessed whether molecular imaging of the 18 kDa translocator protein (TSPO) can serve as a biomarker for the development of epilepsy. Therefore, brain uptake of [ 18 F]GE-180, a highly selective radioligand of TSPO, was investigated in a longitudinal PET study in a chronic rat model of temporal lobe epilepsy. Analyses revealed that the influence of the epileptogenic insult on [ 18 F]GE-180 brain uptake was most pronounced in the earlier phase of epileptogenesis. Differences were evident in various brain regions during earlier phases of epileptogenesis with [ 18 F]GE-180 standardized uptake value enhanced by 2.1 to 2.7fold. In contrast, brain regions exhibiting differences seemed to be more restricted with less pronounced increases of tracer uptake by 1.8-2.5fold four weeks following status epilepticus and by 1.5-1.8fold in the chronic phase. Based on correlation analysis, we were able to identify regions with a predictive value showing a correlation with seizure development. These regions include the amygdala as well as a cluster of brain areas. This cluster comprises parts of different brain regions, e.g. the hippocampus, parietal cortex, thalamus, and somatosensory cortex. In conclusion, the data provide evidence that [ 18 F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

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

PubMed

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

2017-06-01

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

Impact of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Before and After Definitive Radiation Therapy in Patients With Apparently Solitary Plasmacytoma

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

Kim, Paul J.; Hicks, Rodney J.; Wirth, Andrew

2009-07-01

Purpose: To evaluate the impact of {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Methods and Materials: Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Results: Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%).more » Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). Conclusions: FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.« less

Proton irradiation of [18O]O2: production of [18F]F2 and [18F]F2 + [18F] OF2.

PubMed

Bishop, A; Satyamurthy, N; Bida, G; Hendry, G; Phelps, M; Barrio, J R

1996-04-01

The production of 18F electrophilic reagents via the 18O(p,n)18F reaction has been investigated in small-volume target bodies made of aluminum, copper, gold-plated copper and nickel, having straight or conical bore shapes. Three irradiation protocols-single-step, two-step and modified two-step-were used for the recovery of the 18F activity. The single-step irradiation protocol was tested in all the target bodies. Based on the single-step performance, aluminum targets were utilized extensively in the investigation of the two-step and modified two-step irradiation protocols. With an 11-MeV cyclotron and using the two-step irradiation protocol, > 1Ci [18F]F2 was recovered reproducibly from an aluminum target body. Probable radical mechanisms for the formation of OF2 and FONO2 (fluorine nitrate) in the single-step and modified two-step targets are proposed based on the amount of ozone generated and the nitrogen impurity present in the target gases, respectively.

Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: a systematic review and a meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Prior, John O; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols

DOEpatents

Shiue, Chyng-Yann; Wolf, Alfred P.; Bai, Lan-Qin; Teng, Ren-Tui

1989-01-01

There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.

Optimization of the reference region method for dual pharmacokinetic modeling using Gd-DTPA/MRI and (18) F-FDG/PET.

PubMed

Poulin, Éric; Lebel, Réjean; Croteau, Étienne; Blanchette, Marie; Tremblay, Luc; Lecomte, Roger; Bentourkia, M'hamed; Lepage, Martin

2015-02-01

The combination of MRI and positron emission tomography (PET) offers new possibilities for the development of novel methodologies. In pharmacokinetic image analysis, the blood concentration of the imaging compound as a function of time, [i.e., the arterial input function (AIF)] is required for MRI and PET. In this study, we tested whether an AIF extracted from a reference region (RR) in MRI can be used as a surrogate for the manually sampled (18) F-FDG AIF for pharmacokinetic modeling. An MRI contrast agent, gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and a radiotracer, (18) F-fluorodeoxyglucose ((18) F-FDG), were simultaneously injected in a F98 glioblastoma rat model. A correction to the RR AIF for Gd-DTPA is proposed to adequately represent the manually sampled AIF. A previously published conversion method was applied to convert this AIF into a (18) F-FDG AIF. The tumor metabolic rate of glucose (TMRGlc) calculated with the manually sampled (18) F-FDG AIF, the (18) F-FDG AIF converted from the RR AIF and the (18) F-FDG AIF converted from the corrected RR AIF were found not statistically different (P>0.05). An AIF derived from an RR in MRI can be accurately converted into a (18) F-FDG AIF and used in PET pharmacokinetic modeling. © 2014 Wiley Periodicals, Inc.

Concordance between (99m)Tc-ECD SPECT and 18F-FDG PET interpretations in patients with cognitive disorders diagnosed according to NIA-AA criteria.

PubMed

Ito, Kimiteru; Shimano, Yasumasa; Imabayashi, Etsuko; Nakata, Yasuhiro; Omachi, Yoshie; Sato, Noriko; Arima, Kunimasa; Matsuda, Hiroshi

2014-10-01

The purpose of this study was to clarify the concordance of diagnostic abilities and interobserver agreement between 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and brain perfusion single photon-emission computed tomography (SPECT) in patients with Alzheimer's disease (AD) who were diagnosed according to the research criteria of the National Institute of Aging-Alzheimer's Association Workshop. Fifty-five patients with "AD and mild cognitive impairment (MCI)" (n = 40) and "non-AD" (n = 15) were evaluated with 18F-FDG PET and (99m)Tc-ethyl cysteinate dimer (ECD) SPECT during an 8-week period. Three radiologists independently graded the regional uptake in the frontal, temporal, parietal, and occipital lobes as well as the precuneus/posterior cingulate cortex in both images. Kappa values were used to determine the interobserver reliability regarding regional uptake. The regions with better interobserver reliability between 18F-FDG PET and (99m)Tc-ECD SPECT were the frontal, parietal, and temporal lobes. The (99m)Tc-ECD SPECT agreement in the occipital lobes was not significant. The frontal, temporal, and parietal lobes showed good correlations between 18F-FDG PET and (99m)Tc-ECD SPECT in the degree of uptake, but the occipital lobe and precuneus/posterior cingulate cortex did not show good correlations. The diagnostic accuracy rates of "AD and MCI" ranged from 60% to 70% in both of the techniques. The degree of uptake on 18F-FDG PET and (99m)Tc-ECD SPECT showed significant correlations in the frontal, temporal, and parietal lobes. The diagnostic abilities of 18F-FDG PET and (99m)Tc-ECD SPECT for "AD and MCI," when diagnosed according to the National Institute of Aging-Alzheimer's Association Workshop criteria, were nearly identical. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed

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

2012-01-01

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

Convenient and Efficient Method for Quality Control Analysis of 18F-Fluorocholine: For a Small Scale GMP-based Radiopharmaceuticals Laboratory Set-up.

PubMed

Hassan, Hishar; Abu Bakar, Suharzelim; Halim, Khairul Najah Che A; Idris, Jaleezah; Nordin, Abdul Jalil

2016-01-01

Prostate cancer continues to be the most prevalent cancer in men in Malaysia. As time progresses, the prospect of PET imaging modality in diagnosis of prostate cancer is promising, with on-going improvement on novel tracers. Among all tracers, 18F-Fluorocholine is reported to be a reputable tracer and reliable diagnostic technique for prostate imaging. Nonetheless, only 18F-Fluorodeoxyglucose (18F-FDG) is available and used in most oncology cases in Malaysia. With a small scale GMP-based radiopharmaceuticals laboratory set-up, initial efforts have been taken to put Malaysia on 18F-Fluorocholine map. This article presents a convenient, efficient and reliable method for quality control analysis of 18F-Fluorocholine. Besides, the aim of this research work is to assist local GMP radiopharmaceuticals laboratories and local authority in Malaysia for quality control analysis of 18F-Fluorocholine guideline. In this study, prior to synthesis, quality control analysis method for 18F-Fluorocholine was developed and validated, by adapting the equipment set-up used in 18F-Fluorodeoxyglucose (18FFDG) routine production. Quality control on the 18F-Fluorocholine was performed by means of pH, radionuclidic identity, radio-high performance liquid chromatography equipped with ultraviolet, radio- thin layer chromatography, gas chromatography and filter integrity test. Post-synthesis; the pH of 18F-Fluorocholine was 6.42 ± 0.04, with half-life of 109.5 minutes (n = 12). The radiochemical purity was consistently higher than 99%, both in radio-high performance liquid chromatography equipped with ultraviolet (r-HPLC; SCX column, 0.25 M NaH2PO4: acetonitrile) and radio-thin layer chromatography method (r-TLC). The calculated relative retention time (RRT) in r-HPLC was 1.02, whereas the retention factor (Rf) in r-TLC was 0.64. Potential impurities from 18F-Fluorocholine synthesis such as ethanol, acetonitrile, dimethylethanolamine and dibromomethane were determined in gas chromatography

Whole-body biodistribution and radiation dosimetry of 18F-FP-(+)-DTBZ (18F-AV-133): a novel vesicular monoamine transporter 2 imaging agent.

PubMed

Lin, Kun-Ju; Weng, Yi-Hsin; Wey, Shiaw-Pyng; Hsiao, Ing-Tsung; Lu, Chin-Song; Skovronsky, Daniel; Chang, Hsiu-Ping; Kung, Mei-Ping; Yen, Tzu-Chen

2010-09-01

Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the endocrine cells and brain. We investigated the biodistribution and radiation dosimetry of (2R,3R,11bR)-9-(3-(18)F-fluoropropoxy)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ((18)F-FP-(+)-dihydrotetrabenazine [DTBZ] or (18)F-AV-133), a potential VMAT2 imaging agent showing encouraging results in humans, to facilitate its future clinical use. Nine healthy human subjects (mean age +/- SD, 58.6 +/- 4.2 y) were enrolled for the whole-body PET scan. Serial images were acquired for 3 h immediately after a bolus injection of 390.7 +/- 22.9 MBq of (18)F-AV-133 per individual. The source organs were delineated on PET/CT images. The OLINDA/EXM application was used to determine the equivalent dose for individual organs. The radiotracer did not show any noticeable adverse effects for the 9 subjects examined. The radioactivity uptake in the brain was the highest at 7.5% +/- 0.6% injected dose at 10 min after injection. High absorbed doses were found in the pancreas, liver, and upper large intestine wall. The highest-dosed organ, which received 153.3 +/- 23.8 microGy/MBq, was the pancreas. The effective dose equivalent and effective dose for (18)F-AV-133 were 36.5 +/- 2.8 and 27.8 +/- 2.5 microSv/MBq, respectively. These values are comparable to those reported for any other (18)F-labeled radiopharmaceutical. (18)F-AV-133 is safe, with appropriate biodistribution and radiation dosimetry for imaging VMAT2 sites in humans.

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

PubMed

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

2010-03-01

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

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

PubMed

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

2016-04-01

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

Prognostic Value of SUVmax Measured by Pretreatment Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ewing Sarcoma

PubMed Central

Hwang, Jae Pil; Lim, Ilhan; Kong, Chang-Bae; Jeon, Dae Geun; Byun, Byung Hyun; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo

2016-01-01

Aim The aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma. Methods We retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox’s proportional hazards regression model. Results The median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2–18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63–508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34–54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21–43.95; HR, 7.3) were associated with worse overall survival. Conclusions SUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma. PMID:27100297

Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT.

PubMed

Thanseer, N T K; Bhadada, Sanjay Kumar; Sood, Ashwani; Parihar, Ashwin Singh; Dahiya, Divya; Singh, Priyanka; Basher, Rajender Kumar; Das, Ashim; Mittal, Bhagwant R

2018-04-01

18 F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of 18 F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented.

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

PubMed

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

1998-03-01

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

Evaluation in Monkey of Two Candidate PET Radioligands, [11C]RX-1 and [18F]RX-2, for Imaging Brain 5-HT4 Receptors

PubMed Central

LOHITH, TALAKAD G.; XU, RONG; TSUJIKAWA, TETSUYA; MORSE, CHERYL L.; ANDERSON, KACEY B.; GLADDING, ROBERT L.; ZOGHBI, SAMI S.; FUJITA, MASAHIRO; INNIS, ROBERT B.; PIKE, VICTOR W.

2014-01-01

The serotonin subtype-4 (5-HT4) receptor, which is known to be involved physiologically in learning and memory, and pathologically in Alzheimer’s disease, anxiety and other neuropsychiatric disorders – has few radioligands readily available for imaging in vivo. We have previously reported two novel 5-HT4 receptor radioligands, namely [methoxy-11C](1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate; [11C]RX-1) and the [18F]3-fluoromethoxy analog ([18F]RX-2), and in this study we evaluated them by PET in rhesus monkey. Brain scans were performed at baseline, receptor preblock or displacement conditions using SB 207710, a 5-HT4 receptor antagonist, on the same day for [11C]RX-1 and on different days for [18F]RX-2. Specific-to-nondisplaceable ratio (BPND) was measured with the simplified reference tissue model from all baseline scans. To determine specific binding, total distribution volume (VT) was also measured in some monkeys by radiometabolite-corrected arterial input function after ex vivo inhibition of esterases from baseline and blocked scans. Both radioligands showed moderate to high peak brain uptake of radioactivity (2–6 SUV). Regional BPND values were in the rank order of known 5-HT4 receptor distribution with a trend for higher BPND values from [18F]RX-2. One-tissue compartmental model provided good fits with well identified VT values for both radioligands. In the highest 5-HT4 receptor density region, striatum, 50–60% of total binding was specific. The VT in receptor-poor cerebellum reached stable values by about 60 min for both radioligands indicating little influence of radiometabolites on brain signal. In conclusion, both [11C]RX-1 and [18F]RX-2 showed positive attributes for PET imaging of brain 5-HT4 receptors, validating the radioligand design strategy. PMID:25088028

Diagnostic importance of contrast enhanced 18F-fluorodeoxyglucose positron emission computed tomography in patients with tumor induced osteomalacia: Our experience

PubMed Central

Jain, Avani S.; Shelley, Simon; Muthukrishnan, Indirani; Kalal, Shilpa; Amalachandran, Jaykanth; Chandran, Sureshkumar

2016-01-01

Aims and Objectives: To assess the diagnostic utility of contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-ceCT) in localization of tumors in patients with clinical diagnosis of tumor-induced osteomalacia (TIO), in correlation with histopathological results. Materials and Methods: Eight patients (five male and three female) aged 24–60 (mean 42) years with a clinical diagnosis of TIO were included in this prospective study. They underwent whole body (head to toe) FDG PET-ceCT following a standard protocol on Philips GEMINI TF PET-CT scanner. The FDG PET-ceCT results were correlated with postoperative histology findings and clinical follow-up. Results: All the patients had an abnormal PET-ceCT study. The sensitivity of PET-ceCT was 87.5%, and positive predictive value was 100%. The tumor was located in the craniofacial region in 6/8 patients and in bone in 2/8 patients. Hemangiopericytoma was the most common reported histology. All patients underwent surgery, following which they demonstrated clinical improvement. However, one patient with atypical findings on histology did not show any clinical improvement, hence, underwent 68Gallium-DOTANOC PET-ceCT scan for relocalization of the site of the tumor. Conclusion: The tumors causing TIO are small in size and usually located in obscure sites in the body. Hence, head to toe protocol should be followed for FDG PET-ceCT scans with the inclusion of upper limbs. Once the tumor is localized, regional magnetic resonance imaging can be performed for better characterization of soft tissue lesion. Imaging with FDG PET-ceCT plays an important role in detecting the site of the tumor and thereby facilitating timely management. PMID:26917888

Data-driven identification of intensity normalization region based on longitudinal coherency of 18F-FDG metabolism in the healthy brain.

PubMed

Zhang, Huiwei; Wu, Ping; Ziegler, Sibylle I; Guan, Yihui; Wang, Yuetao; Ge, Jingjie; Schwaiger, Markus; Huang, Sung-Cheng; Zuo, Chuantao; Förster, Stefan; Shi, Kuangyu

2017-02-01

In brain 18 F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. 127 female and 128 male healthy subjects (age: 20 to 79) with brain 18 F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18 F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R 2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both

Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.

PubMed

Nieto, Elena; Delgado, Mercedes; Sobrado, Mónica; de Ceballos, María L; Alajarín, Ramón; García-García, Luis; Kelly, James; Lizasoain, Ignacio; Pozo, Miguel A; Álvarez-Builla, Julio

2015-08-28

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A rare adult renal neuroblastoma better imaged by 18F-FDG than by 68Ga-dotanoc in the PET/CT scan.

PubMed

Jain, Tarun Kumar; Singh, Sharwan Kumar; Sood, Ashwani; Ashwathanarayama, Abhiram Gj; Basher, Rajender Kumar; Shukla, Jaya; Mittal, Bhagwant Rai

2017-01-01

Primary renal neuroblastoma is an uncommon tumor in children and extremely rare in adults. We present a case of a middle aged female having a large retroperitoneal mass involving the right kidney with features of neuroblastoma on pre-operative histopathology. Whole-body fluorine-18-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG PET/CT) and 68 Ga-dotanoc PET/CT scans performed for staging and therapeutic potential revealed a tracer avid mass replacing the right kidney and also pelvic lymph nodes. The 18 F-FDG PET/CT scan showed better both the primary lesion and the metastases in the pelvic lymph nodes than the 68 Ga-dotanoc scan supporting diagnosis and treatment planning.

[(18)F]FDG PET Neuroimaging Predicts Pentylenetetrazole (PTZ) Kindling Outcome in Rats.

PubMed

Bascuñana, Pablo; Javela, Julián; Delgado, Mercedes; Fernández de la Rosa, Rubén; Shiha, Ahmed Anis; García-García, Luis; Pozo, Miguel Ángel

2016-10-01

Epileptogenesis, i.e., development of epilepsy, involves a number of processes that alter the brain function in the way that triggers spontaneous seizures. Kindling is one of the most used animal models of temporal lobe epilepsy (TLE) and epileptogenesis, although chemical kindling suffers from high inter-assay success unpredictability. This study was aimed to analyze the eventual regional brain metabolic changes during epileptogenesis in the pentylenetetrazole (PTZ) kindling model in order to obtain a predictive kindling outcome parameter. In vivo longitudinal positron emission tomography (PET) scans with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) along the PTZ kindling protocol (35 mg/kg intraperitoneally (i.p.), 18 sessions) in adult male rats were performed in order to evaluate the regional brain metabolism. The half of the PTZ-injected rats reached the kindled state. In addition, a significant decrease of [(18)F]FDG uptake at the end of the protocol in most of the brain structures of kindled animals was found, reflecting the characteristic epilepsy-associated hypometabolism. However, PTZ-injected animals but not reaching the kindled state did not show this widespread brain hypometabolism. Retrospective analysis of the data revealed that hippocampal [(18)F]FDG uptake normalized to pons turned out to be a predictive index of the kindling outcome. Thus, a 19.06 % reduction (p = 0.008) of the above parameter was found in positively kindled rats compared to non-kindled ones just after the fifth PTZ session. Non-invasive PET neuroimaging was a useful tool for discerning epileptogenesis progression in this animal model. Particularly, the [(18)F]FDG uptake of the hippocampus proved to be an early predictive parameter to differentiate resistant and non-resistant animals to the PTZ kindling.

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Measurements of occupational exposure for a technologist performing 18F FDG PET scans.

PubMed

Biran, Talma; Weininger, Jolie; Malchi, Shalom; Marciano, Rami; Chisin, Roland

2004-11-01

Radiation doses to one PET technologist performing 100 18F FDG (18F fluorodeoxyglucose) imaging procedures were measured in a clinical setting using two types of thermoluminescent dosimeter (TLD) badges, one finger-ring TLD and one electronic pocket dosimeter (EPD). 18F FDG was handled either with unshielded or with viewing window tungsten shielded syringes. The resulting doses using unshielded syringes were 13.8 +/- 0.8 microSv/370 MBq and 14.3 +/- 0.4 microSv/370 MBq, measured with TLD 100 and with TLD 700H/600H, respectively. For the same series of measurements, the doses obtained using shielded syringes were 10.7 +/- 0.4 microSv/370 MBq and 7.2 +/- 2.1 microSv/370 MBq with TLD700H/600H and with EPD, respectively. The dose to the right hand from shielded syringes was 69.3 +/- 5.5 microSv/370 MBq. All these values are within the ICRP recommended dose limits. Extrapolated to 725 examinations per year, the resulting effective dose measured with TLD would be 10 mSv with unshielded and 7.5 mSv with shielded syringes, respectively (25% dose reduction). The doses measured by TLD were consistently higher than those measured by EPD, suggesting that EPD measurements might underestimate occupational doses.

18F-FDG uptake and its clinical relevance in primary gastric lymphoma.

PubMed

Yi, Jun Ho; Kim, Seok Jin; Choi, Joon Young; Ko, Young Hyeh; Kim, Byung-Tae; Kim, Won Seog

2010-06-01

We studied the clinical relevance of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in patients with primary gastric lymphoma underwent positron emission tomography (PET)/ computed tomography (CT) scan. Forty-two patients with primary gastric lymphoma were analysed: 32 diffuse large B-cell lymphomas (DLBCL) and 10 extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas). The PET/CT scans were compared with clinical and pathologic features, and the results of CT and endoscopy. Nine patients were up-staged based on the results of their PET/CT scan compared to CT (seven DLBCLs, two MALT lymphomas) while six patients were down-staged by the PET/CT scan. The standard uptake value (SUV) was used as an indicator of a lesion with a high metabolic rate. The high SUVmax group, defined as an SUVmax >or= median value, was significantly associated with an advanced Lugano stage (p < 0.001). Three patients with DLBCL, who showed an initially high SUVmax, died of disease progression. Among 24 patients for whom follow-up PET/CT scan with endoscopy was performed, 11 patients with ulcerative or mucosal lesions showed residual (18)F-FDG uptake. All of these gastric lesions were grossly and pathologically benign lesions without evidence of lymphoma cells. In conclusion, PET/CT scan can be used in staging patients with primary gastric lymphoma; however, the residual (18)F-FDG uptake observed during follow-up should be interpreted cautiously and should be combined with endoscopy and multiple biopsies of the stomach. (c) 2009 John Wiley & Sons, Ltd.

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

PubMed

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

2014-08-01

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

The effect of 18F-FDG-PET image reconstruction algorithms on the expression of characteristic metabolic brain network in Parkinson's disease.

PubMed

Tomše, Petra; Jensterle, Luka; Rep, Sebastijan; Grmek, Marko; Zaletel, Katja; Eidelberg, David; Dhawan, Vijay; Ma, Yilong; Trošt, Maja

2017-09-01

To evaluate the reproducibility of the expression of Parkinson's Disease Related Pattern (PDRP) across multiple sets of 18F-FDG-PET brain images reconstructed with different reconstruction algorithms. 18F-FDG-PET brain imaging was performed in two independent cohorts of Parkinson's disease (PD) patients and normal controls (NC). Slovenian cohort (20 PD patients, 20 NC) was scanned with Siemens Biograph mCT camera and reconstructed using FBP, FBP+TOF, OSEM, OSEM+TOF, OSEM+PSF and OSEM+PSF+TOF. American Cohort (20 PD patients, 7 NC) was scanned with GE Advance camera and reconstructed using 3DRP, FORE-FBP and FORE-Iterative. Expressions of two previously-validated PDRP patterns (PDRP-Slovenia and PDRP-USA) were calculated. We compared the ability of PDRP to discriminate PD patients from NC, differences and correlation between the corresponding subject scores and ROC analysis results across the different reconstruction algorithms. The expression of PDRP-Slovenia and PDRP-USA networks was significantly elevated in PD patients compared to NC (p<0.0001), regardless of reconstruction algorithms. PDRP expression strongly correlated between all studied algorithms and the reference algorithm (r⩾0.993, p<0.0001). Average differences in the PDRP expression among different algorithms varied within 0.73 and 0.08 of the reference value for PDRP-Slovenia and PDRP-USA, respectively. ROC analysis confirmed high similarity in sensitivity, specificity and AUC among all studied reconstruction algorithms. These results show that the expression of PDRP is reproducible across a variety of reconstruction algorithms of 18F-FDG-PET brain images. PDRP is capable of providing a robust metabolic biomarker of PD for multicenter 18F-FDG-PET images acquired in the context of differential diagnosis or clinical trials. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Amyloid and tau signatures of brain metabolic decline in preclinical Alzheimer's disease.

PubMed

Pascoal, Tharick A; Mathotaarachchi, Sulantha; Shin, Monica; Park, Ah Yeon; Mohades, Sara; Benedet, Andrea L; Kang, Min Su; Massarweh, Gassan; Soucy, Jean-Paul; Gauthier, Serge; Rosa-Neto, Pedro

2018-06-01

We aimed to determine the amyloid (Aβ) and tau biomarker levels associated with imminent Alzheimer's disease (AD) - related metabolic decline in cognitively normal individuals. A threshold analysis was performed in 120 cognitively normal elderly individuals by modelling 2-year declines in brain glucose metabolism measured with [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) as a function of [ 18 F]florbetapir Aβ positron emission tomography (PET) and cerebrospinal fluid phosphorylated tau biomarker thresholds. Additionally, using a novel voxel-wise analytical framework, we determined the sample sizes needed to test an estimated 25% drugeffect with 80% of power on changes in FDG uptake over 2 years at every brain voxel. The combination of [ 18 F]florbetapir standardized uptake value ratios and phosphorylated-tau levels more than one standard deviation higher than their respective thresholds for biomarker abnormality was the best predictor of metabolic decline in individuals with preclinical AD. We also found that a clinical trial using these thresholds would require as few as 100 individuals to test a 25% drug effect on AD-related metabolic decline over 2 years. These results highlight the new concept that combined Aβ and tau thresholds can predict imminent neurodegeneration as an alternative framework with a high statistical power for testing the effect of disease-modifying therapies on [ 18 F]FDG uptake decline over a typical 2-year clinical trial period in individuals with preclinical AD.

Role of 18F-FDG PET/CT in the Carcinoma of the Uterus: A Review of Literature

PubMed Central

Musto, Alessandra; Grassetto, Gaia; Marzola, Maria Cristina; Chondrogiannis, Sotirios; Maffione, Anna Margherita; Rampin, Lucia; Fuster, David; Giammarile, Francesco; Colletti, Patrick M.

2014-01-01

In the present review we reported the value of 18F-fluorodeoxyglucose (FDG) PET/CT in face of uterine cancer, in terms of sensitivity, specificity and accuracy. Moreover, we made a comparison with the other imaging techniques currently used to evacuate these tumors including contrast-enhanced CT, contrast enhanced-MRI and transvaginal ultrasonography. FDG PET/CT has been reported to be of particular value in detecting occult metastatic lesions, in prediction of response to treatment and as a pro-gnostic factor. PMID:25323881

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

PubMed

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

2015-03-01

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

Movement Correction Method for Human Brain PET Images: Application to Quantitative Analysis of Dynamic [18F]-FDDNP Scans

PubMed Central

Wardak, Mirwais; Wong, Koon-Pong; Shao, Weber; Dahlbom, Magnus; Kepe, Vladimir; Satyamurthy, Nagichettiar; Small, Gary W.; Barrio, Jorge R.; Huang, Sung-Cheng

2010-01-01

Head movement during a PET scan (especially, dynamic scan) can affect both the qualitative and quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic [18F]-FDDNP PET images of cognitively intact controls and patients with Alzheimer’s disease (AD). Methods Dynamic [18F]-FDDNP PET images, used for in vivo imaging of beta-amyloid plaques and neurofibrillary tangles, were obtained from 12 AD and 9 age-matched controls. For each study, a transmission scan was first acquired for attenuation correction. An accurate retrospective MC method that corrected for transmission-emission misalignment as well as emission-emission misalignment was applied to all studies. No restriction was assumed for zero movement between the transmission scan and first emission scan. Logan analysis with cerebellum as the reference region was used to estimate various regional distribution volume ratio (DVR) values in the brain before and after MC. Discriminant analysis was used to build a predictive model for group membership, using data with and without MC. Results MC improved the image quality and quantitative values in [18F]-FDDNP PET images. In this subject population, medial temporal (MTL) did not show a significant difference between controls and AD before MC. However, after MC, significant differences in DVR values were seen in frontal, parietal, posterior cingulate (PCG), MTL, lateral temporal (LTL), and global between the two groups (P < 0.05). In controls and AD, the variability of regional DVR values (as measured by the coefficient of variation) decreased on average by >18% after MC. Mean DVR separation between controls and ADs was higher in frontal, MTL, LTL and global after MC. Group classification by discriminant analysis based on [18F]-FDDNP DVR values was markedly improved after MC. Conclusion

18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis.

PubMed

Grayson, Peter C; Alehashemi, Sara; Bagheri, Armin A; Civelek, Ali Cahid; Cupps, Thomas R; Kaplan, Mariana J; Malayeri, Ashkan A; Merkel, Peter A; Novakovich, Elaine; Bluemke, David A; Ahlman, Mark A

2018-03-01

To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months. FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse. © 2017

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

PubMed

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

2018-05-22

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

Automated cGMP-compliant radiosynthesis of [18 F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5.

PubMed

Park, Jun Young; Son, Jeongmin; Yun, Mijin; Ametamey, Simon M; Chun, Joong-Hyun

2018-01-01

(E)-3-(Pyridin-2-yl ethynyl)cyclohex-2-enone O-(3-(2-[ 18 F]-fluoroethoxy)propyl) oxime ([ 18 F]-(E)-PSS232, [ 18 F]2a) is a recently developed radiotracer that can be used to visualize metabotropic glutamate receptor subtype 5 (mGlu 5 ) in vivo. The mGlu 5 has become an attractive therapeutic and diagnostic target owing to its role in many neuropsychiatric disorders. Several carbon-11-labeled and fluorine-18-labeled radiotracers have been developed to measure mGlu 5 receptor occupancy in the human brain. The radiotracer [ 18 F]2a, which is used as an analogue for [ 11 C]ABP688 ([ 11 C]1) and has a longer physical half-life, is a selective radiotracer that exhibits high binding affinity for mGlu 5 . Herein, we report the fully automated radiosynthesis of [ 18 F]2a using a commercial GE TRACERlab™ FX- FN synthesizer for routine production and distribution to nearby satellite clinics. Nucleophilic substitution of the corresponding mesylate precursor with cyclotron-produced [ 18 F]fluoride ion at 100°C in dimethyl sulfoxide (DMSO), followed by high-performance liquid chromatography (HPLC) purification and formulation, readily provided [ 18 F]2a with a radiochemical yield of 40 ± 2% (decay corrected, n = 5) at the end of synthesis. Radiochemical purity for the [ 18 F]-(E)-conformer was greater than 95%. Molar activity was determined to be 63.6 ± 9.6 GBq/μmol (n = 5), and the overall synthesis time was 70 minutes. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed

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

2016-01-01

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

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

PubMed Central

Manning, Kathryn Y.; Rajakumar, Nagalingam; Gómez, Francisco A.; Soddu, Andrea; Borrie, Michael J.

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1–42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD. PMID:28582450

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease.

PubMed

Kazemifar, Samaneh; Manning, Kathryn Y; Rajakumar, Nagalingam; Gómez, Francisco A; Soddu, Andrea; Borrie, Michael J; Menon, Ravi S; Bartha, Robert

2017-01-01

Previous studies have demonstrated altered brain activity in Alzheimer's disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from 18F FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid β1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD.

Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.

PubMed

Tago, Tetsuro; Furumoto, Shozo; Okamura, Nobuyuki; Harada, Ryuichi; Adachi, Hajime; Ishikawa, Yoichi; Yanai, Kazuhiko; Iwata, Ren; Kudo, Yukitsuka

2016-04-01

Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [(18)F]THK-5105 enantiomers. Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[(18)F]THK-5105. (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

Value of 18fluorodeoxyglucose-positron-emission tomography in amyotrophic lateral sclerosis: a prospective study.

PubMed

Van Laere, Koen; Vanhee, Annelies; Verschueren, Jolien; De Coster, Liesbeth; Driesen, An; Dupont, Patrick; Robberecht, Wim; Van Damme, Philip

2014-05-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting the motor system, with extramotor involvement to a variable extent. Biomarkers for early differential diagnosis and prognosis are needed. An autosomal dominant hexanucleotide (GGGGCC) expansion in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent genetic cause of ALS, but its metabolic pattern has not been studied systematically. To evaluate the use of 18fluorodeoxyglucose-positron-emission tomography as a marker of ALS pathology and investigate whether a specific metabolic signature is present in patients with C9orf72 mutations. In total, 81 patients with a suspected diagnosis of ALS at University Hospital Leuven were prospectively investigated. All underwent detailed neurological examination and electrodiagnostic and genetic testing for the major known genetic causes of ALS (C9orf72, SOD1, TARDBP, and FUS). A diagnosis of ALS was made in 70 of 81 patients. Of these, 11 were C9orf72 positive and 59 were C9orf72 negative. In 7 patients, the diagnosis of primary lateral sclerosis was made; 4 patients had progressive muscular atrophy. A screened healthy control population was used for comparison. Positron-emission tomographic data were spatially normalized and analyzed using a predefined volume of interest and a voxel-based analysis (SPM8). Discriminant analysis was done both volume of interest based and voxel based using a support vector machine approach. Compared with control participants, 18fluorodeoxyglucose-positron-emission tomography showed perirolandic and variable prefrontal hypometabolism in most patients. Patients with primary lateral sclerosis showed a similar pattern. Patients with C9orf72-positive ALS had discrete relative hypometabolism in the thalamus and posterior cingulate compared with those with C9orf72-negative ALS. A posteriori-corrected discriminant analysis was able to correctly classify 95% of ALS cases and

Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain.

PubMed

Feeney, Claire; Scott, Gregory; Raffel, Joel; Roberts, S; Coello, Christopher; Jolly, Amy; Searle, Graham; Goldstone, A P; Brooks, David J; Nicholas, Richard S; Trigg, William; Gunn, Roger N; Sharp, David J

2016-11-01

PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [ 11 C]PK-11195 limits accurate quantification. [ 18 F]GE-180, a novel TSPO ligand, displays superior binding to [ 11 C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [ 18 F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [ 18 F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T ) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1 ) was 0.01 mL cm -3  min -1 indicating low extraction across the blood-brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm -3 in the striatum to 0.38 mL cm -3 in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [ 18 F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of

Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching off Approaches Increasing Specificity for Detection of Recurrence

PubMed Central

Okuyucu, Kursat; Hancerliogulları, Oguz; Alagoz, Engin; San, Huseyin; Arslan, Nuri

2017-01-01

Abstract Background Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (l8F-FDG) positron emission tomography/computed tomography (PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of 18F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC. Patients and methods We examined the SUVmax value of lesions on control or restaging 18F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax values were confirmed by colonoscopy or histopathology. We compared PET/CT results with conventional imaging modalities (CT, MRI) and tumor markers (carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Results Mean SUVmax was 6.9 ± 5.6 in benign group, 12.7 ± 6.1 in malignant group. Mean TLG values of malignant group and benign group were 401 and 148, respectively. 18F-FDG-PET/CT was truely positive in 48% of patients with normal Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9 or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18F-FDG-PET/CT was truely negative in 35% of these cases. We found the most important and striking statistical difference of TLG value between the groups with benign and recurrent disease. Conclusions Although SUVmax is a strong metabolic parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p = 0.001); both are increasing the specificity of 18F-FDG-PET/CT. PMID:29333115

Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching off Approaches Increasing Specificity for Detection of Recurrence.

PubMed

Ince, Semra; Okuyucu, Kursat; Hancerliogulları, Oguz; Alagoz, Engin; San, Huseyin; Arslan, Nuri

2017-12-01

Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose ( l8 F-FDG) positron emission tomography/computed tomography (PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of 18 F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC. We examined the SUVmax value of lesions on control or restaging 18 F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax values were confirmed by colonoscopy or histopathology. We compared PET/CT results with conventional imaging modalities (CT, MRI) and tumor markers (carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Mean SUVmax was 6.9 ± 5.6 in benign group, 12.7 ± 6.1 in malignant group. Mean TLG values of malignant group and benign group were 401 and 148, respectively. 18 F-FDG-PET/CT was truely positive in 48% of patients with normal Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9 or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18 F-FDG-PET/CT was truely negative in 35% of these cases. We found the most important and striking statistical difference of TLG value between the groups with benign and recurrent disease. Although SUVmax is a strong metabolic parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p = 0.001); both are increasing the specificity of 18 F-FDG-PET/CT.

A comparative study of quantitative assessment with fluorine-18-fluorodeoxyglucose positron-emission tomography and endoscopic ultrasound in oesophageal cancer.

PubMed

Borakati, Aditya; Razack, Abdul; Cawthorne, Chris; Roy, Rajarshi; Usmani, Sharjeel; Ahmed, Najeeb

2018-07-01

This study aims to assess the correlation between PET/CT and endoscopic ultrasound (EUS) parameters in patients with oesophageal cancer. All patients who had complete PET/CT and EUS staging performed for oesophageal cancer at our centre between 2010 and 2016 were included. Images were retrieved and analysed for a range of parameters including tumour length, volume and position relative to the aortic arch. Seventy patients were included in the main analysis. A strong correlation was found between EUS and PET/CT in the tumour length, the volume and the position of the tumour relative to the aortic arch. Regression modelling showed a reasonable predictive value for PET/CT in calculating EUS parameters, with r higher than 0.585 in some cases. Given the strong correlation between EUS and PET parameters, fluorine-18 fluorodeoxyglucose (F-FDG) PET can provide accurate information on the length and the volume of tumour in patients who either cannot tolerate EUS or have impassable strictures.

Functional brain mapping of actual car-driving using [18F]FDG-PET.

PubMed

Jeong, Myeonggi; Tashiro, Manabu; Singh, Laxsmi N; Yamaguchi, Keiichiro; Horikawa, Etsuo; Miyake, Masayasu; Watanuki, Shouichi; Iwata, Ren; Fukuda, Hiroshi; Takahashi, Yasuo; Itoh, Masatoshi

2006-11-01

This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

Comparison between endoscopic macroscopic classification and F-18 FDG PET findings in gastric mucosa-associated lymphoid tissue lymphoma patients.

PubMed

Hirose, Yasumitsu; Kaida, Hayato; Ishibashi, Masatoshi; Uozumi, Jun; Arikawa, Shunji; Kurata, Seiji; Hayabuchi, Naofumi; Nakahara, Keita; Ohshima, Koichi

2012-02-01

The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis-like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis-like tumors and 40% for depressed-type tumors. F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

PubMed

Sun, Lijuan; Camps, Stefan G; Goh, Hui Jen; Govindharajulu, Priya; Schaefferkoetter, Joshua D; Townsend, David W; Verma, Sanjay K; Velan, S Sendhil; Sun, Lei; Sze, Siu Kwan; Lim, Su Chi; Boehm, Bernhard Otto; Henry, Christiani Jeyakumar; Leow, Melvin Khee-Shing

2018-01-01

Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). We compared capsinoids and cold exposure on BAT activation and whole-body EE. Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442. © 2018 American Society for Nutrition. All rights reserved.

Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

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

Ackermann, R.F.; Lear, J.L.

We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered ({sup 18}F)fluorodeoxyglucose (FDG) and ({sup 14}C)-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the {sup 14}C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the {sup 14}C label is lost frommore » the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.« less

Clinical impact of 18 F-FDG positron emission tomography/CT on adenoid cystic carcinoma of the head and neck.

PubMed

Jung, Ji-Hoon; Lee, Sang-Woo; Son, Seung Hyun; Kim, Choon-Young; Lee, Chang-Hee; Jeong, Ju Hye; Jeong, Shin Young; Ahn, Byeong-Cheol; Lee, Jaetae

2017-03-01

The purpose of this retrospective study was to assess the diagnostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and the prognostic value of metabolic PET parameters in patients with adenoid cystic carcinoma of the head and neck (ACCHN). Forty patients with newly diagnosed ACCHN were enrolled in this study. We investigated the diagnostic value of 18 F-FDG PET/CT for detecting and staging compared to conventional CT. Kaplan-Meier survival analysis for progression-free survival (PFS) was performed with clinicopathological factors and metabolic PET parameters. The 18 F-FDG PET/CT showed comparable sensitivity (92.3%) to conventional CT for lesion detection, and changed staging and management plan in 6 patients (15.0%). Lower PFS rates were associated with advanced T classification, advanced TNM classification, high maximum standardized uptake value (SUVmax; >5.1), and high total lesion glycolysis (>40.1) of the primary tumor. The 18 F-FDG PET/CT can provide additional information for initial staging, and metabolic PET parameters may serve as prognostic factors of ACCHN. © 2016 Wiley Periodicals, Inc. Head Neck 39: 447-455, 2017. © 2016 Wiley Periodicals, Inc.

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

PubMed Central

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

2014-01-01

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

Multidentate (18)F-polypegylated styrylpyridines as imaging agents for Aβ plaques in cerebral amyloid angiopathy (CAA).

PubMed

Zha, Zhihao; Choi, Seok Rye; Ploessl, Karl; Lieberman, Brian P; Qu, Wenchao; Hefti, Franz; Mintun, Mark; Skovronsky, Daniel; Kung, Hank F

2011-12-08

β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of (18)F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a-c, display high binding affinities and specificity to Aβ plaques (K(i) = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [(18)F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [(18)F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.

Advances in evaluation of primary brain tumors.

PubMed

Chen, Wei; Silverman, Daniel H S

2008-07-01

The evaluation of primary brain tumor is challenging. Neuroimaging plays a significant role. At diagnosis, imaging is needed to establish a differential diagnosis, provide prognostic information, as well as direct biopsy. After the initial treatment, imaging is needed to distinguish recurrent disease from treatment-related changes such as radiation necrosis. In low-grade gliomas, this also includes monitoring anaplastic transformation into high-grade tumors. Recently, targeted treatments have been an extremely active area of research. Evaluation in clinical trials of such targeted treatments demands advanced roles of imaging such as treatment planning, monitoring response, and predicting treatment outcomes. Current clinical gold standard magnetic resonance imaging provides superior structural detail but poor specificity in identifying viable tumors in treated brain with surgery/radiation/chemotherapy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is capable of identifying anaplastic transformation and has prognostic value. The sensitivity and specificity of FDG in evaluating recurrent tumor and treatment-induced changes can be significantly improved by coregistration with magnetic resonance imaging and potentially by delayed imaging 3 to 8 hours after injection. Amino acid PET tracers can be more sensitive than FDG in imaging some recurrent tumors, in particular recurrent low-grade tumors. They are also promising for differentiating between recurrent tumors and treatment-induced changes. Newer PET tracers to image important aspects of tumor biology have been actively studied. Tracers for imaging membrane transport such as (18)F-choline have shown promise in differential diagnosis. (18)F-labeled nucleotide analogs such as 3'-deoxy-3'-[(18)F]-fluorothymidine (FLT) and (18)F-FMAU have been developed to image proliferation. The use of FLT has demonstrated prognostic power in predicting treatment response in patients treated with an antiangiogenic

18F-FDG PET brain images as features for Alzheimer classification

NASA Astrophysics Data System (ADS)

Azmi, M. H.; Saripan, M. I.; Nordin, A. J.; Ahmad Saad, F. F.; Abdul Aziz, S. A.; Wan Adnan, W. A.

2017-08-01

2-Deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) Positron Emission Tomography (PET) imaging offers meaningful information for various types of diseases diagnosis. In Alzheimer's disease (AD), the hypometabolism of glucose which observed on the low intensity voxel in PET image may relate to the onset of the disease. The importance of early detection of AD is inevitable because the resultant brain damage is irreversible. Several statistical analysis and machine learning algorithm have been proposed to investigate the rate and the pattern of the hypometabolism. This study focus on the same aim with further investigation was performed on several hypometabolism pattern. Some pre-processing steps were implemented to standardize the data in order to minimize the effect of resolution and anatomical differences. The features used are the mean voxel intensity within the AD pattern mask, which derived from several z-score and FDR threshold values. The global mean voxel (GMV) and slice-based mean voxel (SbMV) intensity were observed and used as input to the neural network. Several neural network architectures were tested and compared to the nearest neighbour method. The highest accuracy equals to 0.9 and recorded at z-score ≤-1.3 with 1 node neural network architecture (sensitivity=0.81 and specificity=0.95) and at z-score ≤-0.7 with 10 nodes neural network (sensitivity=0.83 and specificity=0.94).

Pulmonary Actinomycosis Imitating Lung Cancer on (18)F-FDG PET/CT: A Case Report and Literature Review.

PubMed

Qiu, Lin; Lan, Lianjun; Feng, Yue; Huang, Zhanwen; Chen, Yue

2015-01-01

Here we report a case of 41-year-old man with a soft tissue density mass at right upper lung and palpable abscesses at right upper backside and right wrist. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography demonstrated a 7.8 × 5.0 cm mass with soft-tissue density in the upper lobe of the right lung with high metabolic activity. The infiltrative mass extended to adjacent chest wall soft tissue. Final diagnosis of pulmonary actinomycosis with multiple abscesses was made. The patient responded well to antibiotics treatment.

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

PubMed Central

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

2015-01-01

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

The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

PubMed

Thompson, Garth J; Riedl, Valentin; Grimmer, Timo; Drzezga, Alexander; Herman, Peter; Hyder, Fahmeed

2016-07-01

The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states.

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

PubMed

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

2009-04-01

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

Clinical utility of flumazenil-PET versus [18F]fluorodeoxyglucose-PET and MRI in refractory partial epilepsy. A prospective study in 100 patients.

PubMed

Ryvlin, P; Bouvard, S; Le Bars, D; De Lamérie, G; Grégoire, M C; Kahane, P; Froment, J C; Mauguière, F

1998-11-01

We assessed the clinical utility of [11C]flumazenil-PET (FMZ-PET) prospectively in 100 epileptic patients undergoing a pre-surgical evaluation, and defined the specific contribution of this neuro-imaging technique with respect to those of MRI and [18F]fluorodeoxyglucose-PET (FDG-PET). All patients benefited from a long term video-EEG monitoring, whereas an intracranial EEG investigation was performed in 40 cases. Most of our patients (73%) demonstrated a FMZ-PET abnormality; this hit rate was significantly higher in temporal lobe epilepsy (94%) than in other types of epilepsy (50%) (P < 0.001). Most FMZ-PET findings coexisted with a MRI abnormality (81%), including hippocampal atrophy (35%) and focal hypometabolism on FDG-PET (89%). The area of decreased FMZ binding was often smaller than that of glucose hypometabolism (48%) or larger than that of the MRI abnormality (28%). FMZ-PET did not prove superior to FDG-PET in assessing the extent of the ictal onset zone, as defined by intracranial EEG recordings. However, it provided useful data which were complementary to those of MRI and FDG-PET in three situations: (i) in temporal lobe epilepsy associated with MRI signs of hippocampal sclerosis, FMZ-PET abnormalities delineated the site of seizure onset precisely, whenever they were coextensive with FDG-PET abnormalities; (ii) in bi-temporal epilepsy, FMZ-PET helped to confirm the bilateral origin of seizures by showing a specific pattern of decreased FMZ binding in both temporal lobes in 33% of cases; (iii) in patients with a unilateral cryptogenic frontal lobe epilepsy, FMZ-PET provided further evidence of the side and site of seizure onset in 55% of cases. Thus, FMZ-PET deserves to be included in the pre-surgical evaluation of these specific categories of epileptic patients, representing approximately half of the population considered for epilepsy surgery.

18F-FDG uptake in the colon is modulated by metformin but not associated with core body temperature and energy expenditure.

PubMed

Bahler, Lonneke; Holleman, Frits; Chan, Man-Wai; Booij, Jan; Hoekstra, Joost B; Verberne, Hein J

2017-01-01

Physiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature. Therefore, we aimed to determine whether metformin modifies the metabolic activity of the colon by increasing glucose uptake. In this open label, non-randomized, prospective mechanistic study, we included eight lean and eight overweight males. We measured colonic 18F-FDG uptake on PET-CT, energy expenditure and core body temperature before and after the use of metformin. The maximal colonic 18F-FDG uptake was measured in 5 separate segments (caecum, colon ascendens,-transversum,-descendens and sigmoid). The maximal colonic 18F-FDG uptake increased significantly in all separate segments after the use of metformin. There was no significant difference in energy expenditure or core body temperature after the use of metformin. There was no correlation between maximal colonic 18F-FDG uptake and energy expenditure or core body temperature. Metformin significantly increases colonic 18F-FDG uptake, but this increased uptake is not associated with an increase in energy expenditure or core body temperature. Although the colon might be an important site of the glucose plasma lowering actions of metformin, this mechanism of action does not explain directly any associated weight loss.

Quantitative kinetic analysis of PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT in human brain.

PubMed

Shidahara, Miho; Watabe, Hiroshi; Tashiro, Manabu; Okamura, Nobuyuki; Furumoto, Shozo; Watanuki, Shoichi; Furukawa, Katsutoshi; Arakawa, Yuma; Funaki, Yoshihito; Iwata, Ren; Gonda, Kohsuke; Kudo, Yukitsuka; Arai, Hiroyuki; Ishiwata, Kiichi; Yanai, Kazuhiko

2015-09-01

The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain. Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients. For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different. This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers. Copyright © 2015 Elsevier Inc. All rights

Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates.

PubMed

Li, Songye; Cai, Zhengxin; Zheng, Ming-Qiang; Holden, Daniel; Naganawa, Mika; Lin, Shu-Fei; Ropchan, Jim; Labaree, David; Kapinos, Michael; Lara-Jaime, Teresa; Navarro, Antonio; Huang, Yiyun

2018-01-01

The κ-opioid receptor (KOR) has been implicated in depression, addictions, and other central nervous system disorders and, thus, is an important target for drug development. We previously developed several 11 C-labeled PET radiotracers for KOR imaging in humans. Here we report the synthesis and evaluation of 18 F-LY2459989 as the first 18 F-labeled KOR antagonist radiotracer in nonhuman primates and its comparison with 11 C-LY2459989. Methods: The novel radioligand 18 F-LY2459989 was synthesized by 18 F displacement of a nitro group or an iodonium ylide. PET scans in rhesus monkeys were obtained on a small-animal scanner to assess the pharmacokinetic and in vivo binding properties of the ligand. Metabolite-corrected arterial activity curves were measured and used as input functions in the analysis of brain time-activity curves and the calculation of binding parameters. Results: With the iodonium ylide precursor, 18 F-LY2459989 was prepared at high radiochemical yield (36% ± 7% [mean ± SD]), radiochemical purity (>99%), and mean molar activity (1,175 GBq/μmol; n = 6). In monkeys, 18 F-LY2459989 was metabolized at a moderate rate, with a parent fraction of approximately 35% at 30 min after injection. Fast and reversible kinetics were observed, with a regional peak uptake time of less than 20 min. Pretreatment with the selective KOR antagonist LY2456302 (0.1 mg/kg) decreased the activity level in regions with high levels of binding to that in the cerebellum, thus demonstrating the binding specificity and selectivity of 18 F-LY2459989 in vivo. Regional time-activity curves were well fitted by the multilinear analysis 1 kinetic model to derive reliable estimates of regional distribution volumes. With the cerebellum as the reference region, regional binding potentials were calculated and ranked as follows: cingulate cortex > insula > caudate/putamen > frontal cortex > temporal cortex > thalamus, consistent with the reported KOR distribution in the monkey brain

Dual acquisition of 18F-FMISO and 18F-FDOPA

NASA Astrophysics Data System (ADS)

Bell, Christopher; Rose, Stephen; Puttick, Simon; Pagnozzi, Alex; Poole, Christopher M.; Gal, Yaniv; Thomas, Paul; Fay, Michael; Jeffree, Rosalind L.; Dowson, Nicholas

2014-07-01

Metabolic imaging using positron emission tomography (PET) has found increasing clinical use for the management of infiltrating tumours such as glioma. However, the heterogeneous biological nature of tumours and intrinsic treatment resistance in some regions means that knowledge of multiple biological factors is needed for effective treatment planning. For example, the use of 18F-FDOPA to identify infiltrative tumour and 18F-FMISO for localizing hypoxic regions. Performing multiple PET acquisitions is impractical in many clinical settings, but previous studies suggest multiplexed PET imaging could be viable. The fidelity of the two signals is affected by the injection interval, scan timing and injected dose. The contribution of this work is to propose a framework to explicitly trade-off signal fidelity with logistical constraints when designing the imaging protocol. The particular case of estimating 18F-FMISO from a single frame prior to injection of 18F-FDOPA is considered. Theoretical experiments using simulations for typical biological scenarios in humans demonstrate that results comparable to a pair of single-tracer acquisitions can be obtained provided protocol timings are carefully selected. These results were validated using a pre-clinical data set that was synthetically multiplexed. The results indicate that the dual acquisition of 18F-FMISO and 18F-FDOPA could be feasible in the clinical setting. The proposed framework could also be used to design protocols for other tracers.

Diffuse thyroid uptake incidentally found on 18F-fluorodeoxyglucose positron emission tomography in subjects without cancer history.

PubMed

Lee, Ji Young; Choi, Joon Young; Choi, Yoon-Ho; Hyun, Seung Hyup; Moon, Seung Hwan; Jang, Su Jin; Choe, Yearn Seong; Lee, Kyung-Han; Kim, Byung-Tae

2013-01-01

We investigated the clinical significance of incidental diffuse thyroid uptake (DTU) on (18)F-FDG PET in subjects without a history of cancer. This study included 2062 studies from adults who underwent (18)F-FDG PET as a cancer screening program. Subjects were divided into the following two groups: with (group I) or without (group II) DTU. The presence of DTU and the thyroid visual grading score were compared with thyroid function tests, serum anti-microsomal antibody (AMA) levels, and the presence of diffuse parenchymal change (DPC) on ultrasonography (USG). DTU was found in 6.6% of the scans (137/2062). Serum thyroid stimulating hormone (TSH) and AMA levels were significantly higher in group I than in group II. Increased AMA level (55.1%) and DPC (48.7%) were more frequently found in group I (p < 0.001). The proportion of subjects with any abnormal results in serum free thyroxine, triiodothyronine, TSH, or AMA levels or DPC on USG was significantly higher in group I than in group II (71.5% vs. 10.6%, p < 0.001), and was significantly and gradually increased according to the visual grading score group (0 vs. 1-2 vs. 3-4 = 10.6% vs. 58.5% vs. 90.9%, p < 0.001). TSH and is AMA levels were significantly increased according to the visual grading score. The presence or degree of incidental DTU on (18)F-FDG PET is closely correlated with increased serum AMA and TSH levels, and the presence of DPC on USG. Therefore, the most plausible pathological cause of DTU may be cell damage by an autoimmune mechanism.

Effects of anesthetic protocol on normal canine brain uptake of 18F-FDG assessed by PET/CT.

PubMed

Lee, Min Su; Ko, Jeff; Lee, Ah Ra; Lee, In Hye; Jung, Mi Ae; Austin, Brenda; Chung, Hyunwoo; Nahm, Sangsoep; Eom, Kidong

2010-01-01

The purpose of this study was to assess the effects of four anesthetic protocols on normal canine brain uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using positron emission tomography/computed tomography (PET/CT). Five clinically normal beagle dogs were anesthetized with (1) propofol/isoflurane, (2) medetomidine/pentobarbital, (3) xylazine/ketamine, and (4) medetomidine/tiletamine-zolazepam in a randomized cross-over design. The standard uptake value (SUV) of FDG was obtained in the frontal, parietal, temporal and occipital lobes, cerebellum, brainstem and whole brain, and compared within and between anesthetic protocols using the Friedman test with significance set at P < 0.05. Significant differences in SUVs were observed in various part of the brain associated with each anesthetic protocol. The SUV for the frontal and occipital lobes was significantly higher than in the brainstem in all dogs. Dogs receiving medetomidine/tiletamine-zolazepam also had significantly higher whole brain SUVs than the propofol/isoflurane group. We concluded that each anesthetic protocol exerted a different regional brain glucose uptake pattern. As a result, when comparing brain glucose uptake using PET/CT, one should consider the effects of anesthetic protocols on different regions of the glucose uptake in the dog's brain.

Preoperative predictive model of cervical lymph node metastasis combining fluorine-18 fluorodeoxyglucose positron-emission tomography/computerized tomography findings and clinical factors in patients with oral or oropharyngeal squamous cell carcinoma.

PubMed

Mochizuki, Yumi; Omura, Ken; Nakamura, Shin; Harada, Hiroyuki; Shibuya, Hitoshi; Kurabayashi, Toru

2012-02-01

This study aimed to construct a preoperative predictive model of cervical lymph node metastasis using fluorine-18 fluorodeoxyglucose positron-emission tomography/computerized tomography ((18)F-FDG PET/CT) findings in patients with oral or oropharyngeal squamous cell carcinoma (SCC). Forty-nine such patients undergoing preoperative (18)F-FDG PET/CT and neck dissection or lymph node biopsy were enrolled. Retrospective comparisons with spatial correlation between PET/CT and the anatomical sites based on histopathological examinations of surgical specimens were performed. We calculated a logistic regression model, including the SUVmax-related variable. When using the optimal cutoff point criterion of probabilities calculated from the model that included either clinical factors and delayed-phase SUVmax ≥0.087 or clinical factors and maximum standardized uptake (SUV) increasing rate (SUV-IR) ≥ 0.100, it significantly increased the sensitivity, specificity, and accuracy (87.5%, 65.7%, and 75.2%, respectively). The use of predictive models that include clinical factors and delayed-phase SUVmax and SUV-IR improve preoperative nodal diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Fluorodeoxyglucose--positive internal mammary lymph node in breast cancer patients with silicone implants: is it always metastatic cancer?

PubMed

Soudack, Michalle; Yelin, Alon; Simansky, David; Ben-Nun, Alon

2013-07-01

Patients with breast cancer following mastectomy and silicone implant reconstruction may have enlarged internal mammary lymph nodes with pathological uptake on positron emission tomography with (18)F-fluorodeoxyglucose. This lymphadenopathy is usually considered as metastatic in nature, but has also been reported to be related to other conditions, including silicon migration. The purpose of this study was to determine the rate of metastatic disease in this unique group of patients. A retrospective comparative study of 12 female patients with breast cancer with silicone implants referred for biopsy due to isolated internal mammary lymph node fluorodeoxyglucose uptake on positron emission tomography. Five patients (41.6%) had histological findings related to silicone (n = 4) or non-specific inflammation (n = 1). The remaining 7 (58.3%) had histological evidence of cancer recurrence. There was no significant difference in the fluorodeoxyglucose-standardized uptake value between the two groups. Fluorodeoxyglucose-positive mammary lymph nodes in patients with breast cancer following silicone implant reconstruction may be due to metastatic deposits, non-specific inflammation or silicone migration. Clinical and imaging characteristics are insufficient in differentiating between these conditions. Biopsy is recommended prior to initiation of further treatment.

Preclinical Characterization of 18F-MK-6240, a Promising PET Tracer for In Vivo Quantification of Human Neurofibrillary Tangles.

PubMed

Hostetler, Eric D; Walji, Abbas M; Zeng, Zhizhen; Miller, Patricia; Bennacef, Idriss; Salinas, Cristian; Connolly, Brett; Gantert, Liza; Haley, Hyking; Holahan, Marie; Purcell, Mona; Riffel, Kerry; Lohith, Talakad G; Coleman, Paul; Soriano, Aileen; Ogawa, Aimie; Xu, Serena; Zhang, Xiaoping; Joshi, Elizabeth; Della Rocca, Joseph; Hesk, David; Schenk, David J; Evelhoch, Jeffrey L

2016-10-01

A PET tracer is desired to help guide the discovery and development of disease-modifying therapeutics for neurodegenerative diseases characterized by neurofibrillary tangles (NFTs), the predominant tau pathology in Alzheimer disease (AD). We describe the preclinical characterization of the NFT PET tracer 18 F-MK-6240. In vitro binding studies were conducted with 3 H-MK-6240 in tissue slices and homogenates from cognitively normal and AD human brain donors to evaluate tracer affinity and selectivity for NFTs. Immunohistochemistry for phosphorylated tau was performed on human brain slices for comparison with 3 H-MK-6240 binding patterns on adjacent brain slices. PET studies were performed with 18 F-MK-6240 in monkeys to evaluate tracer kinetics and distribution in the brain. 18 F-MK-6240 monkey PET studies were conducted after dosing with unlabeled MK-6240 to evaluate tracer binding selectivity in vivo. The 3 H-MK-6240 binding pattern was consistent with the distribution of phosphorylated tau in human AD brain slices. 3 H-MK-6240 bound with high affinity to human AD brain cortex homogenates containing abundant NFTs but bound poorly to amyloid plaque-rich, NFT-poor AD brain homogenates. 3 H-MK-6240 showed no displaceable binding in the subcortical regions of human AD brain slices and in the hippocampus/entorhinal cortex of non-AD human brain homogenates. In monkey PET studies, 18 F-MK-6240 displayed rapid and homogeneous distribution in the brain. The 18 F-MK-6240 volume of distribution stabilized rapidly, indicating favorable tracer kinetics. No displaceable binding was observed in self-block studies in rhesus monkeys, which do not natively express NFTs. Moderate defluorination was observed as skull uptake. 18 F-MK-6240 is a promising PET tracer for the in vivo quantification of NFTs in AD patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with (18)F-PBR111 PET.

PubMed

Colasanti, Alessandro; Guo, Qi; Muhlert, Nils; Giannetti, Paolo; Onega, Mayca; Newbould, Rexford D; Ciccarelli, Olga; Rison, Stuart; Thomas, Charlotte; Nicholas, Richard; Muraro, Paolo A; Malik, Omar; Owen, David R; Piccini, Paola; Gunn, Roger N; Rabiner, Eugenii A; Matthews, Paul M

2014-07-01

PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune

Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine.

PubMed

Fischer, Steffen; Wiese, Christian; Maestrup, Eva Grosse; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Schepmann, Dirk; Steinbach, Jörg; Wünsch, Bernhard; Brust, Peter

2011-03-01

Neuroimaging of σ(1) receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable (18)F-labelled PET radioligands for that purpose. The selective σ(1) receptor ligand [(18)F]fluspidine (1'-benzyl-3-(2-[(18)F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic (18)F(-) substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [(18)F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [(18)F]fluspidine after treatment with 1 mg/kg i.p. of the σ receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS(n) and radio-HPLC analysis. [(18)F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of ≥ 99.6% and a specific activity of 150-350 GBq/μmol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to σ(1) receptors (K (i) = 0.59 nM). In mice, [(18)F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [(18)F]fluspidine and the expression of σ(1) receptors was shown. The radiotracer uptake in the brain as well as in peripheral σ(1) receptor expressing organs was significantly inhibited by haloperidol but not by tamoxifen. Incubation with rat liver microsomes led to a fast

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

PubMed

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

2016-08-01

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

18F-fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma.

PubMed

Kim, Beom Kyung; Kang, Won Jun; Kim, Ja Kyung; Seong, Jinsil; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Lee, Do Youn; Lee, Kwang Hoon; Lee, Jong Doo; Han, Kwang-Hyub

2011-10-15

Metabolic activity assessed by (18)F-fluorodeoxyglocuse-positron emission tomography ((18)F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). Over a 3-year period (2005-2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received (18)F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. The median maximal tumor SUV was 6.1 (range, 2.4-∼19.2). Patients with low maximal tumor SUVs (<6.1) had a higher disease control rate than those with high maximal tumor SUVs (≥6.1) (86.8% vs 68.5%, respectively, P = .023). Both median progression-free survival (PFS; 8.4 vs 5.2 months; P = .003) and overall survival (OS; 17.9 vs 11.3 months; P = .013) were significantly longer in the low maximal tumor SUV group than in the high maximal tumor SUV group, respectively. In multivariate analysis, low maximal tumor SUV and objective responses to CCRT remained significant for PFS and OS. The high maximal tumor SUV group was more likely to have extrahepatic metastasis within 6 months than the low maximal tumor SUV group (58.1% vs 26.8%, respectively; P < .001). Similar results were obtained for the maximal tumor SUV/normal liver maximal SUV ratio (<2 vs ≥2) concerning progression, death, and extrahepatic metastasis. Metabolic activity may be useful not only in predicting prognosis and treatment responses, but also in establishing optimal treatment plans in locally advanced HCC. Copyright © 2011 American Cancer Society.

Pertuzumab and Erlotinib in Patients With Relapsed Non-Small Cell Lung Cancer: A Phase II Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging

PubMed Central

Mileshkin, Linda; Townley, Peter; Gitlitz, Barbara; Eaton, Keith; Mitchell, Paul; Hicks, Rodney; Wood, Katie; Amler, Lucas; Fine, Bernard M.; Loecke, David; Pirzkall, Andrea

2014-01-01

Background. Combination blockade of human epidermal growth factor receptor (HER) family signaling may confer enhanced antitumor activity than single-agent blockade. We performed a single-arm study of pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, and erlotinib in relapsed non-small cell lung cancer (NSCLC). Methods. Patients received pertuzumab (840-mg loading dose and 420-mg maintenance intravenously every 3 weeks) and erlotinib (150-mg or 100-mg dose orally, daily). The primary endpoint was response rate (RR) by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) at day 56 in all patients and those with EGFR wild-type tumors. Results. Of 41 patients, 28 (68.3%) experienced treatment-related grade ≥3 adverse events, including pneumatosis intestinalis (3 patients), resulting in early cessation of enrollment. Tissue samples from 32 patients showed mutated EGFR status in 9 of 41 (22%) and wild-type EGFR in 23 of 41 (56%). The FDG-PET RR for patients with assessments at day 56 was 19.5% in all patients (n = 41) and 8.7% in patients with wild-type EGFR NSCLC (n = 23). Investigator-assessed computed tomography RR at day 56 was 12.2%. Conclusion. FDG-PET suggests that pertuzumab plus erlotinib is an active combination, but combination therapy was poorly tolerated, which limits its clinical applicability. More research is warranted to identify drug combinations that disrupt HER receptor signaling but that exhibit improved tolerability profiles. PMID:24457379

18F-FDG uptake in the colon is modulated by metformin but not associated with core body temperature and energy expenditure

PubMed Central

Bahler, Lonneke; Holleman, Frits; Chan, Man-Wai; Booij, Jan; Hoekstra, Joost B.; Verberne, Hein J.

2017-01-01

Purpose Physiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature. Therefore, we aimed to determine whether metformin modifies the metabolic activity of the colon by increasing glucose uptake. Methods In this open label, non-randomized, prospective mechanistic study, we included eight lean and eight overweight males. We measured colonic 18F-FDG uptake on PET-CT, energy expenditure and core body temperature before and after the use of metformin. The maximal colonic 18F-FDG uptake was measured in 5 separate segments (caecum, colon ascendens,—transversum,—descendens and sigmoid). Results The maximal colonic 18F-FDG uptake increased significantly in all separate segments after the use of metformin. There was no significant difference in energy expenditure or core body temperature after the use of metformin. There was no correlation between maximal colonic 18F-FDG uptake and energy expenditure or core body temperature. Conclusion Metformin significantly increases colonic 18F-FDG uptake, but this increased uptake is not associated with an increase in energy expenditure or core body temperature. Although the colon might be an important site of the glucose plasma lowering actions of metformin, this mechanism of action does not explain directly any associated weight loss. PMID:28464031

Brain glucose transport and phosphorylation under acute insulin-induced hypoglycemia in mice: an 18F-FDG PET study.

PubMed

Alf, Malte F; Duarte, João M N; Schibli, Roger; Gruetter, Rolf; Krämer, Stefanie D

2013-12-01

We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Quantitative (18)F-FDG PET combined with the acquisition of real-time arterial input function was performed on mice. Hypoglycemia was induced and maintained by insulin infusion. PET data were analyzed with the 2-tissue-compartment model for (18)F-FDG, and the results were evaluated with Michaelis-Menten saturation kinetics. Glucose clearance from plasma to brain (K1,glc) and the phosphorylation rate constant increased with decreasing plasma glucose (Gp), in particular at a Gp of less than 2.5 mmol/L. Estimated cerebral glucose extraction ratios taking into account an increased cerebral blood flow (CBF) at a Gp of less than 2 mmol/L were between 0.14 and 0.79. CBF-normalized K1,glc values were in agreement with saturation kinetics. Phosphorylation rate constants indicated intracellular glucose depletion at a Gp of less than 2-3 mmol/L. When brain regions were compared, glucose transport under hypoglycemia was lowest in the hypothalamus. Alterations in glucose transport and phosphorylation, as well as intracellular glucose depletion, under acute hypoglycemia can be modeled by saturation kinetics taking into account an increase in CBF. Distinct transport kinetics in the hypothalamus may be involved in its glucose-sensing function.

Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

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

Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin

2014-09-01

Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detectedmore » unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.« less

18F-fluorodeoxyglucose-positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester disease.

PubMed

Arnaud, Laurent; Malek, Zoulikha; Archambaud, Frédérique; Kas, Aurélie; Toledano, Dan; Drier, Aurélie; Zeitoun, Delphine; Cluzel, Philippe; Grenier, Philippe A; Chiras, Jacques; Piette, Jean-Charles; Amoura, Zahir; Haroche, Julien

2009-10-01

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis. The aim of this study was to assess the value of whole-body scanning with (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in a large cohort of ECD patients from a single center. We retrospectively reviewed all PET scans performed on 31 patients with ECD who were referred to our department between 2005 and 2008. PET images were reviewed by 2 independent nuclear medicine specialist physicians and were compared with other imaging modalities performed within 15 days of each PET scan. Thirty-one patients (10 women and 21 men; median age 59.5 years) underwent a total of 65 PET scans. Twenty-three patients (74%) were untreated at the time of the initial PET scan, whereas 30 of the 34 followup PET scans (88%) were performed in patients who were undergoing immunomodulatory therapy. Comparison of the initial and followup PET scans with other imaging modalities revealed that the sensitivity of PET scanning varied greatly among the different organs studied (range 4.3-100%), while the specificity remained high (range 69.2-100%). Followup PET scans were particularly helpful in assessing central nervous system (CNS) involvement, since the PET scan was able to detect an early therapeutic response of CNS lesions, even before magnetic resonance imaging showed a decrease in their size. PET scanning was also very helpful in evaluating the cardiovascular system, which is a major prognostic factor in ECD, by assessing the heart and the entire vascular tree during a single session. The results of our large, single-center, retrospective study suggest that the findings of a FDG-PET scan may be interesting in the initial assessment of patients with ECD, but its greater contribution is in followup of these patients.

Quantification of Kryptofix 2.2.2 in [18F]fluorine-labelled radiopharmaceuticals by rapid-resolution liquid chromatography.

PubMed

Lao, Yexing; Yang, Cuiping; Zou, Wei; Gan, Manquan; Chen, Ping; Su, Weiwei

2012-05-01

The cryptand Kryptofix 2.2.2 is used extensively as a phase-transfer reagent in the preparation of [18F]fluoride-labelled radiopharmaceuticals. However, it has considerable acute toxicity. The aim of this study was to develop and validate a method for rapid (within 1 min), specific and sensitive quantification of Kryptofix 2.2.2 at trace levels. Chromatographic separations were carried out by rapid-resolution liquid chromatography (Agilent ZORBAX SB-C18 rapid-resolution column, 2.1 × 30 mm, 3.5 μm). Tandem mass spectra were acquired using a triple quadrupole mass spectrometer equipped with an electrospray ionization interface. Quantitative mass spectrometric analysis was conducted in positive ion mode and multiple reaction monitoring mode for the m/z 377.3 → 114.1 transition for Kryptofix 2.2.2. The external standard method was used for quantification. The method met the precision and efficiency requirements for PET radiopharmaceuticals, providing satisfactory results for specificity, matrix effect, stability, linearity (0.5-100 ng/ml, r(2)=0.9975), precision (coefficient of variation < 5%), accuracy (relative error < ± 3%), sensitivity (lower limit of quantification=0.5 ng) and detection time (<1 min). Fluorodeoxyglucose (n=6) was analysed, and the Kryptofix 2.2.2 content was found to be well below the maximum permissible levels approved by the US Food and Drug Administration. The developed method has a short analysis time (<1 min) and high sensitivity (lower limit of quantification=0.5 ng/ml) and can be successfully applied to rapid quantification of Kryptofix 2.2.2 at trace levels in fluorodeoxyglucose. This method could also be applied to other [18F]fluorine-labelled radiopharmaceuticals that use Kryptofix 2.2.2 as a phase-transfer reagent.

Distinct [18F]THK5351 binding patterns in primary progressive aphasia variants.

PubMed

Schaeverbeke, Jolien; Evenepoel, Charlotte; Declercq, Lieven; Gabel, Silvy; Meersmans, Karen; Bruffaerts, Rose; Adamczuk, Kate; Dries, Eva; Van Bouwel, Karen; Sieben, Anne; Pijnenburg, Yolande; Peeters, Ronald; Bormans, Guy; Van Laere, Koen; Koole, Michel; Dupont, Patrick; Vandenberghe, Rik

2018-06-26

To assess the binding of the PET tracer [ 18 F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology. The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [ 18 F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [ 18 F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction. Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [ 18 F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [ 18 F]THK5351 scans without partial volume correction revealed similar results. [ 18 F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [ 18 F]THK5351 binding correlates with the severity of clinical

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

PubMed

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

2018-01-01

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

Significant suppression of myocardial (18)F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet.

PubMed

Kobayashi, Yasuhiro; Kumita, Shin-ichiro; Fukushima, Yoshimitsu; Ishihara, Keiichi; Suda, Masaya; Sakurai, Minoru

2013-11-01

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a useful tool for evaluating inflammation. Because, myocardial-FDG uptake occurs with diverse physiology, it should be suppressed during evaluation of myocardial inflammation by FDG-PET/CT. Diets inducing fat-based metabolism, such as a low-carbohydrate, high-fat diet (LCHF), are used in uptake-suppression protocols. However, a complete suppression of myocardial-FDG uptake has not been established. Hence, we assessed the efficacy of 24-h carbohydrate restriction along with an LCHF diet compared to that of the conventional protocol in suppressing myocardial-FDG uptake and also compared fat and glucose metabolism between these protocols. Fourteen healthy volunteers agreed to undergo >24-h carbohydrate restriction (glucose, <10g) and drank an LCHF beverage an hour before FDG administration. A scan performed under conventional fasting protocol served as the control. The maximal standardized uptake values (SUVmax) of the left ventricular (LV) myocardium, and left atrium lumen (blood pool), liver, and lung fields as background, were measured. Blood sugar, free fatty acids (FFAs), insulin, and triglyceride concentrations were measured just before FDG injection and compared between the 2 protocols. Global LV myocardial uptake was significantly lower with the diet-preparation protocol (SUVmax 1.31 [1.15-1.49] vs. 2.98 [1.76-6.43], p=0.001). Target-to-background ratios [myocardium-to-blood ratio (MBR), myocardium-to-lung ratio (MLR), and myocardium-to-liver ratio (MLvR)] were also significantly lower with the diet-preparation protocol [MBR: 0.75 (0.68-0.84) vs. 1.63 (0.98-4.09), p<0.001; MLR: 1.87 (1.53-2.47) vs. 4.54 (2.53-12.78), p=0.004; MLvR: 0.48 (0.44-0.56) vs. 1.11 (0.63-2.32), p=0.002]. Only insulin levels were significantly different between the subjects in each protocol group (11.3 [6.2-15.1] vs. 3.9 [2.9-6.2]). Carbohydrate restriction together with an LCHF supplement

Primary central nervous system lymphoma in an human immunodeficiency virus-infected patient mimicking bilateral eye sign in brain seen in fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography.

PubMed

Kamaleshwaran, Koramadai Karuppusany; Thirugnanam, Rajasekar; Shibu, Deepu; Kalarikal, Radhakrishnan Edathurthy; Shinto, Ajit Sugunan

2014-04-01

Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) has proven useful in the diagnosis, staging, and detection of metastasis and posttreatment monitoring of several malignancies in human immunodeficiency virus (HIV)-infected patients. It also has the ability to make the important distinction between malignancy and infection in the evaluation of central nervous system (CNS) lesions, leading to the initiation of the appropriate treatment and precluding the need for invasive biopsy. We report an interesting case of HIV positive 35-year-old woman presented with headache, disorientation, and decreased level of consciousness. She underwent whole body PET/CT which showed multiple lesions in the cerebrum which mimics bilateral eye in brain. A diagnosis of a primary CNS lymphoma was made and patient was started on chemotherapy.

PET quantification of 5-HT2A receptors in the human brain: a constant infusion paradigm with [18F]altanserin.

PubMed

van Dyck, C H; Tan, P Z; Baldwin, R M; Amici, L A; Garg, P K; Ng, C K; Soufer, R; Charney, D S; Innis, R B

2000-02-01

[18F]altanserin has been used to label serotonin 5-HT2A receptors, which are believed to be important in the pathophysiology of schizophrenia and depression. The purpose of this study was to test the feasibility of a constant infusion paradigm for equilibrium modeling of [18F]altanserin with PET. Kinetic modeling with [18F]altanserin may be hampered by the presence of lipophilic radiometabolites observed in plasma after intravenous administration. Eight healthy volunteers were injected with [18F]altanserin as a bolus (208+/-9 MBq [5.62+/-0.25 mCi]) plus constant infusion (65+/-3 MBq/h [1.76+/-0.08 mCi/h]) ranging from 555 to 626 min (615+/-24 min) after injection. PET acquisitions (10-20 min) and venous blood sampling were performed every 30-60 min throughout the infusion period. Linear regression analysis revealed that time-activity curves for both brain activity and plasma [18F]altanserin and metabolite concentrations stabilized after about 6 h. This permitted equilibrium modeling and estimation of V3' (ratio of specific uptake [cortical-cerebellar] to total plasma parent concentration after 6 h). Values of V3' ranged from 1.57+/-0.38 for anterior cingulate cortex to 1.02+/-0.39 for frontal cortex. The binding potential V3 (ratio of specific uptake to free plasma parent concentration after 6 h, using group mean f1) was also calculated and ranged from 169+/-41 for anterior cingulate cortex to 110+/-42 for frontal cortex. From 6 h onward, the rate of change for V3' and V3 was only 1.11+/-1.69 %/h. These results demonstrate the feasibility of equilibrium imaging with [18F]altanserin over more than 5 radioactive half-lives and suggest a method to overcome difficulties associated with lipophilic radiolabeled metabolites. The stability in V3 and V3' once equilibrium is achieved suggests that a single PET acquisition obtained at 6 h may provide a reasonable measure of 5-HT2A receptor density.

Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2.

PubMed

Moriguchi, Sho; Takano, Harumasa; Kimura, Yasuyuki; Nagashima, Tomohisa; Takahata, Keisuke; Kubota, Manabu; Kitamura, Soichiro; Ishii, Tatsuya; Ichise, Masanori; Zhang, Ming-Rong; Shimada, Hitoshi; Mimura, Masaru; Meyer, Jeffrey H; Higuchi, Makoto; Suhara, Tetsuya

2017-12-01

The norepinephrine transporter in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and norepinephrine transporter occupancy in the human brain has not been determined. In this study, we examined norepinephrine transporter occupancy by different doses of duloxetine. We calculated norepinephrine transporter occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n =2). Positron emission tomography scans were performed from 120 to 180 minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second positron emission tomography scan. Norepinephrine transporter occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0% at 60 mg. The estimated dose of duloxetine inducing 50% norepinephrine transporter occupancy was 76.8 mg, and the estimated plasma drug concentration inducing 50% norepinephrine transporter occupancy was 58.0 ng/mL. Norepinephrine transporter occupancy by clinical doses of duloxetine was approximately 30% to 40% in human brain as estimated using positron emission tomography with (S,S)-[18F]FMeNER-D2. © The Author 2017. Published by Oxford University Press on behalf of CINP.

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

PubMed Central

Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

2016-01-01

Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

Metabolic effects of pulmonary obstruction on myocardial functioning: a pilot study using multiple time-point 18F-FDG-PET imaging.

PubMed

Choi, Grace G; Han, Yuchi; Weston, Brian; Ciftci, Esra; Werner, Thomas J; Torigian, Drew; Salavati, Ali; Alavi, Abass

2015-01-01

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the right ventricle (RV) of patients with chronic obstructive pulmonary disease (COPD) and to characterize the variability of 18F-FDG uptake in the RV at different time points following radiotracer administration using PET/computerized tomography (CT). Impaired RV systolic function, RV hypertrophy, and RV dilation are associated with increases in mean pulmonary arterial pressure in patients with COPD. Metabolic changes in the RV using 18F-FDG-PET images 2 and 3 h after tracer injection have not yet been investigated. Twenty-five patients with clinical suspicion of lung cancer underwent 18F-FDG-PET/CT imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUVs) and volumes of RV were recorded from transaxial sections to quantify the metabolic activity. The SUV of RV was higher in patients with COPD stages 1-3 as compared with that in patients with COPD stage 0. RV SUV was inversely correlated with FEV1/FVC pack-years of smoking at 1 h after 18F-FDG injection. In the majority of patients, 18F-FDG activity in RV decreased over time. There was no significant difference in the RV myocardial free wall and chamber volume on the basis of COPD status. The severity of lung obstruction and pack-years of smoking correlate with the level of 18F-FDG uptake in the RV myocardium, suggesting that there may be metabolic changes in the RV associated with lung obstruction that can be detected noninvasively using 18F-FDG-PET/CT. Multiple time-point images of the RV did not yield any additional value in this study.

The predictive value of 201Tl rest-redistribution and 18F-fluorodeoxyglucose SPECT for wall motion recovery after recent reperfused myocardial infarction.

PubMed

González, Patricio; Massardo, Teresa; Coll, Claudia; Humeres, Pamela; Sierralta, Paulina; Jofré, M Josefina; Yovanovich, Jorge; Aramburu, Ivonne; Brugère, Solange; Chamorro, Hernán

2004-04-01

201Tl and 18F-FDG are useful for acute myocardial infarction (MI) assessment. The goal of this study was to compare their predictive value for wall motion recovery in the culprit area after a recent reperfused MI using SPECT technique. Forty-one patients (mean age: 56 +/- 12 years) were included, 81% of them male; all were studied within 1-24 days post MI. They underwent angioplasty in 27 cases (12 primary); bypass grafting in 10 cases and successful thrombolysis in 4. SPECT 201Tl injected at rest and redistribution (R-R) and also 18F-FDG, were performed on different days. Processed tomograms were interpreted blinded to clinical or angiographic data. Segmental wall motion assessed with echocardiography at baseline was compared with the 3 month follow up. Sensitivity [Confidence Interval] for 201Tl R-R was 74.6% [60.5-84.5], for FDG it was 82.1% [70.8-90.4]; specificities were 73% [64.3-80.5] and 54.8% [45.6-63.7], respectively. 18F-FDG tended to be more sensitive than 201Tl R-R, but the latter was more specific (p < 0.0004). Both 201Tl RR and 18F-FDG presented high negative predictive value (p: ns). In recent MI, SPECT 201Tl R-R is a valuable and widely available technique for viability detection, with similar sensitivity and significant better specificity than SPECT 18F-FDG.

Specific α4β2 Nicotinic Acetylcholine Receptor Binding of [F-18]Nifene in the Rhesus Monkey

PubMed Central

Hillmer, A.T.; Wooten, D.W.; Moirano, J.; Slesarev, M.; Barnhart, T.E.; Engle, J.W.; Nickles, R.J.; Murali, D.; Schneider, M.; Mukherjee, J.; Christian, B.T.

2013-01-01

Objective [F-18]Nifene is a PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChR) in the brain. This work assesses the in vivo binding and imaging characteristics of [F-18]nifene in rhesus monkeys for the development of PET experiments examining nAChR binding. Methods Dynamic PET imaging experiments with [F-18]nifene were acquired in 4 anesthetized macaca mulatta (rhesus) monkeys using a microPET P4 scanner. Data acquisition was initiated with a bolus injection of 109 ± 17 MBq [F-18]nifene and the time course of the radioligand in the brain was measured for up to 120 minutes. For two experiments, a displacement dose of (−)nicotine (0.03 mg/kg, i.v.) was given 45–60 minutes post injection and followed 30 minutes later with a second [F-18]nifene injection to measure radioligand nondisplaceable uptake. Time activity curves were extracted in the regions of the antereoventral thalamus (AVT), lateral geniculate nucleus region (LGN), frontal cortex, and the cerebellum (CB). Results The highest levels of [F-18]nifene uptake were observed in the AVT and LGN. Target-to-CB ratios reached maximum values of 3.3 ± 0.4 in the AVT and 3.2 ± 0.3 in the LG 30–45 minutes post-injection. Significant binding of [F-18]nifene was observed in the subiculum, insula cortex, temporal cortex, cingulate gyrus, frontal cortex, striatum, and midbrain areas. The (−)nicotine displaced bound [F-18]nifene to near background levels within 15 minutes post-drug injection. No discernable displacement was observed in the CB, suggesting its potential as a reference region. Logan graphical estimates using the CB as a reference region yielded binding potentials (BPND) of 1.6 ± 0.1 in the AVT, and 1.3 ± 0.1 in the LGN. The post-nicotine injection displayed uniform nondisplaceable uptake of [F-18]nifene throughout gray and white brain matter. Conclusions [F-18]Nifene exhibits rapid equilibration and a moderately high target to background binding profile in the α4�

Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics.

PubMed

Yang, Yanping; Wang, Xuedan; Yang, Hui; Fu, Hualong; Zhang, Jinming; Zhang, Xiaojun; Dai, Jiapei; Zhang, Zhiyong; Lin, Chunping; Guo, Yuzhi; Cui, Mengchao

2016-11-07

This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)- 18 F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with K i values ranging from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution, and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20. Notably, (S)-[ 18 F]28 possessed high binding potency (K i = 7.6 nM) and exceptional brain kinetics (9.46% ID/g at 2 min, brain 2min /brain 60min = 27.8) that is superior to well-established [ 18 F]AV45. The excellent pharmacokinetics and low nonspecific binding of (S)-[ 18 F]28 were testified by dynamic PET/CT scans in monkey brains. In addition, (S)-[ 18 F]28 clearly labeled Aβ plaques both in vitro and ex vivo. These results might qualify (S)-[ 18 F]28 to detect Aβ plaques with high signal-to-noise ratio.

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

PubMed Central

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

2010-01-01

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

Potential Use of {sup 18}F-fluorodeoxyglucose Positron Emission Tomography–Based Quantitative Imaging Features for Guiding Dose Escalation in Stage III Non-Small Cell Lung Cancer

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

Fried, David V., E-mail: dvfried@mdanderson.org; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas; Mawlawi, Osama

2016-02-01

Purpose: To determine whether previously identified quantitative image features (QIFs) based on {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS). Methods and Materials: Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log-rank test to determine whether there was a difference in OS and PFS betweenmore » patients treated with 60 to 70 Gy and those receiving 74 Gy. Results: In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co-occurrence matrix energy. Conclusions: FDG-PET–based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation.« less

Positron emission tomography with [ 18F]-FDG in oncology

NASA Astrophysics Data System (ADS)

Talbot, J. N.; Petegnief, Y.; Kerrou, K.; Montravers, F.; Grahek, D.; Younsi, N.

2003-05-01

Positron Emission Tomography (PET) is a several decade old imaging technique that has more recently demonstrated its utility in clinical applications. The imaging agents used for PET contain a positron emmiter coupled to a molecule that drives the radionuclide to target organs or to tissues performing the targetted biological function. PET is then part of functional imaging. As compared to conventional scintigraphy that uses gamma photons, the coincidence emission of two 511 keV annihilation photons in opposite direction that finally results from by beta plus decay makes it possible for PET to get rid of the collimators that greatly contribute to the poor resolution of scintigraphy. In this article, the authors describe the basics of physics for PET imaging and report on the clinical performances of the most commonly used PET tracer: [ 18F]-fluorodeoxyglucose (FDG). A recent and promising development in this field is fusion of images coming from different imaging modalities. New PET machines now include a CT and this fusion is therefore much easier.

Silastic injection for vocal fold medialization resulting in a false-positive finding on F18 FDG-PET/CT.

PubMed

Mahfouz, Ayman; Naji, Meeran; Mok, Wing Yan; Taghi, Ali S; Win, Zarni

2015-09-01

A false-positive uptake of F18-fluorodeoxyglucose (FDG) on positron-emission tomography/computed tomography (PET/CT) can result in confusion and misinterpretation of scans. Such uptakes have been previously described after injection of polytetrafluoroethylene (Teflon) into the vocal folds. Similarly, vocal fold injection of silicone elastomer (Silastic) can result not only in a false-positive FDG uptake on PET/CT, but also in chronic inflammation. We report a case of increased FDG uptake in a vocal fold after Silastic injection that was misinterpreted as a malignancy in a 70-year-old woman who had metastatic carcinoma of the stomach.

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

PubMed

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

2018-05-01

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

18F-FDG or 3'-deoxy-3'-18F-fluorothymidine to detect transformation of follicular lymphoma.

PubMed

Wondergem, Marielle J; Rizvi, Saiyada N F; Jauw, Yvonne; Hoekstra, Otto S; Hoetjes, Nikie; van de Ven, Peter M; Boellaard, Ronald; Chamuleau, Martine E D; Cillessen, Saskia A G M; Regelink, Josien C; Zweegman, Sonja; Zijlstra, Josée M

2015-02-01

Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that (18)F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) might be superior to (18)F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a head-to-head comparison of (18)F-FDG and (18)F-FLT in patients with FL and TF. (18)F-FDG and (18)F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUVmax), defined as the lymph node with the highest uptake per patient, and SUVrange, defined as the difference between the SUVmax of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm(3) (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of (18)F-FDG or (18)F-FLT. To determine the discriminative ability of SUVmax and SUVrange of both tracers for TF, receiver-operating-characteristic curve analysis was performed. The highest SUVmax was significantly higher for TF than FL for both (18)F-FDG and (18)F-FLT (P < 0.001). SUVrange was significantly higher for TF than FL for (18)F-FDG (P = 0.029) but not for (18)F-FLT (P = 0.075). The ability of (18)F-FDG to discriminate between FL and TF was superior to that of (18)F-FLT for both the highest SUVmax (P = 0.039) and the SUVrange (P = 0.012). The cutoff value for the highest SUVmax of (18)F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For (18)F-FLT, these values were

Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data.

PubMed

Pagani, Marco; Giuliani, Alessandro; Öberg, Johanna; De Carli, Fabrizio; Morbelli, Silvia; Girtler, Nicola; Arnaldi, Dario; Accardo, Jennifer; Bauckneht, Matteo; Bongioanni, Francesca; Chincarini, Andrea; Sambuceti, Gianmario; Jonsson, Cathrine; Nobili, Flavio

2017-07-01

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18 F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18 F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Binding of 2-[18F]fluoro-CP-118,954 to mouse acetylcholinesterase: microPET and ex vivo Cerenkov luminescence imaging studies.

PubMed

Kim, Dong Hyun; Choe, Yearn Seong; Choi, Joon Young; Lee, Kyung-Han; Kim, Byung-Tae

2011-05-01

Acetylcholinesterase (AChE) has been an important cholinergic factor for the diagnosis of Alzheimer's disease (AD), because of reduced AChE activity in the postmortem brains of AD patients. We previously developed 5,7-dihydro-3-(2-(1-(2-[(18)F]fluorobenzyl)-4-piperidinyl)ethyl)-6H-pyrrolo(3,2,f)-1,2-benzisoxazol-6-one (2-[(18)F]fluoro-CP-118,954) for in vivo studies of AChE in mice. In the present study, we automated the synthesis of 2-[(18)F]fluoro-CP-118,954 for the routine use and evaluated the radioligand by microPET and ex vivo Cerenkov luminescence imaging of mouse AChE. 4-[(18)F]Fluoro-donepezil, another AChE inhibitor, was used for comparison. Automated syntheses of 2-[(18)F]fluoro-CP-118,954 and 4-[(18)F]fluoro-donepezil resulted in high radiochemical yields (25-33% and 30-40%) and high specific activity (27.1-35.4 and 29.7-37.3 GBq/μmol). Brain microPET images of two ICR mice injected with 2-[(18)F]fluoro-CP-118,954 demonstrated high uptake in the striatum (ROI analysis: 5.1 %ID/g for the first 30 min and 4.1 %ID/g for another 30 min), and a blocking study with injection of CP-118,954 into one of the mice at 30 min after radioligand injection led to complete blocking of radioligand uptake in the striatum (ROI analysis: 1.9 %ID/g), whereas (18)F-labeled donepezil did not show specific uptake in the striatum. In another set of experiments, the brain tissues (striatum, parietal cortex, frontal cortex and cerebellum) were excised after brain microPET/CT imaging of mouse injected with 2-[(18)F]fluoro-CP-118,954, and a high striatal uptake was also detected in ex vivo optical and microPET images (ROI analysis: 1.4 %ID/g) and in γ-counting data (2.1 %ID/g at 50 min post-injection) of the brain tissues. Taken together, these results demonstrated that 2-[(18)F]fluoro-CP-118,954 specifically binds to AChE in mouse brains. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-06-01

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

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

PubMed

Knešaurek, Karin; Machac, Josef

2006-10-31

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

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

No-carrier-added (/sup 18/F)-N-methylspiroperidol

DOEpatents

Shiue, C.Y.; Fowler, J.S.; Wolf, A.P.

1985-10-04

The present invention is directed to the synthesis of a radioligand, labeled with a positron emitting radionuclide which is suitable for dynamic studies in humans using positron emission transaxial tomography. No-carrier-added (NCA) (/sup 18/F)-N-methylspiroperiodl is prepared from four different sustrates: p-nitrobenzonitrile, cyclopropyl p-nitrophenyl ketone, p-cyclopropanoyl-N,N,N-trimethylanilinium iodide and p-cyclopropanoyl-N,N,N-trimethylanilinium perchlorate. The process for the production of NCA (/sup 18/F)-N-methylspiroperidol is a nucleophilic aromatic substitution reaction. Furthermore, the compound of this invention is shown to be effective as a new drug of choice for in vivo examination of dopamine binding sites in a human brain. In particular, this drug is primarily useful in the noninvasive technique of positron emission transaxial tomography (PETT).

Assessment of early response to imatinib 800 mg after 400 mg progression by ¹⁸F-fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal tumors.

PubMed

Chacón, Matías; Eleta, Martín; Espindola, Adriel Rodríguez; Roca, Enrique; Méndez, Guillermo; Rojo, Sandra; Pupareli, Carmen

2015-01-01

Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients. After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS). EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05). The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

Effect of (18)F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses.