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

Energy Technology Data Exchange (ETDEWEB)

Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

2013-10-15

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

Alpha-fetoprotein and (18)F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation.

Science.gov (United States)

Hong, Geun; Suh, Kyung-Suk; Suh, Suk-Won; Yoo, Tae; Kim, Hyeyoung; Park, Min-Su; Choi, YoungRok; Paeng, Jin Chul; Yi, Nam-Joon; Lee, Kwang-Woong

2016-04-01

Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Synthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate: a novel bifunctional {sup 18}F-labelling agent

Energy Technology Data Exchange (ETDEWEB)

Wuest, F.; Mueller, M.; Bergmann, R. [Inst. fuer Bioanorganische und Radiopharmazeutische Chemie, FZ-Rossendorf e.V., Dresden (Germany)

2004-07-01

The one-step radiosynthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate {sup 18}F-7 as a novel bifunctional {sup 18}F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate {sup 18}F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of > 95% after solid-phase-extraction. Coupling of compound {sup 18}F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[{sup 18}F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea {sup 18}F-8 in a high radiochemical yield of > 90%. Stability studies of thiourea {sup 18}F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when {sup 18}F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea {sup 18}F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination. (orig.)

18F-fluoromisonidazole (FMISO) and 18F-fluorodeoxyglucose (FDG) PET in patients undergoing radiotherapy or chemotherapy following surgery for high-grade glioma

International Nuclear Information System (INIS)

Lee, S. T.

2009-01-01

Full text:Background: Tumour hypoxia is associated with disease progression and resistance to therapy. High grade cerebral gliomas have a poor outcome despite advancements in chemotherapy and radiotherapy. 18F-fluoromisonidazole (18F-FMISO) concentrates in hypoxic cells and is associated with tumour grade in gliomas. The aim of this study was to compare the patterns of uptake of 18F-FDG PET and 18F-FMISO PET post-surgery with MRI and areas of recurrence post-radiotherapy. Methods: Patients with high grade cerebral glioma were recruited into this prospective study. All patients had post-surgical, pre-radiotherapy 18F-FDG, 18F-FMISO and MRI scans, which were all repeated 4-6 weeks post-completion to radiotherapy. The patients were followed-up clinically three monthly and re-imaged if indicated. Results: Ten patients were enrolled in this study, mean age 62 years (range 55-69 years), who all had pre-radiotherapy scans performed. Seven patients had scans done pre- and post-radiotherapy, with 3 patients with only pre-therapy scans. Nine patients had significant FMISO uptake and 8 patients demonstrated abnormal FDG uptake. The areas of FMISO uptake on pre-radiotherapy scans correlated with the most abnormal areas of contrast-enhancement on pre-treatment MRI and areas of locally recurrent disease on post-treatment MRI in eight patients. Nine patients had locally recurrent disease on follow-up MRI. FMISO was more predictive of tumour recurrence compared to FDG. Conclusion: Post-surgical 18F-FMISO PET in patients with cerebral glioma is more predictive of areas of recurrent disease compared to 18F-FDG PET.

Intraoperative detection of 18F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria

International Nuclear Information System (INIS)

Povoski, Stephen P; Chapman, Gregg J; Murrey, Douglas A; Lee, Robert; Martin, Edward W; Hall, Nathan C

2013-01-01

Intraoperative detection of 18 F-FDG-avid tissue sites during 18 F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of 18 F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. Of 58 patients undergoing 18 F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine 18 F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each 18 F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2–15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0–2.1) and 1.0 (± 0, range 1.0–1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18 F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography.

Science.gov (United States)

Lin, Kuo-Shyan; Ding, Yu-Shin; Kim, Sung-Won; Kil, Kun-Eek

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[alpha-(2-(2-[(18)F]fluoroethoxy)phenoxy)benzyl]morpholine ([(18)F]FRB) and its tetradeuterated form [(18)F]FRB-D(4), analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[alpha-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [(18)F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[alpha-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [(18)F]FRB and [(18)F]FRB-D(4) via the following three-step procedure: (1) formation of 1-bromo-2-[(18)F]fluoroethane ([(18)F]BFE or [(18)F]BFE-D(4)) by nucleophilic displacement of 2-bromoethyl triflate (or D(4) analog) with no-carrier added [(18)F]F(-) in THF; (2) reaction of [(18)F]BFE (or [(18)F]BFE-D(4)) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [(18)F]FRB and [(18)F]FRB-D(4) were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/micromol (EOB). The results of the whole-body biodistribution studies with (S,S)-[(18)F]FRB-D(4) were similar to those with (S,S)-[(18)F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also showed that (S,S)-[(18)F]FRB-D(4) may be a potentially useful ligand for imaging NET with PET.

18F half-life measurement using a high-purity germanium detector

International Nuclear Information System (INIS)

Han, Jubong; Lee, K.B.; Park, T.S.; Lee, J.M.; Oh, P.J.; Lee, S.H.; Kang, Y.S.; Ahn, J.K.

2012-01-01

The half-life of 18 F has been measured using HPGe detectors with a 137 Cs reference source. The counting ratio of 511 keV γ-rays from 18 F to 622 keV γ-rays from 137 Cs was fitted for the half-life with a weighted least-square method. Uncertainties due to the systematic effects arising from the measurement of a high activity 18 F source were studied in detail. The half-life of 18 F was found to be (109.72±0.19) min. The result is in a good agreement with the recommended value of (109.728±0.019) min evaluated at the Laborotaire National Henri Becquerel (LNHB). - Highlights: ► The 18 F half-life was measured with a reference source and without it using HPGe detectors. ► We found the systematic effect ‘activity dynamic range effect’ by monitoring the counts of the reference source. ► This activity dynamic range effect was corrected by using the reference source method. ► The 18 F half-life using the reference source method was in a good agreement with the recommended value of LNHB.

Comparison of {sup 18}F-FET and {sup 18}F-FDG PET in brain tumors

Energy Technology Data Exchange (ETDEWEB)

Pauleit, Dirk; Stoffels, Gabriele [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Bachofner, Ansgar [Clinic of Nuclear Medicine, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Floeth, Frank W.; Sabel, Michael [Department of Neurosurgery, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Herzog, Hans; Tellmann, Lutz [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Jansen, Paul [Institute of Advanced Simulation, Forschungszentrum Juelich, D-52425 Juelich (Germany); Reifenberger, Guido [Department of Neuropathology, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Hamacher, Kurt; Coenen, Heinz H. [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Langen, Karl-Josef [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany)], E-mail: k.j.langen@fz-juelich.de

2009-10-15

The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [{sup 18}F]-fluorodeoxyglucose ({sup 18}F-FDG) and O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) in patients with brain lesions suspicious of cerebral gliomas. Methods: Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq {sup 18}F-FET, a first PET scan ({sup 18}F-FET scan) was performed. Thereafter, 240 MBq {sup 18}F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ({sup 18}F-FET/{sup 18}F-FDG scan). The cerebral accumulation of {sup 18}F-FDG was calculated by decay corrected subtraction of the {sup 18}F-FET scan from the {sup 18}F-FET/{sup 18}F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. Results: Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased {sup 18}F-FET uptake (>normal brain) in 86% and increased {sup 18}F-FDG uptake (>white matter) in 35%. {sup 18}F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with {sup 18}F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with {sup 18}F-FET in 76% and with {sup 18}F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with {sup 18}F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both

Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

Science.gov (United States)

Beheshti, Mohsen; Rezaee, Alireza; Geinitz, Hans; Loidl, Wolfgang; Pirich, Christian; Langsteger, Werner

2016-10-01

18 F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18 F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18 F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18 F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18 F-NaF PET/CT is a highly sensitive method, but 18 F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Synthesis of 6-[18F] and 4-[18F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation

International Nuclear Information System (INIS)

Namavari, Mohammad; Satyamurthy, N.; Phelps, M.E.; Barrio, J.R.; California Univ., Los Angeles, CA

1993-01-01

The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative with [ 18 F]F 2 and [ 18 F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[ 18 F]fluoro-L-m-tyrosine in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[ 18 F]fluoro-L-m-tyrosine was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative using [ 18 F]F 2 . The structural analyses of precursors, intermediates, and the final products (after 18 F decay), were carried out by 1 H, 13 C, 19 F, 119 Sn-NMR and high resolution mass spectroscopy. (author)

In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide

International Nuclear Information System (INIS)

Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr.

1991-01-01

Two [ 18 F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[ 18 F]- or 4-[ 18 F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies

Inelastic Branch of the Stellar Reaction $^{14}$O$(\\alpha,p)^{17}$F

CERN Multimedia

Hass, M; Van duppen, P L E

2002-01-01

We propose to use the upgraded REX-ISOLDE beam energy to study the astrophysically important $^{14}$O($\\alpha$, p)$^{17}$F reaction in time reverse kinematics. In particular, we will use the highly efficient miniball + CD detection system to measure the previously undetermined inelastic proton branch of the 1$^-$ state at 6.15 MeV in $^{18}$Ne. This state dominates the reaction rate under X-ray burster conditions.

Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Lin, K.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Ding, Y.-S. [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States)]. E-mail: ding@bnl.gov; Kim, Sung-Won [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States); Kil, Kun-Eek [Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973 (United States)

2005-05-01

Racemic and enantiomerically pure ((S,S) and (R,R)) 2-[{alpha}-(2-(2-[{sup 18}F]fluoroethoxy)phenoxy)benzyl]morpholine ([{sup 18}F]FRB) and its tetradeuterated form [{sup 18}F]FRB-D{sub 4}, analogs of the highly selective norepinephrine reuptake inhibitor reboxetine (2-[{alpha}-(2-ethoxyphenoxy)benzyl]morpholine, RB), have been synthesized for studies of norepinephrine transporter (NET) system with positron emission tomography (PET). The [{sup 18}F]fluorinated precursor, (S,S)/(R,R)-N-tert-butyloxycarbonyl-2-[{alpha}-(2-hydroxyphenoxy)benzyl] morpholine ((S,S)/(R,R)-N-Boc-desethylRB), was prepared by the N-protection of (S,S)/(R,R)-2-[{alpha}-(2-hydroxyphenoxy)benzyl]morpholine ((S,S)/(R,R)-desethylRB) with a tert-butyloxycarbonyl (Boc) group followed by enantiomeric resolution with chiral HPLC to provide both (S,S) and (R,R) enantiomers with >99% enantiomeric purity. These compounds were then used for radiosynthesis to prepare enantiomerically pure [{sup 18}F]FRB and [{sup 18}F]FRB-D{sub 4} via the following three-step procedure: (1) formation of 1-bromo-2-[{sup 18}F]fluoroethane ([{sup 18}F]BFE or [{sup 18}F]BFE-D{sub 4}) by nucleophilic displacement of 2-bromoethyl triflate (or D{sub 4} analog) with no-carrier added [{sup 18}F]F{sup -} in THF; (2) reaction of [{sup 18}F]BFE (or [{sup 18}F]BFE-D{sub 4}) with N-Boc-desethylRB in DMF in the presence of excess base; and (3) deprotection with trifluoroacetic acid. The racemates, (S,S) and (R,R) enantiomers of [{sup 18}F]FRB and [{sup 18}F]FRB-D{sub 4} were obtained in 11-27% (decay corrected to the end of bombardment, EOB) in 120-min synthesis time with a radiochemical purity of >98% and specific activities of 21-48 GBq/{mu}mol (EOB). The results of the whole-body biodistribution studies with (S,S)-[{sup 18}F]FRB-D{sub 4} were similar to those with (S,S)-[{sup 18}F]FRB but showed relatively faster blood clearance and no significant in vivo defluorination. Positron emission tomography studies in baboon brain also

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

Science.gov (United States)

Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

2017-01-01

The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.

Science.gov (United States)

Way, Jenilee Dawn; Wuest, Frank

2014-02-01

4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.

High Yield F-18 Target for KOTRON-13 Cyclotron

International Nuclear Information System (INIS)

Lee, W. K.; Song, J. Y.; Park, J. Y.; Jung, K. I.; Chae, S. K.

2009-01-01

Currently the domestic radiation market for medical diagnosis witnesses a high increase of the use of PET/CT for the purpose of cancer diagnosis, and the cases of cancer diagnosis using PET/CT increase by geometric progression every year. In case of domestic practice, full body scan is taken by using FDG medical isotope medicines mainly using F-18, but the necessity of various medical radioactive isotopes according to each medical purpose is increasing. F-18 output yield is directly proportional to energy of protons and beam current, and has correlation with heat production rate in case of target and decides the function of target in accordance with the efficiency of a cooling device. At present, in case of most F-18 target, when one irradiates beam in O-18 water of about 0.2∼5mL, one has to apply heat of over 300W, a high thermal energy per unit area is irradiated in target, which is easily damaged, and it has limitation in beam current. Currently, in case of commercial target, about 2,000W beam current is the maximum value, and in case of double-grid target developed by Korea Institute of Radiological and Medical Sciences in 2004, it was designed to stand up to about 1,000W theoretically, but in reality it can irradiate lower beam current than this because of the shortage of cooling efficiency. In general, the irradiation strength to produce radioactive isotopes given in the heat emission by target substance currently is limited to 50μA against target substance irradiated in 1.6mL. However, current KOTRON-13 cyclotron can accelerate proton beam with a high scope of strength marking 100μA thru 120μA by a continuous development. Therefore, it doesn't fully function compared with that of proton beam of KOTRON-13 cyclotron. The solution about this is to get over the problem of cooling target substance of cavity in the production system of radioactive isotopes. Especially, one has to develop the method to cool target substance, and provide higher F-18 yield than

{alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

Energy Technology Data Exchange (ETDEWEB)

Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

2011-02-15

We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

Re(CO)3([18F]FEDA), a novel 18F PET renal tracer: Radiosynthesis and preclinical evaluation.

Science.gov (United States)

Lipowska, Malgorzata; Jarkas, Nashwa; Voll, Ronald J; Nye, Jonathon A; Klenc, Jeffrey; Goodman, Mark M; Taylor, Andrew T

2018-03-01

Our previous work demonstrated that the 99m Tc renal tracer, 99m Tc(CO) 3 (FEDA) ( 99m Tc-1), has a rapid clearance comparable in rats to that of 131 I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99m Tc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18 F renal imaging agent, Re(CO) 3 ([ 18 F]FEDA) ( 18 F-1). Our goal was to develop an efficient one-step method for the preparation of 18 F-1 and to compare its pharmacokinetic properties with those of 131 I-OIH in rats. 18 F-1 was prepared by the nucleophilic 18 F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131 I-OIH as an internal control and by dynamic PET/CT imaging. Plasma protein binding (PPB) and erythrocyte uptake (RCB) were determined and the urine was analyzed for metabolites. 18 F-1 was efficiently prepared as a single species with high radiochemical purity (>99%) and it displayed high radiochemical stability in vitro and in vivo. PPB was 87% and RCB was 21%. Biodistribution studies confirmed rapid renal extraction and high specificity for renal excretion, comparable to that of 131 I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of 131 I-OIH, was 92% and 95% at 10 and 60 min, respectively. All other organs (heart, spleen, lungs) showed a negligible tracer uptake (F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [ 18 F]fluoride. 18 F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of 131 I-OIH and high in vivo radiochemical stability. Not only is 18 F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous 18 F/ 99m Tc renal imaging agents with almost identical structures and comparable

A comparison of [/sup 18/F]spiroperidol, [/sup 18/F]benperidol and [/sup 18/F] haloperidol kinetics in baboon brain

International Nuclear Information System (INIS)

Arnett, C.D.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; Logan, J.

1984-01-01

Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-[/sup 18/F]fluorobenzonitrile which was converted to p-[/sup 18/F]fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give [/sup 18/F]spiroperidol ([/sup 18/F]SP), [/sup 18/F]benperidol ([/sup 18/F]BEN), or [/sup 18/F]haloperidol ([/sup 18/F]HAL). Specific activity ranged from 3 to 6 Ci/μmol. Anesthetized baboons were injected with 6-17 mCi of [/sup 18/F]-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; [/sup 18/F]SP was studied to 8 hr. [/sup 18/F]SP and [/sup 18/F]BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. [/sup 18/F]HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (≅0.07% per ml vs. ≅ 0.02% per ml for [/sup 18/F]SP or [/sup 18/F]BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for [/sup 18/F]SP showed > 90% unchanged drug up to 5 min and ≅ 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of [/sup 18/F]SP to the striatum in the four animals studied. Both [/sup 18/F]SP and [/sup 18/F]BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics

Synthesis of n.c.a. {sup 18}F-fluorinated NMDA- and D{sub 4}-receptor ligands via [{sup 18}F]fluorobenzenes; Traegerarme Synthese {sup 18}F-markierter, ausgewaehlter NMDA- und D{sub 4}-Rezeptorliganden durch Einsatz geeigneter [{sup 18}F]Fluorbenzolderivate

Energy Technology Data Exchange (ETDEWEB)

Ludwig, T

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) {sup 18}F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[{sup 18}F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([{sup 18}F]FPTEA) a dopamine D{sub 4} receptor ligand. In order to synthesize n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the {sup 18}F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic {sup 18}F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([{sup 18}F]fluoroaryloxy)alkylamines via n.c.a. 4-[{sup 18}F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [{sup 18}F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene proved advantageous in comparison to direct use of 4-[{sup 18}]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [{sup 18}F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[{sup 18}F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene, [{sup 18}F]FPTEA was obtained by reaction with 2-(4-tolyloxy

Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

2017-01-15

The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F-NaF

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

International Nuclear Information System (INIS)

Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

2007-01-01

Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

Synthesis of n.c.a. 18F-fluorinated NMDA- and D4-receptor ligands via [18F]fluorobenzenes

International Nuclear Information System (INIS)

Ludwig, T.

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) 18 F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[ 18 F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([ 18 F]FPTEA) a dopamine D 4 receptor ligand. In order to synthesize n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the 18 F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic 18 F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([ 18 F]fluoroaryloxy)alkylamines via n.c.a. 4-[ 18 F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [ 18 F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene proved advantageous in comparison to direct use of 4-[ 18 ]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [ 18 F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[ 18 F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene, [ 18 F]FPTEA was obtained by reaction with 2-(4-tolyloxy)ethylamine in radiochemical yields of about 25-30% in ethanol or 2-butanone

Comparison of three 18F-labeled carboxylic acids with 18F-FDG of the differentiation tumor from inflammation in model mice

International Nuclear Information System (INIS)

Wang, Hongliang; Tang, Ganghua; Hu, Kongzhen; Huang, Tingting; Liang, Xiang; Wu, Zhifang; Li, Sijin

2016-01-01

The aim of this study was to compare the properties and feasibility of the glucose analog, 2- 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG), three short 18 F-labeled carboxylic acids, 18 F-fluoroacetate ( 18 F-FAC), 2- 18 F-fluoropropionic acid ( 18 F-FPA) and 4-( 18 F)fluorobenzoic acid ( 18 F-FBA), for differentiating tumors from inflammation. Biodistributions of 18 F-FAC, 18 F-FPA and 18 F-FBA were determined on normal Kunming mice, and positron emission tomography (PET) imaging with these tracers were performed on the separate tumor-bearing mice model and inflammation mice model in comparison with 18 F-FDG. Biodistribution results showed that 18 F-FAC and 18 F-FPA had similar biodistribution profiles and the slow radioactivity clearance from most tissues excluding the in vivo defluorination of 18 F-FAC, and 18 F-FBA demonstrated a lower uptake and fast clearance in most tissues. PET imaging with 18 F-FDG, 18 F-FAC and 18 F-FPA revealed the high uptake in both tumor and inflammatory lesions. The ratios of tumor-to-inflammation were 1.63 ± 0.28 for 18 F-FDG, 1.20 ± 0.38 for 18 F-FAC, and 1.41 ± 0.33 for 18 F-FPA at 60 min postinjection, respectively. While clear tumor images with high contrast between tumor and inflammation lesion were observed in 18 F-FBA/PET with the highest ratio of tumor-to-inflammation (1.98 ± 0.15). Our data demonstrated 18 F-FBA is a promising PET probe to distinguish tumor from inflammation. But the further modification of 18 F-FBA structure is required to improve its pharmacokinetics

Recoil 18F-chemistry in fluoroalkanes

International Nuclear Information System (INIS)

Linde, K.D. van der.

1982-01-01

This thesis describes the study of the chemical reactions of recoil 18 F-atoms in gaseous fluoromethanes and fluoroethanes. A brief survey of the organic hot atom chemistry is given in Chapter I. Chapter II deals with the experimental procedures used in this investigation. The irradiation facilities, the vapour phase radio-chromatography and the identification, including the synthesis of some fluorocarbons, are described in detail. Chapter III consists of a study on the applicability of perfluoropropene, C 3 F 6 , as scavenger for thermal 18 F-atoms and radicals. Chapters IV, V, VI and VII deal with 18 F-recoil chemistry in gaseous fluoroethanes, using H 2 S as scavenger. Chapter VIII is a short discussion on the hot 18 F-atom based production of 18 F-labeled organic compounds via decay of the intermediate 18 Ne. A target system is proposed for production of this isotope in high energy and ultra high flux particle beams, which possibly would become available in fast breeders and fusion reactors. (Auth.)

A Case of Esophageal Leiomyoma Showing High FDG Uptake on F-18 FDG PET

Energy Technology Data Exchange (ETDEWEB)

Lee, Jai Hyuen [College of Medicine, Cheonan (Korea, Republic of); Ryu, Jin Sook [Asan Medical Center, University of Ulsan College of Medicine (Korea, Republic of)

2008-08-15

An esophageal leiomyoma is the most common benign tumor of the esophagus mainly occurred in intramural portion. Occasionally, it is difficult to discriminate esophageal malignancy from large leiomyoma. Although F-18 FDG PET has been used for differentiating malignant from benign disease, false-positive cases have been reported. Recently, uterine leiomyoma has been reported to have relatively high F-18 FDG uptake in some patients but little is known about how an esophageal leiomyoma might be showed on F-18 FDG PET. We report a case of esophageal leiomyoma that showed high FDG uptake on PET images.

A Case of Esophageal Leiomyoma Showing High FDG Uptake on F-18 FDG PET

International Nuclear Information System (INIS)

Lee, Jai Hyuen; Ryu, Jin Sook

2008-01-01

An esophageal leiomyoma is the most common benign tumor of the esophagus mainly occurred in intramural portion. Occasionally, it is difficult to discriminate esophageal malignancy from large leiomyoma. Although F-18 FDG PET has been used for differentiating malignant from benign disease, false-positive cases have been reported. Recently, uterine leiomyoma has been reported to have relatively high F-18 FDG uptake in some patients but little is known about how an esophageal leiomyoma might be showed on F-18 FDG PET. We report a case of esophageal leiomyoma that showed high FDG uptake on PET images

[18F]FDG PET/CT outperforms [18F]FDG PET/MRI in differentiated thyroid cancer

International Nuclear Information System (INIS)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars; Burg, Matthias Christian; Allkemper, Thomas; Schaefers, Michael

2016-01-01

To evaluate the diagnostic potential of PET/MRI with [ 18 F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [ 18 F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [ 18 F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [ 18 F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [ 18 F]FDG PET/MRI was inferior to low-dose [ 18 F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [ 18 F]FDG PET/MRI was equal to contrast-enhanced neck [ 18 F]FDG PET/CT. Therefore, [ 18 F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast agent is contraindicated. (orig.)

18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

International Nuclear Information System (INIS)

Persico, Marco Giovanni; Buroni, Federica Eleonora; Pasi, Francesca; Lodola, Lorenzo; Aprile, Carlo; Nano, Rosanna; Hodolic, Marina

2016-01-01

Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18 F-methyl-choline ( 18 F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18 F-ethyl-tyrosine ( 18 F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18 F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18 F-FCH and 18 F-FET uptake by human glioblastoma T98G cells. Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10 5 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO 2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18 F-FCH and 18 F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 10 5 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. A significant uptake of 18 F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18 F-FET in comparison to 18 F-FCH was lower by a factor of more than 3, with different kinetic curves. 18 F-FET showed a more rapid initial uptake up to 40 minutes and 18 F-FCH showed a progressive rise reaching a maximum after 90 minutes. 18 F-FCH and 18 F-FET are candidates

[{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 - metabolic considerations

Energy Technology Data Exchange (ETDEWEB)

Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Nics, Lukas [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Ungersboeck, Johanna [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline M. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

2010-05-15

Introduction: Recently, [{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A{sub 3} receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A{sub 3} receptor PET tracers. Methods: In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points (n=3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results: The rate of enzymatic hydrolysis by CES demonstrated Michaelis-Menten constants in a micromolar range (FE-SUPPY, 20.15 {mu}M, and FE-SUPPY:2, 13.11 {mu}M) and limiting velocities of 0.035 and 0.015 {mu}M/min for FE-SUPPY and FE-SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [{sup 18}F]FE-SUPPY was intact compared to 33.1% of [{sup 18}F]FE-SUPPY:2; 30 min pi 30.3% intact [{sup 18}F]FE-SUPPY was found compared to 15.6% [{sup 18}F]FE-SUPPY:2. In brain, [{sup 18}F]FE-SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [{sup 18}F]FE-SUPPY was not observed before 30 min pi Conclusion: Knowing that metabolism in rats is several times faster than in human, we conclude that [{sup 18}F]FE-SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [{sup 18}F]FE-SUPPY.

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

International Nuclear Information System (INIS)

Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

2012-01-01

Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

A Fully Automated Radiosynthesis of [18F]Fluoroethyl-Diprenorphine on a Single Module by Use of SPE Cartridges for Preparation of High Quality 2-[18F]Fluoroethyl Tosylate

Directory of Open Access Journals (Sweden)

Gjermund Henriksen

2013-06-01

Full Text Available We have developed a new method for automated production of 2-[18F]fluoroethyl tosylate ([18F]FETos that enables 18F-alkylation to provide PET tracers with high chemical purity. The method is based on the removal of excess ethylene glycol bistosylate precursor by precipitation and subsequent filtration and purification of the filtrate by means of solid phase extraction cartridges (SPE. The method is integrated to a single synthesis module and thereby provides the advantage over previous methods of not requiring HPLC purification, as demonstrated by the full radiosynthesis of the potent opioid receptor PET tracer [18F]fluoroethyldiprenorphine.

Tritium in [18O]water containing [18F]fluoride for [18F]FDG synthesis

International Nuclear Information System (INIS)

Ito, Shigeki; Saze, Takuya; Sakane, Hitoshi; Ito, Satoshi; Ito, Shinichi; Nishizawa, Kunihide

2004-01-01

The presence of tritium in enriched [ 18 O]water irradiated with 9.6 MeV protons used to produce [ 18 F]fluoride by the 18 O(p, n) 18 F reaction was inferred from the cross sections and threshold energies of the 18 O(p, t) 16 O reaction, and the existence of tritium was confirmed experimentally. Tritium was also detected in both [ 18 O]water recovered for recycling and waste acetonitrile solutions. The purified [ 18 F]FDG was not contaminated with 3 H. The amount of 3 H discharged into the air was far less than the International Basic Safety Standard Level

Safety, pharmacokinetics, metabolism and radiation dosimetry of 18F-tetrafluoroborate (18F-TFB) in healthy human subjects.

Science.gov (United States)

Jiang, Huailei; Schmit, Nicholas R; Koenen, Alex R; Bansal, Aditya; Pandey, Mukesh K; Glynn, Robert B; Kemp, Bradley J; Delaney, Kera L; Dispenzieri, Angela; Bakkum-Gamez, Jamie N; Peng, Kah-Whye; Russell, Stephen J; Gunderson, Tina M; Lowe, Val J; DeGrado, Timothy R

2017-10-27

18 F-Tetrafluoroborate ( 18 F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18 F-TFB in healthy human subjects. 18 F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18 F-TFB (333-407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. 18 F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18 F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18 F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18 F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18 F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). This initial study in healthy human subjects showed 18 F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18 F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide.

Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model

International Nuclear Information System (INIS)

Wang, H.-E.; Wu, S.-Y.; Chang, C.-W.; Liu, R.-S.; Hwang, L.-C.; Lee, T.-W.; Chen, J.-C.; Hwang, J.-J.

2005-01-01

2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two 18 F-labeled amino acid derivatives, O-2-[ 18 F]fluoroethyl-L-tyrosine (L-[ 18 F]FET) and 4-borono-2-[ 18 F]fluoro-L-phenylalanine-fructose (L-[ 18 F]FBPA-Fr), to that of [ 18 F]FDG in an animal brain tumor model. Methods: A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) L-[ 18 F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of L-[ 18 F]FET, L-[ 18 F]FBPA-Fr and [ 18 F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats. Results: The radiochemical purity of L-[ 18 F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of L-[ 18 F]FET and L-[ 18 F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [ 18 F]FDG kept increasing during the study period. The biodistribution of L-[ 18 F]FET, L-[ 18 F]FBPA-Fr and [ 18 F]FDG in the brain tumors was 1.26±0.22, 0.86±0.08 and 2.77±0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of L-[ 18 F]FET (3.15) and L-[ 18 F]FBPA-Fr (3.44) were higher than that of [ 18 F]FDG (1.44). Both microPET images and autoradiograms of L-[ 18 F]FET and L-[ 18 F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [ 18 F]FDG showed high uptake in the normal brain and gave blurred brain tumor images. Conclusion: Both L-[ 18 F]FET and L-[ 18 F]FBPA-Fr are superior to [ 18 F]FDG for the brain tumor imaging as shown in this study with microPET

Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-β-D-arabinofuranosylcytosine ([18F]FIAC)

International Nuclear Information System (INIS)

Wu, C.-Y.; Chan, P.-C.; Chang, W.-T.; Liu, R.-S.; Alauddin, Mian M.; Wang, H-E.

2009-01-01

We reported the synthesis of 2'-deoxy-2'-[ 18 F]fluoro-5-iodo-1-β-D-arabinofuranosyl-5-iodo-cytosine ([ 18 F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The 18 F-fluorosugar was converted to 1-bromo- 18 F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable β-anomer selectivity (α/β=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the β-[ 18 F]FIAC with high radiochemical purity (≥98%).

Analysis of gene expression profiles of hepatocellular carcinomas with regard to 18F-fluorodeoxyglucose uptake pattern on positron emission tomography

International Nuclear Information System (INIS)

Lee, Jong Doo; Yun, Mijin; Lee, Jae Myun; Choi, Youjeong; Choi, Youn-Hee; Kim, Ji Su; Kim, Se Jong; Park, Jeon Han; Kim, Kyung Sik; Lee, Woo Jung; Yang, Woo Ick; Park, Young Nyun; Han, Kwang-Hyub; Yoo, Naechun; Lim, Sang Moo

2004-01-01

18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumour aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of hepatocellular carcinomas (HCCs) were evaluated to determine whether HCCs with high 18 F-FDG uptake have more aggressive biological potential than those with low uptake. Surgical specimens were obtained from ten patients with HCC (six males and four females, age range 38-68 years). The tumour samples were divided into two groups based on the 18 F-FDG PET scan findings: high 18 F-FDG uptake (n=4) and low 18 F-FDG uptake (n=6). The pathological tumour grade was closely correlated with the 18 F-FDG uptake pattern: HCCs with high 18 F-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were either grade II or grade II with a focal area of grade III. The total RNA was extracted from the frozen tissues of all HCCs (n=10) and adjacent non-cancerous tissue (n=7). The gene expression profiles were evaluated using an oligoDNA microarray. The HCCs with high 18 F-FDG uptake showed increased expression of 11 genes - including vascular cell adhesion molecule-1, vinexin beta and core 1 UDP-galactose: N-acetylgalactosamine-alpha-R-beta 1,3-galactosyltransferase and the natural killer cell inhibitory receptor - compared to those with low uptake (p 18 F-FDG uptake appear to have more aggressive biological properties than those with low uptake. (orig.)

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

Science.gov (United States)

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

2014-02-01

Because the clinical course of low-grade gliomas in the individual adult patient varies considerably and is unpredictable, we investigated the prognostic value of dynamic (18)F-fluorethyltyrosine ((18)F-FET) PET in the early diagnosis of astrocytic low-grade glioma (World Health Organization grade II). Fifty-nine patients with newly diagnosed low-grade glioma and dynamic (18)F-FET PET before histopathologic assessment were retrospectively investigated. (18)F-FET PET analysis comprised a qualitative visual classification of lesions; assessment of the semiquantitative parameters maximal, mean, and total standardized uptake value as ratio to background and biologic tumor volume; and dynamic analysis of intratumoral (18)F-FET uptake over time (increasing vs. decreasing time-activity curves). The correlation between PET parameters and progression-free survival, overall survival, and time to malignant transformation was investigated. (18)F-FET uptake greater than the background level was found in 34 of 59 tumors. Dynamic (18)F-FET uptake analysis was available for 30 of these 34 patients. Increasing and decreasing time-activity curves were found in 18 and 12 patients, respectively. Neither the qualitative factor presence or absence of (18)F-FET uptake nor any of the semiquantitative uptake parameters significantly influenced clinical outcome. In contrast, decreasing time-activity curves in the kinetic analysis were highly prognostic for shorter progression-free survival and time to malignant transformation (P dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.

Chilean experience in production of 18F-FDG from 18F in a reactor

International Nuclear Information System (INIS)

Chandia, M.; Godoy, N.; Errazu, X.; Hernandez; Figols, M.; Firnau, G.; Tronsoco, F.

2000-01-01

18 F-FDG (fluorine-deoxy-D-glucose) is an important and useful radiopharmaceutical for imaging and study of myocardial viability. Usually cyclotron-produced 18 F is used to label 18 F-FDG. The availability of a 5 MW Nuclear Reactor in Chile and the absence of a quality cyclotron to produce 18 F required that we developed a method in order to obtain suitable 18 F to label 18 F-FDG using the facilities we have at the Nuclear Center of La Reina, Chilean Nuclear Energy Commission. The nuclear reactions involved are: 6 Li(n,aα) 3 H and 16 O( 3 H,n) 18 F. Enriched Li 2 CO 3 ( 6 Li = 95 %) was irradiated in a 5 MW swimming pool type nuclear reactor with a neutron flux of 5. 7 x 10 13 n cm -2 s -1 for 4 hours. The irradiated Li 2 CO 3 was dissolved in H 2 SO 4 (1:1) and distilled as trimethylsilyl( 18 F)fluoride ( 18 F-TMS). The labelling of the sugar was carried out using the method described by Hamacker. The 18 F-TMS was trapped in a solution of acetonitrile, water, potassium carbonate, and kriptofix and hydrolysed to form 18 F fluoride. The nucleophilic complex reacts with 1,3,4,6, tetra-O-acetyl- 2-O-trifluoromethanesulfonyl-bβ-D-mannopyranose. The acetylated carbohydrate by acid hydrolysis produces 18 F-FDG. The final product was purified using an ion retarding resin (AG11-A8) and a system two Sep Pak Plus: Alumina and C-18 cartridge and sterilised by Millipore 0.22 μm filter. The 18 F-FDG was obtained in an apyrogenic and sterile solution. The 18 F radionuclide purity was higher than 99.9% and the radiochemical purity ofthe 18 F-FDG obtained was over than 99%. Residual 3 H content was as low as 20 (Bq 3 H/MBq 18 F-FDG.). The yield of the process 18 F-FDG was 13.2 %. (authors)

Evaluation of TSPO PET Ligands [18F]VUIIS1009A and [18F]VUIIS1009B: Tracers for Cancer Imaging.

Science.gov (United States)

Tang, Dewei; Li, Jun; Buck, Jason R; Tantawy, Mohamed Noor; Xia, Yan; Harp, Joel M; Nickels, Michael L; Meiler, Jens; Manning, H Charles

2017-08-01

Positron emission tomography (PET) ligands targeting translocator protein (TSPO) are potential imaging diagnostics of cancer. In this study, we report two novel, high-affinity TSPO PET ligands that are 5,7 regioisomers, [ 18 F]VUIIS1009A ([ 18 F]3A) and [ 18 F]VUIIS1009B ([ 18 F]3B), and their initial in vitro and in vivo evaluation in healthy mice and glioma-bearing rats. VUIIS1009A/B was synthesized and confirmed by X-ray crystallography. Interactions between TSPO binding pocket and novel ligands were evaluated and compared with contemporary TSPO ligands using 2D 1 H- 15 N heteronuclear single quantum coherence (HSQC) spectroscopy. In vivo biodistribution of [ 18 F]VUIIS1009A and [ 18 F]VUIIS1009B was carried out in healthy mice with and without radioligand displacement. Dynamic PET imaging data were acquired simultaneously with [ 18 F]VUIIS1009A/B injections in glioma-bearing rats, with binding reversibility and specificity evaluated by radioligand displacement. In vivo radiometabolite analysis was performed using radio-TLC, and quantitative analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry. Both VUIIS1009A (3A) and VUIIS1009B (3B) were found to exhibit exceptional binding affinity to TSPO, with observed IC 50 values against PK11195 approximately 500-fold lower than DPA-714. However, HSQC NMR suggested that VUIIS1009A and VUIIS1009B share a common binding pocket within mammalian TSPO (mTSPO) as DPA-714 and to a lesser extent, PK11195. [ 18 F]VUIIS1009A ([ 18 F]3A) and [ 18 F]VUIIS1009B ([ 18 F]3B) exhibited similar biodistribution in healthy mice. In rats bearing C6 gliomas, both [ 18 F]VUIIS1009A and [ 18 F]VUIIS1009B exhibited greater binding potential (k 3 /k 4 )in tumor tissue compared to [ 18 F]DPA-714. Interestingly, [ 18 F]VUIIS1009B exhibited significantly greater tumor uptake (V T ) than [ 18 F]VUIIS1009A, which was attributed primarily to greater plasma

{sup 18}F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: A clinicopathological study

Energy Technology Data Exchange (ETDEWEB)

Kaira, Kyoichi, E-mail: kkaira1970@yahoo.co.jp [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Abe, Masato [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Takahashi, Toshiaki; Murakami, Haruyasu; Shukuya, Takehito; Kenmotsu, Hirotsugu; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Hayashi, Isamu [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Oriuchi, Noboru [Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Gunma (Japan); Endo, Masahiro [Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Kondo, Haruhiko [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakajima, Takashi [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan)

2012-09-15

Background: The usefulness of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of {sup 18}F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of {sup 18}F-FDG PET in primary mediastinal (non-thymic) neoplasms. Methods: Twenty-one patients with mediastinal neoplasms who underwent {sup 18}F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p-mTOR); cell cycle control (p53). Results: Seventeen of 21 patients were imaged on PET system using {sup 18}F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. {sup 18}F-FDG uptake was significantly correlated with Glut1, HIF-1α, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of {sup 18}F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. Conclusion: The amount of {sup 18}F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1α) and upstream components of HIF-1α (EGFR, p-Akt and p-S6K)

[{sup 18}F]FDG-PET in large vessel vasculitis; [{sup 18}F]FDG-PET bei Grossgefaess-Vaskulitiden

Energy Technology Data Exchange (ETDEWEB)

Hauser, A.S.D.; Walter, M.A. [Universitaetsspital Basel (Switzerland). Inst. fuer Nuklearmedizin

2007-06-15

[{sup 18}F]FDG-PET is a non-invasive metabolic imaging modality based on the regional distribution of fluorine-18-fluorodeoxyglucose that is highly effective in assessing the activity and the extent of giant cell arteritis and Takayasu's arteritis. It has shown to identify more affected vascular regions than morphologic imaging with Magnetic Resonance Imaging in both diseases. A visual grading of vascular [{sup 18}F]FDG-uptake helps to discriminate arteritis from atherosclerosis und therefore provides high specificity. High sensitivity is reached by scanning during the active inflammatory phase. [{sup 18}F]FDG-PET has the potential to develop into a valuable tool in the diagnostic work-up of giant cell arteritis and Takayasu's arteritis, respectively, and might become a first-line investigation technique. Therefore consensus regarding the most favorable imaging procedure as well as further clinical evidence is needed. The purpose of this review is to summarize current information on the present clinical data and to assist nuclear medicine practitioners in recommending, performing and interpreting the results of [{sup 18}F]FDG-PET in patients with suspected large vessel vasculitis. (orig.)

Synthesis of [18F]-5-fluorouridine (F-18-5-FUR) as a probe for measuring RNA synthesis and tumor growth rates in vivo

International Nuclear Information System (INIS)

Shiue, C.Y.; Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

1979-01-01

A method for the rapid synthesis of high specific activity of [ 18 F]-5-fluorouridine is described. The 20 Ne(d,α) 18 F nuclear reaction is used to produce high specific activity, anhydrous [ 18 F]-F 2 at the Brookhaven National Laboratory 60'' cyclotron. Fluorination of 2',3',5'-tri-0-acetyluridine with [ 18 F]-F 2 in glacial acetic acid at room temperature followed by hydrolysis with sodium methoxide in methanol gives [ 18 F]-5-fluorouridine with a radiochemical yield of 5 to 7% in a synthesis time of 90 minutes from EOB. The compound is required for the study of RNA synthesis and tumor growth rates in vivo

Validation of an HPLC method for determination of chemical purity of [18F]fluoromisonidazole ([18F]FMISO)

International Nuclear Information System (INIS)

Nascimento, Natalia C.E.S.; Oliveira, Mércia L.; Lima, Fernando R.A.; Silveira, Marina B.; Ferreira, Soraya Z.; Silva, Juliana B.

2017-01-01

[ 18 F]Fluoromisonidazole ([ 18 F]FMISO) is a nitroimidazole derivative labelled with fluorine-18 that selectively binds to hypoxic cells. It has been shown to be a suitable PET tracer for imaging hypoxia in tumors as well as in noncancerous tissues. [ 18 F]FMISO was prepared using a TRACERlabMX FDG ® module (GE) with cassettes, software sequence and reagents kits from ABX. In this work, we aimed to develop and to validate a new high performance liquid chromatography (HPLC) method for determination of chemical purity of [ 18 F]FMISO. Analyses were performed with an Agilent chromatograph equipped with radioactivity and UV detectors. [ 18 F]FMISO and impurities were separated on a C18 column by gradient elution with water and acetonitrile. Selectivity, linearity, detection limit (DL), quantification limit (LQ), precision, accuracy and robustness were assessed to demonstrate that the HPLC method is adequate for its intended purpose. The HPLC method showed a good precision, as all RSD values were lower than 5%. Robustness was evaluated considering a variation on parameters such mobile phase gradient and flow rate. Results evidenced that the HPLC method is validated and is suitable for radiochemical purity evaluation of [ 18 F]FMISO, considering operational conditions of our laboratory. As an extension of this work, other analytical methods used for [ 18 F]FMISO quality control should be evaluated, in compliance with good manufacture practice. (author)

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

Science.gov (United States)

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

2016-01-01

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

The rapid synthesis of high purity [{sup 18}F]butyrophenone neuroleptics from nitro precursors for PET study

Energy Technology Data Exchange (ETDEWEB)

Hashizume, Kazunari; Hashimoto, Naoto; Kato, Hiroo; Cork, D G; Miyake, Yoshihiro [National Cardiovascular Center, Suita, Osaka (Japan)

1995-04-01

We have completed rapid syntheses of [{sup 18}F]butyrophenone neuroleptics ([{sup 18}F]haloperidol and [{sup 18}F]spiperone) from their nitro precursors in high radiochemical yields (up to 21%) by combining a one-step nitro-fluoro exchange reaction and a novel high performance liquid chromatography (HPLC) separation method. The synthesis time was ca. 95 min and both the radiochemical and chemical purities of the labeled products were over 99%. (author).

18F fluorination using macrocyclic polyethers

International Nuclear Information System (INIS)

Klatte, B.; Knoechel, A.

The aim of this work is the nucleophilic substitution labelling with 18 F with high selectivity and yield for a short reaction time. Labelling with little or no carrier presumes that 18 F is obtained in anhydrons form. Starting with the production via the nuclear reaction 20 Ne(d,α) 18 F, the 18 F formed is to be continuously converted into an alkali polyether complex whose purpose is to increase the reactivity of the fluoride (compared to the non-complexed anion form), so that nucleophilic substitution reactions can be carried out faster and more carefully. A report is given on the working program and on first results to optimize the carrier-poor synthesis with polyethers as synthesis agent. (RB) [de

PET/CT studies of multiple myeloma using {sup 18}F-FDG and {sup 18}F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Goldschmidt, Hartmut; Hose, Dirk [University of Heidelberg, Medical Clinic V, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany); Pan, Leyun; Cheng, Caixia; Dimitrakopoulou-Strauss, Antonia [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

2014-07-15

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) and fluorine-18 sodium fluoride ({sup 18}F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions. The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased {sup 18}F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the {sup 18}F-NaF PET/CT scans were then correlated with those detected on {sup 18}F-FDG PET/CT, which served as a reference. Moreover, the {sup 18}F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach. Whole body {sup 18}F-FDG PET/CT revealed approximately 343 focal lesions while {sup 18}F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in {sup 18}F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with {sup 18}F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal {sup 18}F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with {sup 18}F-NaF PET/CT. In three patients with multiple focal {sup 18}F-FDG-uptake, {sup 18}F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with {sup 18}F-FDG and {sup 18}F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of {sup 18}F-FDG revealed the

Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

International Nuclear Information System (INIS)

Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N.; Wiebe, Leonard I.

2009-01-01

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[ 18 F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18 F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18 F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18 F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18 F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18 F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18 F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18 F-FAZA were observed. This study suggests that 18 F-FAZA may be a very useful radiopharmaceutical

Vasculitis assessment with [18F]F.D.G. positron emission tomography

International Nuclear Information System (INIS)

Liozon, E.; Monteil, J.

2008-01-01

[ 18 F]fluorodeoxyglucose ( 18 F.D.G.) positron emission tomography (PET) is a noninvasive metabolic imaging modality that is well suited to the assessment of activity and extent of large vessel vasculitis, such as giant cell arteritis and Takayasu arteritis. PET could be more effective than magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. The visual grading of vascular [ 18 F]F.D.G. uptake makes it possible to discriminate arteritis from atherosclerosis, providing therefore high specificity. High sensitivity can be achieved provided scanning is performed during active inflammatory phase, preferably before starting corticosteroid treatment. Large scale prospective studies are needed to determine the exact value of PET imaging in assessing the large vessel vasculitis outcome and response to immunosuppressive treatment

Imaging malignant melanoma with {sup 18}F-5-FPN

Energy Technology Data Exchange (ETDEWEB)

Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

2016-01-15

Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

[{sup 18}F]FDG PET/CT outperforms [{sup 18}F]FDG PET/MRI in differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Vrachimis, Alexis; Wenning, Christian; Weckesser, Matthias; Stegger, Lars [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Burg, Matthias Christian; Allkemper, Thomas [University Hospital Muenster, Department of Clinical Radiology, Muenster (Germany); Schaefers, Michael [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Westfaelische Wilhelms University Muenster, European Institute for Molecular Imaging, Muenster (Germany)

2016-02-15

To evaluate the diagnostic potential of PET/MRI with [{sup 18}F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [{sup 18}F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [{sup 18}F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [{sup 18}F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. In patients with thyroid cancer and suspected or known dedifferentiation, [{sup 18}F]FDG PET/MRI was inferior to low-dose [{sup 18}F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [{sup 18}F]FDG PET/MRI was equal to contrast-enhanced neck [{sup 18}F]FDG PET/CT. Therefore, [{sup 18}F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast

Stability and the improved methods of "1"8F-FDG

International Nuclear Information System (INIS)

Zhang Jinming; Li Yungang; Liu Jian; Zhang Xiaojun; Tian Jiahe

2011-01-01

To study the stability of "1"8F-FDG with routinely synthesis at high radio-dose and high radioconcentration, "1"8F-FDG was added 0.1% ethanol or repurification by solid-phase extract ion for radiolytic "1"8F-FDG to improve its radiochemical purity (RCP). The results showed that the RCP declined from 99% to 95% within 4 h at 6 TBq/L for room temperature (RT). The radiolysis could be depressed with 0.1% ethanol, the RCP could be over 95% even if the radioactivity concentration was 7.4 TBq/L at RT for 6 h. The repurification method could improve the RCP of "1"8F-FDG from 80% to 99%. Micro PET/ CT imagings of normal rats showed that the vertebra had high uptake with radiolytic "1"8F-FDG because of impurity. There were no radioactivity uptaking in bone with repuification of "1"8F- FDG. It indicated that 0.1% ethanol could be used as stabilizers for "1"8F-FDG to improve the RCP when "1"8F-FDG had high radio-do se and high radioconcentrtion. The radiolytic 18 F-FDG could be repurified by so lid-phase extraction to remove the radio-impurity. The method of added 0.1% thanot could be combined with repurification method to assure the RCP of "1"8F-FDG for over 95% at any given time andradiodose or contcentrayion. (authors)

Carrier-added and no-carrier-added syntheses of [18F]spiroperidol and [18F]haloperidol

International Nuclear Information System (INIS)

Kilbourn, M.R.; Welch, M.J.; Dence, C.S.; Tewson, T.J.; Saji, H.; Maeda, M.

1984-01-01

Syntheses of [ 18 F]haloperidol and [ 18 F]spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added [ 18 F]butyrophenone neuroleptics were prepared in low ( 18 F-neuroleptics were prepared in better (5-17%) yields by 18 F-for- 19 F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described. (author)

Biodistribution and PET imaging of [18F]-fluoroadenosine derivatives

International Nuclear Information System (INIS)

Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

2007-01-01

Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[ 18 F]fluoro-1-β-D-arabinofuranosyl-adenine ([ 18 F]-FAA) and 3'-deoxy-3'-[ 18 F]fluoro-1-β-D-xylofuranosyl-adenine ([ 18 F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [ 18 F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [ 18 F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [ 18 F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [ 18 F]FAA in spleen and visualization of tumors, and high uptake of [ 18 F]FXA in the heart. Conclusion: These results suggest that [ 18 F]FAA may be useful for tumor imaging, while [ 18 F]FXA may have potential as a heart imaging agent with PET

Full Automatic synthesis of [18F]FMISO

International Nuclear Information System (INIS)

Seung Jun Oh; Se Hun Kang; Jin-Sook Ryu; Dae Hyuk Moon

2004-01-01

[ 18 F]FMISO is a radiopharmaceutical for hypoxia imaging. Although it was developed in 1986, there has been no report about automatic synthesis. In this experiment, we established the full automatic synthesis of [ 18 F]FMISO and evaluate the stability according to ICH guideline. Method: We used GE MicroLab MX for automatic synthesis. Sequence program was modified to control of the module as follows: [ 18 F]Fluoride drying→[ 18 F]fluorination→trapping of reaction mixture on C18 cartridge→purification-elution of reaction mixture→hydrolysis and HPLC purification. We used disposable cassette for each synthesis and discard it after synthesis. To find optimal synthesis condition, we tested 90 120 degree C as reaction temperature, 5 15 mg of 1-(2-nitro-1-imidazolyl) -2-O-tetrahtdropyranyl-3-O-toluenesulfonyl-propanediol as precursor and 5 15 min as [ 18 F]fluorination time. HPLC purification condition was EtOH:H20 = 5:95, 5ml/min with Alltech Econosil column. To check the stability of production, we performed 30 times of run. We checked the radiochemical stability until 6 hours at 25 degree C and 40% humidity condition. We also performed the stability test at 50 70 degree C with 60-80% humidity condition or under UV light for 6 hours after synthesis for acceleration test, Results: The optimal [ 18 F] fluorination condition was 10mg of precursor and 15 min incubation at 110 degree C. Hydrolysis was performed at 105 degree C for 5 min. After HPLC purification, radiochemical yields and purity were 45±2.8 and 98±1.2%, respectively. Total synthesis time was 60±5.2 min. [ 18 F]FMISO was stable until 6 hours after production with 97±2.4% of radiochemical purity. [ 18 F]FMISO was also stable in acceleration test and photochemical test with 97±2.4 and 97±2.8% of radiochemical purity, respectively. Conclusion: We established the full automatic synthesis method of [ 18 F]FMISO with reproducible high production yield. [18F]FMISO synthesized by this method was stable

Radiosynthesis and biological evaluation of an {sup 18}F-labeled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon

Energy Technology Data Exchange (ETDEWEB)

Hoepping, Alexander [ABX Advanced Biochemical Compounds GmbH, 01454 Radeberg (Germany); Scheunemann, Matthias [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany); Fischer, Steffen [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany); Deuther-Conrad, Winnie [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany); Hiller, Achim [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany); Wegner, Florian [Department of Neurology, University of Leipzig, 04103 Leipzig (Germany); Diekers, Michael [ABX Advanced Biochemical Compounds GmbH, 01454 Radeberg (Germany); Steinbach, Joerg [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany); Brust, Peter [Institute of Interdisciplinary Isotope Research, 04318 Leipzig (Germany)]. E-mail: brust@iif-leipzig.de

2007-07-15

Introduction: Gamma amino butyric acid type A (GABA{sub A}) receptors are involved in a variety of neurological and psychiatric diseases, which have promoted the development and use of radiotracers for positron emission tomography imaging. Radiolabeled benzodiazepine antagonists such as flumazenil have most extensively been used for this purpose so far. Recently, the non-benzodiazepine pyrazolopyrimidine derivative indiplon with higher specificity for the {alpha}{sub 1} subtype of the GABA{sub A} receptor has been introduced for treatment of insomnia. The aim of this study was the development and biological evaluation of an {sup 18}F-labeled derivative of indiplon. Methods: Both [{sup 18}F]fluoro-indiplon and its labeling precursor were synthesized by two-step procedures starting from indiplon. The radiosynthesis of [{sup 18}F]fluoro-indiplon was performed using the bromoacetyl precursor followed by multiple-stage purification using semipreparative HPLC and solid phase extraction. Stability, partition coefficients, binding affinities and regional brain binding were determined in vitro. Biodistribution and radiotracer metabolism were studied in vivo. Results: [{sup 18}F]Fluoro-indiplon was readily accessible in good yields (38-43%), with high purity and high specific radioactivity (>150 GBq/{mu}mol). It displays high in vitro stability and moderate lipophilicity. [{sup 18}F]Fluoro-indiplon has an affinity to GABA{sub A} receptors comparable to indiplon (K {sub i}=8.0 nM vs. 3.4 nM). In vitro autoradiography indicates high [{sup 18}F]fluoro-indiplon binding in regions with high densities of GABA{sub A} receptors. However, ex vivo autoradiography and organ distribution studies show no evidence of specific binding of [{sup 18}F]fluoro-indiplon. Furthermore, the radiotracer is rapidly metabolized with high accumulation of labeled metabolites in the brain. Conclusions: Although [{sup 18}F]fluoro-indiplon shows good in vitro features, it is not suitable for in vivo

PET imaging with [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) following selective lesion of cholinergic pedunculopontine tegmental neurons in rat

International Nuclear Information System (INIS)

Cyr, Marilyn; Parent, Maxime J.; Mechawar, Naguib; Rosa-Neto, Pedro; Soucy, Jean-Paul; Aliaga, Antonio; Kostikov, Alexey; Maclaren, Duncan A.A.; Clark, Stewart D.; Bedard, Marc-Andre

2014-01-01

Introduction: [ 18 F]fluoroethoxybenzovesamicol ([ 18 F]FEOBV) is a PET radiotracer with high selectivity and specificity to the vesicular acetylcholine transporter (VAChT). It has been shown to be a sensitive in vivo measurement of changes of cholinergic innervation densities following lesion of the nucleus basalis of Meynert (NBM) in rat. The current study used [ 18 F]FEOBV with PET imaging to detect the effect of a highly selective lesion of the pedunculopontine (PPTg) nucleus in rat. Methods: After bilateral and selective lesions of the PPTg cholinergic neurons, rats were scanned using [ 18 F]FEOBV, then sacrificed, and their brain tissues collected for immunostaining and quantification of the VAChT. Results: Comparisons with control rats revealed that cholinergic losses can be detected in the brainstem, lateral thalamus, and pallidum by using both in vivo imaging methods with [ 18 F]FEOBV, and ex vivo measurements. In the brainstem PPTg area, significant correlations were observed between in vivo and ex vivo measurements, while this was not the case in the thalamic and pallidal projection sites. Conclusions: These findings support PET imaging with [ 18 F]FEOBV as a reliable in vivo method for the detection of neuronal terminal losses resulting from lesion of the PPTg. Useful applications can be found in the study of neurodegenerative diseases in human, such as Parkinson’s disease, multiple system atrophy, progressive supranuclear palsy, or dementia with Lewy bodies

Staging and Functional Characterization of Pheochromocytoma and Paraganglioma by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography

Science.gov (United States)

Timmers, Henri J. L. M.; Chen, Clara C.; Carrasquillo, Jorge A.; Whatley, Millie; Ling, Alexander; Eisenhofer, Graeme; King, Kathryn S.; Rao, Jyotsna U.; Wesley, Robert A.; Adams, Karen T.

2012-01-01

F-FDG = 93.7%; of CT/MRI = 76.7%; difference = 17.0%, 95% CI = 4.9% to 28.5%, P = .013). Conclusions Compared with 123I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by 18F-FDG PET. 18F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL. PMID:22517990

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

Science.gov (United States)

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

2014-03-01

/MR imaging exhibited a high correlation (R = 0.74 and 0.86, respectively; P dedicated pulmonary MR imaging protocol, compared with (18)F-FDG PET/CT, does not provide advantages in thoracic staging in NSCLC patients.

Radiation exposure of radiographers who handle 18 F ...

African Journals Online (AJOL)

18F-fluorodeoxyglucose (18F-FDG) is used in most diagnostic applications of Positron Emission Tomography (PET). It has high annihilation energy of 511 keV, which results in potentially high radiation doses for staff. This study investigated radiographer radiation exposure during receipt, administration and scanning of ...

F-18 Radiopharmaceuticals

International Nuclear Information System (INIS)

2001-12-01

This document includes 8 presentations delivered at the symposium. The topics discussed include: optimization of accelerator production of 18 F- and 18 F 2 -fluorodeoxyglucose; radiopharmaceuticals synthesis, synthesis modules, pharmacopoeia and GLP; quality control; radiation safety of production and application; PET imaging in human medicine. Each presentation has been indexed separately

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

DEFF Research Database (Denmark)

Jensen, Mette Munk; Kjaer, Andreas

2015-01-01

treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can......Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response...

Automatic synthesis of 16α-[18F]fluoro-17β-estradiol using a cassette-type [18F]fluorodeoxyglucose synthesizer

International Nuclear Information System (INIS)

Mori, Tetsuya; Kasamatsu, Shingo; Mosdzianowski, Christoph; Welch, Michael J.; Yonekura, Yoshiharu; Fujibayashi, Yasuhisa

2006-01-01

16α-[ 18 F]fluoro-17β-estradiol ([ 18 F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [ 18 F]FES by modifying a cassette-type [ 18 F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 o C for 10 min with dried [ 18 F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 o C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO 3 , and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-μm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [ 18 F]FES was synthesized with a yield of 76.4±1.9% (n=5). The yield as the final product for clinical use was 42.4±3.2% (n=5, decay corrected). The total preparation time was 88.2±6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/μmol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [ 18 F]FES safe for clinical use with high and reproducible yield

Biological distribution of [18F-FDG] using reactor produced [18F

International Nuclear Information System (INIS)

Sierralta, P.; Massardo, T; Gil, M.C; Gonzalez, P; Chandia, M.; Godoy, N.; Troncoso, F

2002-01-01

The animal model that relates biodistribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after a recent MI, the use of reactor produced [ 18 F]-FDG (a radiotracer usually obtained in Cyclotron) is proposed, production of which has never been attempted in our country. Specific Activities founded in the different tissues after injection of this radiotracer in an animal model were compared with those obtained by other authors with cyclotron [ 18 F]-FDG. No statistically significant differences in the critical organs were found. Hence, reactor produced [ 18 F]-FDG is a useful radiopharmaceutical in cardiac cellular metabolism assessment (author)

Utility of {sup 18}F-fluoroestradiol ({sup 18}F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Energy Technology Data Exchange (ETDEWEB)

Lin, Frank I. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Gonzalez, E.M.; Kurdziel, K.A.; Ton, A.; Turkbey, B.; Choyke, P.L.; Lindenberg, M.L. [National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Kummar, S.; Do, K.; Collins, J.M.; Doroshow, J.H. [National Cancer Institute, Division of Cancer Treatment and Diagnosis and Center for Cancer Research, Bethesda, MD (United States); Shih, J. [National Cancer Institute, NIH, Biometric Research Program, Bethesda, MD (United States); Adler, S. [Leidos Biomedical Research, Inc., Clinical Research Directorate/Clinical Monitoring Research Program, Frederick, MD (United States); Jacobs, P.M. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); Bhattacharyya, S. [Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States); Chen, A.P. [National Cancer Institute, Early Clinical Trials Development Program, DCTD, Bethesda, MD (United States)

2017-03-15

Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. {sup 18}F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes {sup 18}F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with {sup 18}F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with {sup 18}F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy. (orig.)

[18F]FDG-PET in large vessel vasculitis

International Nuclear Information System (INIS)

Hauser, A.S.D.; Walter, M.A.

2007-01-01

[ 18 F]FDG-PET is a non-invasive metabolic imaging modality based on the regional distribution of fluorine-18-fluorodeoxyglucose that is highly effective in assessing the activity and the extent of giant cell arteritis and Takayasu's arteritis. It has shown to identify more affected vascular regions than morphologic imaging with Magnetic Resonance Imaging in both diseases. A visual grading of vascular [ 18 F]FDG-uptake helps to discriminate arteritis from atherosclerosis und therefore provides high specificity. High sensitivity is reached by scanning during the active inflammatory phase. [ 18 F]FDG-PET has the potential to develop into a valuable tool in the diagnostic work-up of giant cell arteritis and Takayasu's arteritis, respectively, and might become a first-line investigation technique. Therefore consensus regarding the most favorable imaging procedure as well as further clinical evidence is needed. The purpose of this review is to summarize current information on the present clinical data and to assist nuclear medicine practitioners in recommending, performing and interpreting the results of [ 18 F]FDG-PET in patients with suspected large vessel vasculitis. (orig.)

Recoil 18F chemistry. XI. High pressure investigation of 1,1-difluoroethane

International Nuclear Information System (INIS)

Manning, R.G.; Root, J.W.

1980-01-01

Nuclear recoil 18 F reactions in CH 3 CHF 2 have been investigated throughout the effective pressure range 0.3--190 atm. The principal reaction channel is F-to-HF abstraction for which the combined yield from quasithermal and energetic processes in the presence of 5 mole% H 2 S additive is 83.4% +- 0.2%. A reaction mechanism is proposed that involves the organic product forming channels F-for-F, F-for-αH, F-for-βH, F-for-CH 3 and F-for-CHF 2 . The results are compared with those reported for the 18 F+CH 3 CF 3 system

High-Alpha Research Vehicle (HARV) longitudinal controller: Design, analyses, and simulation resultss

Science.gov (United States)

Ostroff, Aaron J.; Hoffler, Keith D.; Proffitt, Melissa S.; Brown, Philip W.; Phillips, Michael R.; Rivers, Robert A.; Messina, Michael D.; Carzoo, Susan W.; Bacon, Barton J.; Foster, John F.

1994-01-01

This paper describes the design, analysis, and nonlinear simulation results (batch and piloted) for a longitudinal controller which is scheduled to be flight-tested on the High-Alpha Research Vehicle (HARV). The HARV is an F-18 airplane modified for and equipped with multi-axis thrust vectoring. The paper includes a description of the facilities, a detailed review of the feedback controller design, linear analysis results of the feedback controller, a description of the feed-forward controller design, nonlinear batch simulation results, and piloted simulation results. Batch simulation results include maximum pitch stick agility responses, angle of attack alpha captures, and alpha regulation for full lateral stick rolls at several alpha's. Piloted simulation results include task descriptions for several types of maneuvers, task guidelines, the corresponding Cooper-Harper ratings from three test pilots, and some pilot comments. The ratings show that desirable criteria are achieved for almost all of the piloted simulation tasks.

Validation of an HPLC method for determination of chemical purity of [{sup 18}F]fluoromisonidazole ([{sup 18}F]FMISO)

Energy Technology Data Exchange (ETDEWEB)

Nascimento, Natalia C.E.S.; Oliveira, Mércia L.; Lima, Fernando R.A., E-mail: nataliafleming@hotmail.com, E-mail: mercial@cnen.gov.br, E-mail: falima@cnen.gov.br [Centro Regional de Ciências Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Silveira, Marina B.; Ferreira, Soraya Z.; Silva, Juliana B., E-mail: mbs@cdtn.br, E-mail: zandims@cdtn.br, E-mail: silvajb@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

[{sup 18}F]Fluoromisonidazole ([{sup 18}F]FMISO) is a nitroimidazole derivative labelled with fluorine-18 that selectively binds to hypoxic cells. It has been shown to be a suitable PET tracer for imaging hypoxia in tumors as well as in noncancerous tissues. [{sup 18}F]FMISO was prepared using a TRACERlabMX{sub FDG}® module (GE) with cassettes, software sequence and reagents kits from ABX. In this work, we aimed to develop and to validate a new high performance liquid chromatography (HPLC) method for determination of chemical purity of [{sup 18}F]FMISO. Analyses were performed with an Agilent chromatograph equipped with radioactivity and UV detectors. [{sup 18}F]FMISO and impurities were separated on a C18 column by gradient elution with water and acetonitrile. Selectivity, linearity, detection limit (DL), quantification limit (LQ), precision, accuracy and robustness were assessed to demonstrate that the HPLC method is adequate for its intended purpose. The HPLC method showed a good precision, as all RSD values were lower than 5%. Robustness was evaluated considering a variation on parameters such mobile phase gradient and flow rate. Results evidenced that the HPLC method is validated and is suitable for radiochemical purity evaluation of [{sup 18}F]FMISO, considering operational conditions of our laboratory. As an extension of this work, other analytical methods used for [{sup 18}F]FMISO quality control should be evaluated, in compliance with good manufacture practice. (author)

Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

2009-01-01

CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

High specific radioactivity (1R,2S)-4-[18F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

International Nuclear Information System (INIS)

Langer, Oliver; Valette, Heric; Dolle, Frederic; Halldin, Christer; Loc'h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-01-01

The radiolabeled catecholamine analogue (1R,2S)-6-[ 18 F]fluorometaraminol (6-[ 18 F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[ 18 F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[ 18 F]fluorometaraminol (4-[ 18 F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/μmol). In the present study, we demonstrate in rats that 4-[ 18 F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[ 18 F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[ 18 F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[ 18 F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[ 18 F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[ 18 F]FMR is a promising alternative to 6-[ 18 F]FMR for myocardial neuronal mapping with PET in humans

Synthetic improvement and animal experiment of 6-18F-DOPA

International Nuclear Information System (INIS)

Tang Ganghua; Tang Xiaolan; Wang Mingfang; Luo Lei; Li Zhi; Huang Zuhan; Zhang Lan; Wang Yongxian

2002-01-01

Objective: To study synthetic improvement and biodistribution of 6- 18 F-DOPA in normal rats and hemi-Parkinsonism rats. Methods: 6- 18 F-DOPA was synthesized from the starting material 6-nitropiperonal via multi-step reaction including the nucleophilic fluorination, reductive iodination with diiodosilane on Sep-Pak column, chiral catalytic phase-transfer alkylation, and hydrolysis reaction. Biodistribution of 6- 18 F-DOPA in normal rats and the brain of hemi-Parkinsonism rats was determined. Results: The total time of synthesis was less than 110 min, the total uncorrected radiochemical yield from potassium 6- 18 F-DOPA was 5%-18%, and the enantiomeric purity and radiochemical purity were above 97% and 98%, respectively. High uptake in the kidney, blood, striatum, and hippocampus, rapid blood clearance in the kidney and blood, long retaining time and high striatum/cerebellum and striatum/cortex 6- 18 F-DOPA uptake ratio were found in normal rats. Compared with the intact side of hemi-Parkinsonism rats and pseudo-operated group, 6- 18 F-DOPA uptake and striatum/cerebellum and striatum/cortex 6- 18 F-DOPA uptake ratio reduced significantly in the lesioned side of hemi-Parkinsonism rats (P 18 F-DOPA. The synthetic 6- 18 F-DOPA is allowed to be used to study the animal and Parkinson's disease with PET imaging

18F-labelling of oligonucleotides using succinimido 4-[18F]fluorobenzoat

International Nuclear Information System (INIS)

Hedberg, Elisabeth; Laangstroem, Bengt

1998-01-01

A general method for the labelling of oligodeoxynucleotide and oligonucleoside phosphorothioates in the 5'-position with the positron-emitting radionuclide 18 F (t 1/2 = 110 min) is described. The label was incorporated by the reaction of succinimido 4 -[ 18 F]fluorobenzoate 4 with oligonucleotides (18- and 20-mers) modified in the 5'-position with a hexylamine linker. Oligodeoxynucleotides 5'-GCT,AAG,CGA,TGC,CTC,CGT-3' (MTCa) and 5'-GAA,CCT,CTG,AGA,GTT,CAT,CT-3' (CROa) were labelled in 20±3 % (MTCa) and 13±3 % (CROa) radiochemical yields (non-isolated, decay-corrected and based on 4). Oligonucleoside phosphorotioates MTCa (S-MTCa) and CROa (S-CROa) were labelled in 9 and 7% isolated radiochemical yield, respectively (decay-corrected and based on 4). Labelled oligonucleotides and phosphorothioate analogues were separated from their unlabelled counterparts using reversed-phase perfusion chromatography. The molecular mass of a labelled oligonucleotide CROa was determined by ESI-MS after a mixed 18 F/ 19 F fluorobenzoate labelling experiment and corresponded with the expected structure. (au)

Breakout from the hot CNO cycle: the {sup 15}O({alpha},{gamma}) and {sup 18}Ne({alpha},p) reactions

Energy Technology Data Exchange (ETDEWEB)

Bradfield-Smith, W; Laird, A M; Davinson, T; Pietro, A di; Ostrowski, A N; Shotter, A C; Woods, P J [Dept. of Physics and Astronomy, Univ. of Edinburgh (United Kingdom); Cherubini, S; Galster, W; Graulich, J S; Leleux, P; Michel, L; Ninane, A; Vervier, J [Inst. de Physique Nucleaire, UCL, Louvain-la-Neuve (Belgium); Aliotta, M; Cali, D; Cappussello, F; Cunsolo, A; Spitaleri, C [INFN, Catania (Italy); Gorres, J; Wiescher, M [Notre Dame Univ. (United States); Rahighi, J [Van de Graaf Lab., Tehran (Iran, Islamic Republic of); Hinnefeld, J [Indiana Univ., South Bend (United States)

1998-06-01

One of the most important reactions which determines the rate of breakout from the hot CNO cycle is the {sup 15}O({alpha},{gamma}){sup 19}Ne. The reaction {sup 18}Ne({alpha},p){sup 21}Na may also provide an alternative breakout route. Experiments are being undertaken at Louvain-La-Neuve using the radioactive {sup 18}Ne beam to study these reactions by measurement of {alpha}({sup 18}Ne,p){sup 21}Na and d({sup 18}Ne,p){sup 19}Ne{sup *} {yields} {sup 15}O + {alpha} (orig.)

PET imaging of α{sub 7} nicotinic acetylcholine receptors: a comparative study of [{sup 18}F]ASEM and [{sup 18}F]DBT-10 in nonhuman primates, and further evaluation of [{sup 18}F]ASEM in humans

Energy Technology Data Exchange (ETDEWEB)

Hillmer, Ansel T.; Li, Songye; Zheng, Ming-Qiang; Lin, Shu-fei; Nabulsi, Nabeel; Holden, Daniel; Pracitto, Richard; Labaree, David; Ropchan, Jim; Esterlis, Irina; Cosgrove, Kelly P.; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, New Haven, CT (United States); Scheunemann, Matthias; Teodoro, Rodrigo; Deuther-Conrad, Winnie; Brust, Peter [Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Leipzig (Germany)

2017-06-15

The α{sub 7} nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α{sub 7} nAChRs PET radioligands, [{sup 18}F]ASEM 3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([{sup 18}F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [{sup 18}F]DBT-10 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([{sup 18}F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [{sup 18}F]ASEM in humans. PET scans with high specific activity [{sup 18}F]ASEM or [{sup 18}F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [{sup 18}F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [{sup 18}F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [{sup 18}F]ASEM distribution volume (V{sub T}). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V{sub T} was assessed. In the rhesus monkey brain [{sup 18}F]ASEM and [{sup 18}F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [{sup 18}F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [{sup 18}F]ASEM V{sub T}. [{sup 18}F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [{sup 18}F]ASEM V{sub T} in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V{sub T} values ranging from 19.6 ± 2

Biological distribution of [{sup 18}F-FDG] using reactor produced [{sup 18}F]; Distribucion biologica del {sup 18}F-Fluordeoxiglucosa utilizando [{sup 18}F] producido en reactor

Energy Technology Data Exchange (ETDEWEB)

Sierralta, P; Massardo, T [Centro de Medicina Nuclear. Hospital Clinico Universidad de Chile, Santiago (Chile); Gil, M C [CGM Nuclear, Santiago (Chile); Gonzalez, P [Centro de Medicina Nuclear. Hospital Clinico Universidad de Chile, Santiago (Chile); Chandia, M; Godoy, N; Troncoso, F [Comision Chilena de Energia Nuclear, Cen La Reina, Santiago (Chile)

2002-12-01

The animal model that relates biodistribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after a recent MI, the use of reactor produced [{sup 18}F]-FDG (a radiotracer usually obtained in Cyclotron) is proposed, production of which has never been attempted in our country. Specific Activities founded in the different tissues after injection of this radiotracer in an animal model were compared with those obtained by other authors with cyclotron [{sup 18}F]-FDG. No statistically significant differences in the critical organs were found. Hence, reactor produced [{sup 18}F]-FDG is a useful radiopharmaceutical in cardiac cellular metabolism assessment (author)

Efficient automated synthesis of 2-(5-["1"8F]fluoropentyl)-2-methylmalonic acid (["1"8F]ML-10) on a commercial available ["1"8F]FDG synthesis module

International Nuclear Information System (INIS)

Liu, Shaoyu; Nie, Dahong; Jiang, Shende; Tang, Ganghua

2017-01-01

["1"8F]ML-10 (2-(5-["1"8F]fluoro-pentyl)-2-methylmalonic acid) is a small molecule positron emission tomography (PET) probe for apoptosis imaging. Automated synthesis of ["1"8F]ML-10 was developed by using two different purification methods through a direct saponification procedure on a modified commercial ["1"8F]Fluoro-2-Deoxyglucose (["1"8F]FDG) synthesizer. C18 purification method 1: The final ["1"8F]ML-10 solution containing ethanol was obtained with radiochemical yields of 60±5% (n=5) at the end of bombardment (EOB) and radiochemical purity of 98% in 35 min. Al_2O_3 and SCX purification method 2: To avoid possible side effects of a conventional ethanol-containing formulation, an new ethanol-free solution of ["1"8F]ML-10 was also developed, the radiochemical yields was 50±5% (n=5, EOB) within 45 min and the radiochemical purity was 98%. - Highlights: • The production of ["1"8F]ML-10 was optimized by using a straightforward saponification procedure. • Automated synthesis was performed on a commonly FDG synthesis module. • An ethanol-containing ["1"8F]ML-10 formulation was obtained with high radiochemical yield in a shorter time. • An ethanol-free formulation method of ["1"8F]ML-10 was also developed.

An increased 18F radionuclide production

International Nuclear Information System (INIS)

Panico, M.; Salvadore, M.; Randazzo, G.; Roma, R.; Green, A.; Calicchio, G.F.

1999-01-01

In the 18 F daily preparation a diminished yield of radioisotopic production is often found. This fact, most times, is connected to the altered internal surface of the PEE and teflon lines for the 18 F transferring to the hot cells because of radiations. This anomaly is due to an H 2 18 O insufficient filling into the target. In fact a target foils bombardment causing the release of radioactive Ag+ ions sets in. These ions passing through the transferring line damage it. This problem has been solved by an increased H 2 18 O filling, from 0.7 to 1.3 mL. A further steady increasing in the 18 F production is due to the features of the new target: back plane : integrated in the silver flange; water cooling surface: enlarged with fins; target connections: high pressure fittings. In conclusion a careful filling of the new target has increased the fluorine-18 average daily production from 7.4 GBq to 18.5 GBq, using recovered water (time: thirty minutes; beam: 15 mA) and allows to replace teflon lines every year instead of every three months. (authors)

Pilot Preclinical and Clinical Evaluation of (4S-4-(3-[18F]Fluoropropyl-L-Glutamate (18F-FSPG for PET/CT Imaging of Intracranial Malignancies.

Directory of Open Access Journals (Sweden)

Erik S Mittra

Full Text Available (S-4-(3-[18F]Fluoropropyl-L-glutamic acid (18F-FSPG is a novel radiopharmaceutical for Positron Emission Tomography (PET imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years. After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7. 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.ClinicalTrials.gov NCT

Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG

International Nuclear Information System (INIS)

Belloli, Sara; Brioschi, Andrea; Politi, Letterio Salvatore; Ronchetti, Francesca; Calderoni, Sara; Raccagni, Isabella; Pagani, Antonella; Monterisi, Cristina; Zenga, Francesco; Zara, Gianpaolo; Fazio, Ferruccio; Mauro, Alessandro

2013-01-01

Introduction: The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods: Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [ 18 F]FDG- and [ 18 F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results: Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [ 18 F]FAZA and high-glucose metabolism regions recognized with [ 18 F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [ 18 F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [ 18 F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy. Conclusions: In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression

F-18 labelling agents

International Nuclear Information System (INIS)

Mikecz, P.

2001-01-01

In this presentation the production of fluorine-18, separation of [ 18 F]fluoride, converting fluoride into fluorine as well as fluorine incorporation into organic molecules are reviewed. Reaction schemes and technology schemes are included. Towards organic reactions, with help of small molecules of the 18 F can be introduced into a wide variety of radiopharmaceuticals. (author)

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

Science.gov (United States)

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

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sub 18/F)haloperidol

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M

1984-07-01

Syntheses of (18F)haloperidol and (18F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (18F)butyrophenone neuroleptics were prepared in low (less than 2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added 18F-neuroleptics were prepared in better (5-17%) yields by 18F-for-19F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

International Nuclear Information System (INIS)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N.; Karges, Wolfram; Pauls, Sandra; Verburg, Frederik A.; Dralle, Henning; Neumaier, Bernd; Mottaghy, Felix M.

2010-01-01

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18 F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. 18 F-DOPA PET, CT and 18 F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18 F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. 18 F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18 F-DOPA PET or CT alone. (orig.)

18F in hot atom chemistry and equilibrium chemical kinetics

International Nuclear Information System (INIS)

Root, J.W.; Tomiyoshi, Katsumi; Knickelbein, M.B.

1993-01-01

Superexcited molecules are unusual species that at present can only be investigated using nuclear recoil methods. The thermochemical technique for measuring the excitation energy distributions of superexcited molecules is reviewed and applied to recent studies of CF 3 18 F and C 2 F 5 18 F formed from high energy atomic exchange reactions in CF 4 and C 2 F 6 . The nascent CF 3 18 F and C 2 F 5 18 F range in energy from 1.7 to about 45 eV. The average energies of these products range from 15 to 20 eV. The internal excitation that accompanies these reactions is initially localized near the 18 F bonding site, and the C 2 F 5 18 F decomposition mechanism is non-statistical. Moderated nuclear recoil experiments yield mechanisms and rates for the reactions of thermal 18 F atoms. Under our standard experimental conditions from 3.4 x 10 4 to 3.4 x 10 8 labeled product molecules are available for radioassay. This procedure is free from systematic error and the measurements yield exceptional precision and sensitivity because (1) high energy reactions with the thermally active reagents are suppressed. (2) the host environment is rigorously controlled, and (3) the molecular products from many single atom reactions are directly counted. The limitations of this technique are described and results are presented for the reactions of thermal 18 F atoms with CH 4 and C 2 H 4 . (J.P.N.)

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sup 18/F)haloperidol

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

1984-07-01

Syntheses of (/sup 18/F)haloperidol and (/sup 18/F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (/sup 18/F)butyrophenone neuroleptics were prepared in low (<2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added /sup 18/F-neuroleptics were prepared in better (5-17%) yields by /sup 18/F-for-/sup 19/F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

Sources of carrier F-19 in F-18 fluoride

Energy Technology Data Exchange (ETDEWEB)

Link, J. M.; Shoner, S. C.; Krohn, K. A. [University of Washington, Department of Radiology, Molecular Imaging Center, 1959 NE Pacific St., Box 356004, Seattle, WA 98195-6004 (United States)

2012-12-19

Fluorine-18 is used for many PET radiopharmaceuticals. Theoretically {sup 18}F should be carrier free and a good candidate for nanochemistry. However, {sup 18}F has 10 to 1000 times more stable fluorine atoms than radioactive atoms. In order to understand the source of carrier fluoride and other ions associated with {sup 18}F radiosynthesis, anion concentrations of different components of {sup 18}F target systems as well as solvents and chemicals used in radiosynthesis were measured. Results: The enriched water used for production of {sup 18}F had low levels of anions. In general, the sources of anions, particularly of fluoride, were the chemical reagents used for synthesis and trace contaminants in tubing, valves and fittings. A major component of contamination was nitrate from irradiation of dissolved nitrogen gas in the target water.

High specific radioactivity (1R,2S)-4-[{sup 18}F]fluorometaraminol: a PET radiotracer for mapping sympathetic nerves of the heart

Energy Technology Data Exchange (ETDEWEB)

Langer, Oliver; Valette, Heric; Dolle, Frederic E-mail: dolle@dsvidf.cea.fr; Halldin, Christer; Loc' h, Christian; Fuseau, Chantal; Coulon, Christine; Ottaviani, Michele; Bottlaender, Michel; Maziere, Bernard; Crouzel, Christian

2000-04-01

The radiolabeled catecholamine analogue (1R,2S)-6-[{sup 18}F]fluorometaraminol (6-[{sup 18}F]FMR) is a substrate for the neuronal norepinephrine transporter. It has been used as a positron emission tomography (PET) ligand to map sympathetic nerves in dog heart. 6-[{sup 18}F]FMR could be only synthesized with low specific radioactivity, which precluded its use in human subjects. We have recently prepared (1R,2S)-4-[{sup 18}F]fluorometaraminol (4-[{sup 18}F]FMR), a new fluoro-analogue of metaraminol, with high specific radioactivity (56-106 GBq/{mu}mol). In the present study, we demonstrate in rats that 4-[{sup 18}F]FMR possesses similar affinity toward myocardial norepinephrine transport mechanisms as 6-[{sup 18}F]FMR. When compared with control animals, an 80% and 76% reduction in myocardial uptake was observed in animals pretreated with desipramine (an inhibitor of the neuronal norepinephrine transporter) and with reserpine (a blocker of the vesicular storage of monoamines), respectively. The entire radioactivity in rat myocardium represented unmetabolized parent tracer as determined by high performance liquid chromatography analysis of tissue extracts. In dogs, myocardial kinetics of 4-[{sup 18}F]FMR were assessed using PET. A rapid and high uptake was observed, followed by prolonged cardiac retention. A heart-to-lung ratio of 15 was reached 10 min after injection of the radiotracer. Pretreatment with desipramine reduced the heart half-life of 4-[{sup 18}F]FMR by 90% compared with control. Moreover, an infusion of tyramine caused a rapid decline of radioactivity in the heart. This demonstrates that 4-[{sup 18}F]FMR specifically visualizes sympathetic neurons in dog heart. High specific radioactivity 4-[{sup 18}F]FMR is a promising alternative to 6-[{sup 18}F]FMR for myocardial neuronal mapping with PET in humans.

Automated production of [18F]FDDNP using a TRACERlab MXFDG

International Nuclear Information System (INIS)

Vercouillie, J.; Maia, S.; Edmond, P.; Guilloteau, D.; Prenant, Ch.; Deloye, J.B.; Maia, S.; Guilloteau, D.; Guillouet, St.; Barre, L.

2010-01-01

[ 18 F]FDDNP has been recently described as a potent tracer to image amyloid plaques in vivo by positron emission tomography. Such a tool will be advisable to diagnose patient with mild cognitive impairment, to follow the disease progression and to evaluate new therapies. To make this radiopharmaceutical affordable for the clinicians, we developed an automated method for [ 18 F]FDDNP radiosynthesis using a commercial [ 18 F]FDG unit. Radiolabeling with fluorine-18 was carried out by a [ 18 F]fluoro-detosylation reaction on the precursor 2-(1-{6-[(2-tosyloxyoethyl)(methyl)amino]-2- naphthyl}ethylidene)malononitrile. The reaction was performed in acetonitrile for 15 min at 90 C, and then the reaction mixture was injected into a semi-preparative high-pressure liquid chromatography. The desire [ 18 F]FDDNP fraction was collected, and an SPE was performed. The [ 18 F]FDDNP was formulated in a sodium chloride/ethanol solution followed by a sterile filtration. Stability of [ 18 F]FDDNP was studied after 4 h and radiochemical purity of [ 18 F]FDDNP remained ≥98%. The overall decay-corrected radiochemical yield was 15±3% (n = 8). Radiochemical purity was ≥98% and the specific activity was 164±25 GBq/μmol at EOS. Pharmaceutical controls, bio-burden, sterility, bacterial endotoxin and residual solvent tests were performed. The results were in accordance with the European Pharmacopoeia and demonstrated our ability to produce [ 18 F]FDDNP with a pharmaceutical grade and a high reproducibility. (authors)

High and typical 18F-FDG bowel uptake in patients treated with metformin

International Nuclear Information System (INIS)

Gontier, Eric; Bonardel, Gerald; Mantzarides, Marina; Foehrenbach, Herve; Fourme, Emmanuelle; Wartski, Myriam; Pecking, Alain-Paul; Alberini, Jean-Louis; Blondet, Cyrille; Le Stanc, Elise

2008-01-01

This prospective and bi-centric study was conducted in order to determine the impact of antidiabetic treatments (AD) on 18 F-FDG bowel uptake in type 2 diabetic patients. Fifty-five patients with previously diagnosed and treated type 2 diabetes mellitus (group 1) were divided in two subgroups: AD treatment including metformin (n=32; group 1a) and AD treatment excluding metformin (n=23; group 1b). The 95 patients without diabetes mellitus made up controls (group 2). 18 F-FDG uptake in small intestine and colon was visually graded and semi-quantitatively measured using the maximum standardized uptake value. 18 F-FDG bowel uptake was significantly increased in AD patients (group 1) as compared to controls (group 2) (p 18 F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an 18 F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment. (orig.)

PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer {sup 18}F-AlF-NOTA-PRGD2

Energy Technology Data Exchange (ETDEWEB)

Gao, Haokao [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China); National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Lang, Lixin; Guo, Ning; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Cao, Feng [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)

2012-04-15

The {alpha}{sub v}{beta}{sub 3} integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin {alpha}{sub v}{beta}{sub 3}-targeting positron emission tomography (PET) probe, {sup 18}F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model. Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, {sup 18}F-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of {sup 18}F-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results. Myocardial origin of the {sup 18}F-AlF-NOTA-PRGD2 accumulation was confirmed by {sup 18}F-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of {sup 18}F-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 {+-} 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 {+-} 0.16 and 0.55 {+-} 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 {+-} 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer {sup 18}F-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 {+-} 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin {beta

A pilot study for texture analysis of {sup 18}F-FDG and {sup 18}F-FLT-PET/CT to predict tumor recurrence of patients with colorectal cancer who received surgery

Energy Technology Data Exchange (ETDEWEB)

Nakajo, Masatoyo; Tani, Atsushi; Jinguji, Megumi; Yoshiura, Takashi [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kajiya, Yoriko; Nakajo, Masayuki [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Kitazono, Masaki [Nanpuh Hospital, Department of Surgery, Kagoshima (Japan)

2017-12-15

This retrospective study was done to examine whether the heterogeneity in primary tumor F-18-fluorodeoxyglucose ({sup 18}F-FDG) and {sup 18}F-3'-fluoro-3'-deoxythymidine ({sup 18}F-FLT) distribution can predict prognosis of patients with colorectal cancer who received surgery. The enrolled 32 patients with colorectal cancer underwent both {sup 18}F-FDG- and {sup 18}F-FLT-PET/CT studies before surgery. Clinicopathological factors, stage, SUVmax, SUVmean, metabolic tumor volume (SUV ≥ 2.5), total lesion glycolysis, total lesion proliferation and seven texture heterogeneity parameters (coefficient of variation, local parameters: entropy, homogeneity, and dissimilarity; and regional parameters: intensity variability [IV], size-zone variability [SZV], and zone percentage [ZP]) were obtained. Progression free survival (PFS) was calculated by the Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. Eight patients had eventually come to progression, and 24 patients were alive without progression during clinical follow-up [mean follow-up PFS; 55.9 months (range, 1-72)]. High stage (p = 0.004), high {sup 18}F-FDG-IV (p = 0.015), high {sup 18}F-FDG-SZV (p = 0.013) and high {sup 18}F-FLT-entropy (p = 0.015) were significant in predicting poor 5-year PFS. Other parameters did not predict the disease outcome. At bivariate analysis, disease event hazards ratios for {sup 18}F-FDG-IV and {sup 18}F-FDG-SZV remained significant when adjusted for stage and {sup 18}F-FLT-entropy ({sup 18}F-FDG-IV; p = 0.004 [adjusted for stage], 0.007 [adjusted for {sup 18}F-FLT-entropy]; {sup 18}F-FDG-SZV; p = 0.028 [adjusted for stage], 0.040 [adjusted for {sup 18}F-FLT-entropy]). {sup 18}F-FDG PET heterogeneity parameters, IV and SZV, have a potential to be strong prognostic factors to predict PFS of patients with surgically resected colorectal cancer and are more useful than {sup 18}F-FLT-PET/CT heterogeneity parameters. (orig.)

Additional value of 16{alpha}-[{sup 18}F]fluoro-17{beta}-oestradiol PET for differential diagnosis between uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [{sup 18}F]fluorodeoxyglucose PET

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Yoshio; Kurokawa, Tetsuji; Kotsuji, Fumikazu [University of Fukui, Department of Gynecology, Faculty of Medical Sciences, Fukui (Japan); Kiyono, Yasushi; Tsujikawa, Tetsuya; Okazawa, Hidehiko [University of Fukui, Biomedical Imaging Research Center, Fukui (Japan)

2011-10-15

Pathological data suggest that the rate of oestrogen receptor (ER) expression in uterine sarcoma is significantly lower than in leiomyoma. The present study aimed to investigate whether ER expression using ER imaging agents for positron emission tomography (PET), of which the most successful has been 16{alpha}-[{sup 18}F]-fluoro-17{beta}-oestradiol (FES), is able to add useful information to the differential diagnosis of uterine sarcoma and leiomyoma in patients with positive or equivocal findings on [{sup 18}F]fluorodeoxyglucose (FDG) PET. A total of 76 patients with suspected uterine sarcoma based on ultrasound and magnetic resonance imaging findings from 2007 to 2010 were enrolled. Twenty-four of the present patients were referred for FES PET because of FDG PET findings that showed equivocal or positive FDG uptake. PET images were quantitatively evaluated with reference to histopathological findings. Receiver-operating characteristic analysis was performed to determine the optimal cutoff value to differentiate uterine sarcoma and leiomyoma. Of the 24 patients, 11 had a final diagnosis of uterine sarcoma, while 13 had leiomyoma. The sensitivity, specificity and accuracy of an FDG to FES standardized uptake value (SUV) ratio greater than 2.0 were significantly higher using Cochran's Q test (p = 0.024) when compared with FDG PET greater than 3.0 alone (90.9 vs 81.8%, 92.3 vs 84.6% and 91.3 vs 83.3%, respectively). Additional FES PET findings confirmed uterine sarcoma in 91.3% of a selected group of patients with equivocal or positive FDG uptake. (orig.)

Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET

International Nuclear Information System (INIS)

Ossenkoppele, Rik; Tolboom, Nelleke; Adriaanse, Sofie F.; Foster-Dingley, Jessica C.; Boellaard, Ronald; Yaqub, Maqsood; Windhorst, Albert D.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van; Barkhof, Frederik; Scheltens, Philip; Flier, Wiesje M. van der

2012-01-01

[ 11 C]PIB and [ 18 F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [ 18 F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls. Longitudinal, paired, dynamic [ 11 C]PIB and [ 18 F]FDDNP (90 min each) and static [ 18 F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [ 11 C]PIB and [ 18 F]FDDNP images of binding potential (BP ND ) and [ 18 F]FDG standardized uptake value ratio (SUVr) images were generated. A significant increase in global cortical [ 11 C]PIB BP ND was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [ 11 C]PIB BP ND in MCI patients was most prominent in the lateral temporal lobe (p 18 F]FDDNP, no changes in global BP ND were found. [ 18 F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p 11 C]PIB binding (ρ = -0.42, p 18 F]FDG uptake (ρ = 0.54, p 18 F]FDDNP binding (ρ = -0.18, p = 0.35) were not. [ 11 C]PIB and [ 18 F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [ 18 F]FDDNP seems to be less useful for examining disease progression. (orig.)

Clinical Relevance of 18F-Sodium Fluoride Positron-Emission Tomography in Noninvasive Identification of High-Risk Plaque in Patients With Coronary Artery Disease.

Science.gov (United States)

Lee, Joo Myung; Bang, Ji-In; Koo, Bon-Kwon; Hwang, Doyeon; Park, Jonghanne; Zhang, Jinlong; Yaliang, Tong; Suh, Minseok; Paeng, Jin Chul; Shiono, Yasutsugu; Kubo, Takashi; Akasaka, Takashi

2017-11-01

18 F-sodium fluoride ( 18 F-NaF) positron-emission tomography has been introduced as a potential noninvasive imaging tool to identify plaques with high-risk characteristics in patients with coronary artery disease. We sought to evaluate the clinical relevance of 18 F-NaF uptake using optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography in patients with coronary artery disease. The target population consisted of 51 prospectively enrolled patients (93 stenoses) who underwent 18 F-NaF positron-emission tomography before invasive coronary angiography. 18 F-NaF uptake was compared with IVUS- and OCT-derived plaque characteristics. In the coronary computed tomography angiography subgroup (46 lesions), qualitative lesion characteristics were compared between 18 F-NaF-positive and 18 F-NaF-negative plaques using adverse plaque characteristics. The plaques with 18 F-NaF uptake showed significantly higher plaque burden, more frequent posterior attenuation and positive remodeling in IVUS, and significantly higher maximum lipid arc and more frequent microvessels in OCT (all P characteristics. The 18 F-NaF tissue-to-background ratio in plaques with high-risk characteristics was significantly higher than in those without (1.09 [95% confidence interval, 0.85-1.34] versus 0.62 [95% confidence interval, 0.42-0.82], P characteristics between 18 F-NaF-positive and 18 F-NaF-negative plaques in the coronary computed tomography angiography subgroup (85.2% versus 78.9%; P =0.583). This study's results suggest that 18 F-NaF positron-emission tomography can be a useful noninvasive diagnostic tool to identify and localize plaque with high-risk characteristics. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02388412. © 2017 American Heart Association, Inc.

Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine.

Science.gov (United States)

Chin, Bennett B; McDougald, Darryl; Weitzel, Douglas H; Hawk, Thomas; Reiman, Robert E; Zalutsky, Michael R; Vaidyanathan, Ganesan

2017-01-01

Amino acid transporters, such as LAT1, are overexpressed in aggressive prostate and breast carcinomas, directly influencing pathways of growth and proliferation. The purpose of this study was to synthesize and characterize a novel 18F labeled leucine analog, 5-[18F]fluoroleucine, as a potential imaging agent for aggressive tumors which may not be amenable to imaging by FDG PET. 5-fluoroleucine was synthesized and characterized, and its 18F-labeled analog was synthesized from a mesylate precursor. First, breast cancer cell line assays were performed to evaluate uptake of 3H- or 14C-labeled L-leucine and other essential amino acids. Both L-leucine and 5- [18F]fluoroleucine were tested for uptake and accumulation over time, and for uptake via LAT1. Biodistribution studies were performed to estimate radiation dosimetry for human studies. Small animal PET / CT studies of a breast cancer were performed to evaluate in vivo 5-[18F]fluoroleucine tumor uptake. Breast cancer cell lines showed increasing high net accumulation of L-[14C]leucine. Both L-leucine and 5-[18F]fluoroleucine showed increasing uptake over time in in vitro tumor cell assays, and uptake was also shown to occur via LAT1. The biodistribution study of 5-[18F]fluoroleucine showed rapid renal excretion, no significant in vivo metabolism, and acceptable dosimetry for use in humans. In vivo small animal PET / CT imaging of a breast cancer xenograft showed uptake of 5- [18F]fluoroleucine in the tumor, which progressively increased over time. 5-[18F]fluoroleucine is a leucine analog which may be useful in identifying tumors with high or upregulated expression of amino acid transporters, providing additional information that may not be provided by FDG PET. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

4- 18F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4- 18F]fluorophenol

International Nuclear Information System (INIS)

Ludwig, Thomas; Ermert, Johannes; Coenen, Heinz H.

2002-01-01

This paper describes the improved synthesis of n.c.a. 4- 18 F]fluorophenol for the preparation of 18 F-labeled alkylarylethers. Nucleophilic fluorination of substituted benzophenone derivatives yielded n.c.a. 4- 18 F]fluoro-4'-substituted benzophenones with 80- 90 % RCY, which were converted to benzoic acid phenylesters by treatment with peracetic acid. Strong electron-withdrawing substituents like nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration resulting in the formation of corresponding benzoic acid fluorophenylesters. N.c.a. 18 F]fluorophenol is almost quantitatively formed after hydrolysis and can easily be converted with alkylhalides into n.c.a. 18 F]fluoroarylalkylethers

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

International Nuclear Information System (INIS)

Hultsch, Christina; Schottelius, Margret; Auernheimer, Joerg; Alke, Andrea; Wester, Hans-Juergen

2009-01-01

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 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 currently

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

Science.gov (United States)

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

A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

Science.gov (United States)

Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

2018-04-01

In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

International Nuclear Information System (INIS)

Ryzhikov, Nikolaj N.; Seneca, Nicholas; Krasikova, Raisa N.; Gomzina, Natalia A.; Shchukin, Evgeny; Fedorova, Olga S.; Vassiliev, Dmitrij A.; Gulyas, Balazs; Hall, Hakan; Savic, Ivanka; Halldin, Christer

2005-01-01

A straightforward method for the preparation of no-carrier-added (n.c.a.) [ 18 F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K 18 F/kryptofix complex in DMF at 160 deg. C for 30 min and equimolar ratio [K/K2.2.2] +18 F - /precursor. Under these conditions, an 18 F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [ 18 F]flumazenil as for [ 11 C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [ 18 F]Flumazenil is a suitable radioligand for PET assessment of the BZR

The optimization of 18F-nucleophilic fluorination reaction and its application in synthesis of VMAT2 imaging tracer: [18F]AV-133

International Nuclear Information System (INIS)

Liu Yajing; Zhu Lin; Karl, P.; Qu Wenchao

2010-01-01

Objective: The nucleophilic introduction of n.c.a. [ 18 F]F- into alkanes by nucleophilic reaction is the main method of preparing 18 F-labelled radiopharmaceuticals, and the efficient and rapid reaction is important in 18 F-labelled radiopharmaceuticals. Method: Using 2-(3-substitute propoxy)naphthalene as model compound, the optimal reaction condition was achieved by comparing the different [ 18 F]fluorination condition: 1)different leaving groups (-OTs, -I, -Br and -Cl), 2) different [ 18 F]fluorination catalysts (Kryptofix222/K 2 CO 3 and TBAHCO 3 ), 3) different reaction solvent (ACN, DMSO and DMF), 4) [ 18 F]fluorination temperature (40, 50 and 60 degree C) and 5) reaction time. The radiochemical yields were analyzed by TLC and HPLC. VMAT2 imaging tracer [ 18 F]AV-133 was synthesized under the optimal conditions. Results: From the experiment results, the reation activity was the highest when using -OTs as the leaving group, followed by -I and -Br, -Clunder the [ 18 F]fluorination condition of using K222/K 2 CO 3 as catalyst and ACN as solvent. And also, the radiochemical yield raised as the reaction time and temperature increased. The higher temperature, the shorter time to reach the equilibrium. When changing the solvent from ACN to DMSO, the radiochemical yields were increased. On the contrary, the radiochemical yields were decreasing by using DMF. Comparing the catalyst K222/K 2 CO 3 with TBAHCO 3 , the [ 18 F] fluorination of -OTs gave a higher radiochemical yield in the presence of K222/K 2 CO 3 . So the optimized [ 18 F]fluorination reaction condition was that choosing -OTs as the leaving group, the [ 18 F]fluorination reaction was efficient and gave higher radiochemical yield catalyzed by K222/K 2 CO 3 in DMSO at high temperature. [ 18 F]fluorination of AV-244 was found to provide the VMAT2 imaging tracer [ 18 F]AV-133 in 80 ± 2% radiochemical yield after reaction at 120 degree C for 3 min under optimized conditions. Conclusion: We have described an

Radiolysis of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) and the role of ethanol and radioactive concentration

Energy Technology Data Exchange (ETDEWEB)

Jacobson, Mark S. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States)], E-mail: jacobson.mark17@mayo.edu; Dankwart, Heather R. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States); Mahoney, Douglas W. [Division of Biostatistics, Mayo Clinic, Rochester, MN (United States)

2009-06-15

Radiolysis is the process by which radioactively labeled compounds degrade. Many positron emission tomography (PET) radiopharmaceuticals produced with high radioactive concentrations and specific activities exhibit low radiochemical purity because of radiolysis. Little data exist that describe the radiolytic decomposition of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG). The objective of our study was to profile the degradation of [{sup 18}F]FDG at various radioactive concentrations by measuring radiochemical purity at different time intervals and to study the effects of ethanol, a well-known reductant stabilizer of [{sup 18}F]FDG preparations.

Unusual soft tissue uptake of F-18 sodium fluoride in three patients undergoing F-18 NaF PET/CT bone scans for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Hawkins, Andrew S.; Howard, Brandon A. [Div. of Nuclear Medicine, Dept. of Radiology, Duke University Medical Center, Durham (United States)

2017-09-15

Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.

Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis.

Science.gov (United States)

Matsui, Tamiko; Nakata, Norihito; Nagai, Shigenori; Nakatani, Akira; Takahashi, Miwako; Momose, Toshimitsu; Ohtomo, Kuni; Koyasu, Shigeo

2009-06-01

Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. (18)F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between (18)F-FDG accumulation and RA pathology, we assessed (18)F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and (3)H-FDG uptake in vitro using various cells involved in arthritis. (18)F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the (18)F-FDG accumulation was compared with the histologic findings. (3)H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to (18)F-FDG accumulation. In addition, the influence on (3)H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. (18)F-FDG PET depicted swollen joints, and (18)F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of (18)F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro (3)H-FDG uptake assay, fibroblasts showed the highest (3)H-FDG uptake, followed by neutrophils. Although only a small amount of (3)H-FDG was incorporated by resting macrophages, a dramatic increase in (3)H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFalpha and IL-1, and hypoxia. Although neutrophils showed relatively high (3)H-FDG uptake without activation, no increase in (3)H-FDG uptake was observed in response to inflammatory cytokines. (3)H-FDG uptake by T cells was much lower than

Comparison of [18F]FLT and [18F]FDG in in vitro cancer cell uptake and glucose effect

International Nuclear Information System (INIS)

Soo Jung Lim; Jin-Sook Ryu; Heuiran Lee; Seok Young Kim; Seung Jun Oh; Dae Hyuk Moon

2004-01-01

[18F]FLT is a new radiopharmaceutical for cell proliferation. We compared [18F]FLT and [18F]FDG in in vitro cancer cell uptake and glucose effect. Method: In vitro cancer cell uptake of [18F]FLT was evaluated using SCC7(mouse squamous cell carcinoma). At 24 hours after seeding 1 x 106 cells/well in 6 well plates with RPMI 1640 medium, culture media were changed to medium with glucose free or glucose concentration of 100 mg/dl. Then, [18F]FLT 5 μCi/50 ml was added to each well. After incubation for 30, 60, 90, 120 minutes, cells were washed twice by PBS, and harvested using 0.25% trypsin-EDTA. After centrifugation and counting at gamma counter, cell uptake was calculated by % activity of cellular uptake to total activity of cell and supernatant. For comparison, same tumor cell uptake experiment was performed with [18F]FDG. Results: After incubation with SCC7 cell line for 30, 60, 90, 120 minutes, [18F]FLT showed 1.95%, 2.17%, 2.10% and 2.80% of cell uptake in glucose free media, respectively. The results [18F]FLT uptake in glucose 100 mg/dl media were 1.82%, 1.87%, 1.97%, and 2.94%, respectively. The results of [18F]FDG in glucose free media were 2.50%, 3.47%, 5.04%, and 10.4%, whereas those in glucose 100 mg/dl media were 1.60%, 1.79%, 1.53%, and 1.82%, respectively. Conclusion: In contrast to [18F]FDG, [18F]FLT uptake in cancer cell was not affected by glucose concentration. In physiologic glucose concentration, [18F]FLT uptake in SCC7 cell line was significantly higher than [18F]FDG uptake after 120 minutes incubation. In [18F]FLT PET imaging may not need fasting for preparation before imaging study. (authors)

Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

Science.gov (United States)

Vercellino, Laetitia; Groheux, David; Thoury, Anne; Delord, Marc; Schlageter, Marie-Hélène; Delpech, Yann; Barré, Emmanuelle; Baruch-Hennequin, Valérie; Tylski, Perrine; Homyrda, Laurence; Walker, Francine; Barranger, Emmanuel; Hindié, Elif

2012-11-01

Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Comparison in animal models of 18F-spiroperidol and 18F-haloperidol: potential agents for imaging the dopamine receptor

International Nuclear Information System (INIS)

Welch, M.J.; Kilbourn, M.R.; Mathias, C.J.; Mintun, M.A.; Raichle, M.E.

1983-01-01

Fluorine-18-labeled haloperidol and spiroperidol have been prepared by an exchange reaction using the corresponding non-labeled compound or the nitro analog. Studies in rats have shown that the distribution of labeled spiroperidol has a high striatum to cerebellum ratio which is not observed with haloperidol. A ratio of 10.66 +/- 1.6 is obtained two hours after administration of the 18 F-spiroperidol. When 18 F-spiroperidol was administered to a baboon and tomographic images obtained, the dopamine receptor rich areas were clearly visualized two hours after administration

Lithium abundances in high- and low-alpha halo stars

DEFF Research Database (Denmark)

Nissen, P. E.; Schuster, W. J.

2012-01-01

A previous study of F and G main-sequence stars in the solar neighborhood has revealed the existence of two distinct halo populations with a clear separation in [alpha /Fe] for the metallicity range -1.4 < [Fe/H] < -0.7. The kinematics of the stars and models of galaxy formation suggest that the ......A previous study of F and G main-sequence stars in the solar neighborhood has revealed the existence of two distinct halo populations with a clear separation in [alpha /Fe] for the metallicity range -1.4 ... that the ``high-alpha '' stars were formed in situ in the inner parts of the Galaxy, whereas the ``low-alpha '' ones have been accreted from satellite galaxies. In order to see if there is any systematic difference in the lithium abundances of high- and low-alpha stars, equivalent widths of the iLi 6707.8 Å line...... have been measured from VLT/UVES and NOT/FIES spectra and used to derive Li abundances. Furthermore, stellar masses are determined from evolutionary tracks in the log T_eff - log g diagram. For stars with masses 0.7 lithium abundance...

Comparative studies of epibatidine derivatives [{sup 18}F]NFEP and [{sup 18}F]N-Methyl-NFEP: kinetics, nicotine effect, and toxicity

Energy Technology Data Exchange (ETDEWEB)

Ding Yushin E-mail: ding@bnl.gov; Molina, Patricia E.; Fowler, Joanna S.; Logan, Jean; Volkow, Nora D.; Kuhar, Michael J.; Carroll, F. Ivy

1999-01-01

We have previously shown that [{sup 18}F]norchlorofluoroepibatidine ([{sup 18}F]NFEP) would be an ideal radiotracer for positron emission tomography (PET) imaging of nicotinic acetylcholine receptors (nAChR); however, its high toxicity is a limiting factor for human studies. We, therefore, synthesized its N-methyl derivative ([{sup 18}F]N-Me-NFEP) and carried out comparative studies. The distribution volumes for different brain regions were higher for [{sup 18}F]N-Me-NFEP than those for [{sup 18}F]NFEP (average: 52.5 {+-} 0.9 vs. 36.4 {+-} 0.7 for thalamus), though the distribution volume (DV) ratios were similar (3.93 {+-} 0.27 vs. 3.65 {+-} 0.19 for thalamus to cerebellum). Treatment with nicotine reduced the binding of both radiotracers. Toxicology studies in awake rats showed that N-methyl-NFEP has a lower mortality (0 vs. 30%) and smaller effect on plasma catecholamines than NFEP at a dose of 1.5 {mu}g/kg. However, marked alterations in cardiorespiratory parameters were observed after injection of N-methyl-NFEP (0.5 {mu}g/kg, IV) to an awake dog. methresults suggest that although the binding characteristics of [{sup 18}F]NFEP and [{sup 18}F]N-Me-NFEP appear to be ideally suited for PET imaging studies of the human brain, their relatively small safety margin will limit their use in humans.

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

Energy Technology Data Exchange (ETDEWEB)

Yao, C.-H. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Lin, K.-J. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Weng, C.-C. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Hsiao, I.-T. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Ting, Y.-S. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Yen, T.-C. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China); Jan, T.-R. [Department and Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104 (United States); Kung, M.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Wey, S.-P., E-mail: spwey@mail.cgu.edu.t [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, 259 Wen-Hua 1st Road, Kweishan, Taoyuan 333, Taiwan (China)

2010-12-15

We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of {sup 18}F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of {beta}-amyloid (A{beta}) plaques in the brain of Alzheimer's disease patients. [{sup 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 [{sup 18}F]AV-45 reached as high as 470{+-}135 TBq/mmol (n=19). The present studies show that [{sup 18}F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use.

Clinical studies of 18F-FDG and 18F-FP-β-CIT PET imaging in hemi-Parkinson's disease

International Nuclear Information System (INIS)

Zhao Jun; Lin Xiangtong; Guan Yihui; Zuo Chuantao; Zhang Zhengwei; Wang Jian; Sun Bomin; Chen Zhengping

2003-01-01

Objective: To study the characteristics of 18 F-fluorodeoxyglucose (FDG) and 18 F-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) PET imaging in patients with hemi-Parkinson's disease (hemi-PD) and to assess their value in early diagnosis. Methods: 34 cases of hemi-PD (Hoehn and Yahr stage I-II) and 16 normal control subjects were selected for this study. 16 patients were performed with 18 F-FDG PET imaging, 18 patients with 18 F-FP-β-CIF, while 6 patients of them both 18 F-FDG and 18 F-FP-β-CIT. 30 min after injection of 185-259 MBq 18 F-FDG, 3D brain scans were acquired. Region of interest (ROI) analysis and statistical parametric mapping (SPM) were applied. 18 F-FP-β-CIT PET imaging was carried out 2-3 h post injection, and (ROI-cerebellum)/cerebellum ratio was calculated. Results: In right hemi-PD, reductions in 18 F-FDG metabolism were observed in the left basal ganglia compared with control group, but with no significant difference (P>0.05). The results of SPM analysis showed that a significant reduction in FDG uptake in the left superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and left middle temporal gyrus, whereas a significant increase in the bilateral precentral gyrus , superior parietal lobule, left middle occipital gyrus and left thalamus as compared with the control group. There was a significant reduction in 18 F-FP-β-CIT uptake in putamen, its reduction was found not only in the contralateral putamen, but also in the ipsilateral ones, and more pronounced in the contralateral posterior putamen. Conclusions: 18 F-FDG PET imaging is non-specific for the early diagnosis of PD. 18 F-FP-β-CIT PET imaging could find the changes of striatum dopamine transporter at early stage, therefore it was helpful for early diagnosis and differential diagnosis of PD. Combined with 18 F-FDG PET imaging, the changes of local cerebral glucose metabolism in PD could also be evaluated

18F-Labelling of electron rich iodonium ylides

DEFF Research Database (Denmark)

Petersen, I N; Villadsen, J; Hansen, H D

2017-01-01

in the pursuit of (18)F-labelled 5-HT2A receptor agonist PET-ligands. Subsequent evaluation in pigs showed high brain uptake of the PET ligands but a blocking dose of ketanserin did not significantly reduce the signal in relevant brain regions - indicating that the ligands do not interact specifically with the 5......(18)F-Labelling of aromatic moieties was limited to electron deficient aromatic systems for many years but recent developments have provided access to the direct labelling of electron rich aromatic systems. Herein we report the synthesis and (18)F-labelling of iodonium ylide precursors...

(18)F-Labelling of electron rich iodonium ylides

DEFF Research Database (Denmark)

Petersen, I N; Villadsen, J; Hansen, H D

2017-01-01

in the pursuit of (18)F-labelled 5-HT2A receptor agonist PET-ligands. Subsequent evaluation in pigs showed high brain uptake of the PET ligands but a blocking dose of ketanserin did not significantly reduce the signal in relevant brain regions - indicating that the ligands do not interact specifically with the 5......(18)F-Labelling of aromatic moieties was limited to electron deficient aromatic systems for many years but recent developments have provided access to the direct labelling of electron rich aromatic systems. Herein we report the synthesis and (18)F-labelling of iodonium ylide precursors...

Evaluation of F-18-labeled 5-iodocytidine ({sup 18}F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

Energy Technology Data Exchange (ETDEWEB)

Chan, Pei-Chia; Wu, Chun-Yi; Chang, Wen-Yi; Chang, Wei-Ting [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Alauddin, Mian [Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, TX, 77054 (United States); Liu, Ren-Shan [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Lin, Wuu-Jyh [Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 32546, Taiwan (China); Chen, Fu-Du [College of Health and Leisure Science, TransWorld University, Yunlin, 64063, Taiwan (China); Chen, Chuan-Lin, E-mail: clchen2@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Wang, Hsin-Ell, E-mail: hewang@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China)

2011-10-15

Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[{sup 18}F]fluoro-{beta}-D-arabinofuranosyl)-5-iodocytosine ({sup 18}F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ({sup 18}F-FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil({sup 18}F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6{+-}25.1, 76.3{+-}18.2 and 247.2{+-}37.2, respectively. In biodistribution studies, {sup 18}F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with {sup 18}F-FIAU (15.8) but lower than {sup 18}F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue {sup 18}F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. {sup 18}F-FIAC may be regarded as the prodrug of {sup 18}F-FIAU in vivo.

Aspects of the production of 18F-2-deoxy-2-fluoro-D-glucose via 18F2 with a tandem Van de Graaf accelerator

International Nuclear Information System (INIS)

Shaughnessy, W.J.; Gatley, S.J.; Hichwa, R.D.; Lieberman, L.M.; Nickles, R.J.

1981-01-01

During deuteron irradiation of 100 psig neon containing 1-2% of elemental fluorine, the induced 18 F partitions into three main fractions. About 50% remains in the passivated nickel target after elution of the gas mixture. Some of the gaseous 18 F is capable of performing fluorination reactions and is presumed to be 18 F 2 : the rest is a mixture of at least two unreactive gases, one of which behaves on gas chromatography like CF 4 . The ratio of reactive to unreactive gaseous 18 F decreases with longer irradiation times but increases when the target gas is cooled to -30C during bombardment. Reaction of the presumed 18 F 2 with 4.5,6-triacetyl-D-glucal, essentially by the published method, yielded 18 F-2-deoxy-2-fluoro-4,5,6-triacetyl-x-D-glucosyl fluoride and the corresponding β-D-mannosyl fluoride. These were separated either by column chromatography or preparative TLC, using plates with a pre-absorbent layer. Hydrolysis of the glucoyl fluoride gave 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-2FDG) with a decay-corrected yield of about 10% based on 18 F trapped by the triacetylglucal. The 60 min organ distribution of 18 F from 18 F-2-FDG in tumor bearing rats was compared with the corresponding distribution after administration of 18 F-3-deoxy-3-fluoro-D-glucose ( 18 F-3FDG). Organ/blood ratios were uniformly higher for 18 F-2FDG than for no carrier added 18 F-3FDG; only heart, brain and thyroid had ratios greater than unity. Added carrier 3-FDG further lowered organ/blood ratios. The main conclusion drawn from this animal work is that 18 F-3FDG is unlikely to rival 18 F-2FDG for nuclear medicine studies, where high target /blood ratios (obtained by metabolic trapping as the sugar-6-phosphate) are necessary. However 18 F-3FDG may be useful for estimating the concentration of free glucose in organs if further work confirms that it is an essentially non-metabolized analog of glucose. (author)

Combination of nitric oxide stimulation with high-dose 18F-FDG promotes apoptosis and enhances radiation therapy of endothelial cells

International Nuclear Information System (INIS)

Paik, Jin-Young; Park, Jin-Won; Jung, Kyung-Ho; Lee, Eun Jeong; Lee, Kyung-Han

2012-01-01

Introduction: High-dose 18 F-FDG can provide targeted nuclear therapy of cancer. Endothelial cell injury is a key determinant of tumor response to radiotherapy. Here, we tested the hypothesis that activation of endothelial cell glycolytic metabolism with nitric oxide can enhance the therapeutic effect of high-dose 18 F-FDG. Methods: Calf pulmonary artery endothelial (CPAE) cells were treated with graded doses of 18 F-FDG. Glycolysis was stimulated by 24 h of exposure to the nitric oxide donor, sodium nitroprusside (SNP). Cell viability was assessed by MTT and clonogenic assays. Apoptosis was evaluated by ELISA of cytosolic DNA fragments and Western blots of cleaved caspase-3. Results: SNP stimulation (0.1 and 1 mM) augmented CPAE cell 18 F-FDG uptake to 2.6- and 4.6-fold of controls without adverse effects. Treatment with 333 μCi/ml 18 F-FDG alone reduced viable cell number to 35.4% of controls by Day 3. Combining 0.1 mM SNP stimulation significantly enhanced the killing effect, reducing cell numbers to 19.2% and 39.2% of controls by 333 and 167 μCi/ml of 18 F-FDG, respectively. 18 F-FDG also suppressed clonogenic survival to 80.8% and 43.2% of controls by 83 and 167 μCi/ml, which was again intensified by SNP to 59.7% and 21.1% of controls. The cytotoxic effect of 18 F-FDG was attributed to induction of apoptosis as shown by increased cytosolic fragmented DNA and cleaved caspase-3 levels (26.4% and 30.7% increases by 167 μCi/ml). Combining SNP stimulation significantly increased both of these levels to 1.8-fold of control cells. Conclusion: High-dose 18 F-FDG combined with nitric oxide-stimulated glycolysis is an effective method to inhibit endothelial cell survival and promote apoptosis. These results suggest a potential role of this strategy for targeted radiotherapy of angiogenic vasculature.

Catabolism of 6-ketoprostaglandin F1alpha by the rat kidney cortex.

Science.gov (United States)

Pace-Asciak, C R; Domazet, Z; Carrara, M

1977-05-25

Homogenates of the rat kidney cortex converted 5,8,9,11,12,14,15-hepta-tritiated 6-ketoprostaglandin F 1alpha into one major product identified by gas chromatography-mass spectrometry of the methoxime-methyl ester trimethylsilyl ether derivative as 6,15-diketo-9,11-dihydroxyprost-13-enoic acid. The sequence of derivatisation i.e. methoximation prior to methylation, was crucial as methylation of 15-keto catabolites of the E, F and 6-keto-F series affords degradation products. The corresponding 15-keto-13,14-dihydro catabolite was formed in much smaller quantities. Time course studies indicated that 6-keto-prostaglandin F1alpha was catabolised at a slower rate (about 2-5 fold) than prostaglandin F1alpha. The catabolic activity was blocked by NADH.

Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU)

International Nuclear Information System (INIS)

Chen, Kai; Li Zibo; Conti, Peter S.

2012-01-01

Objectives: [ 18 F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [ 18 F]-FMAU synthesis are time-consuming, resulting in low radiochemical yield and inconvenient applications for the clinic. We have previously reported the use of Friedel-Crafts catalysts for an improved synthesis of [ 18 F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [ 18 F]-FMAU in comparison with conventional thermal conditions. Methods: A simplified one-pot synthesis of [ 18 F]-FMAU was developed under microwave conditions. Various reaction times, temperatures, and microwave powers were systematically explored to optimize the coupling reaction of 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose ([ 18 F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf). Results: Microwave significantly enhanced the coupling efficiency of [ 18 F]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 °C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [ 18 F]-FMAU. The overall radiochemical yield was 20 ± 4% (decay corrected, n = 3). Radiochemical purity was > 99% and specific activity was > 400 mCi/μmol. The α/β anomer ratio was 1:2. The radiosynthesis time was about 90 min from the end of bombardment. Conclusions: A reliable microwave-assisted approach has been developed for routine synthesis of [ 18 F]-FMAU. The new approach affords a simplified process with shorter synthesis time and higher radiochemical yield as compared to conventional heating. A fully automated microwave-assisted synthesis of [ 18 F]-FMAU can be readily achieved under new reaction conditions.

Radiosynthesis and biological evaluation of 18F-labeled 4-anilinoquinazoline derivative (18F-FEA-Erlotinib) as a potential EGFR PET agent.

Science.gov (United States)

Huang, Shun; Han, Yanjiang; Chen, Min; Hu, Kongzhen; Qi, Yongshuai; Sun, Penghui; Wang, Men; Wu, Hubing; Li, Guiping; Wang, Quanshi; Du, Zhiyun; Zhang, Kun; Zhao, Suqing; Zheng, Xi

2018-04-01

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1N-(3-(1-(2- 18 F-fluoroethyl)-1H-1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine ( 18 F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18 F-FEA-Erlotinib was achieved within 50min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18 F-FEA-Erlotinib after incubated in PBS and FBS for 2h. Cellular uptake and efflux experiment results indicated the specific binding of 18 F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18 F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18 F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18 F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

Energy Technology Data Exchange (ETDEWEB)

Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

2010-03-15

In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

18F based radiopharmaceuticals and automation of synthesis. New 18F radiopharmaceuticals

International Nuclear Information System (INIS)

Garg, P.K.; Garg, S.

2007-01-01

Fluorine-18 is one of the most commonly used positron emitting isotopes for clinical and research needs with a physical half-life of 110 min. PET isotopes deposit higher radiation absorbed dose than nuclear medicine isotopes. Because of their relatively short half-life, larger quantities of these isotopes are used at the start of synthesis. Therefore, increased shielding and remote automated synthesis are essential for their safe handling. Unlike other radiopharmaceuticals, it is not practical to produce PET radiopharmaceuticals at a central location for subsequent distribution to clinical and research facilities around the country. This limitation compels various academic and research facilities to manufacture their own PET radiopharmaceuticals for in-house use. For multiple reasons, 18 F fluorodeoxyglucose ([ 18 F]FDG) is one of the most commonly used radiopharmaceuticals. The synthesis of [ 18 F]FDG has been optimized and automated, thus allowing independent laboratories to produce this radiopharmaceutical safely. Nonetheless, these laboratories should acquire resources and expertise to fulfil ever increasing regulatory requirements for the safe production and usage of PET radiopharmaceuticals. In addition to [ 18 F]FDG, a wide array of new and novel radiotracers is being developed to explore various biological processes. This paper emphasizes the fact that it is possible to accomplish research and fulfil clinical needs within an academic setting with modest resources. A careful assessment of the need for due diligence in radiation safety issues is very important for the longevity of any PET research endeavour. (author)

Clinical Application of 18F-FDG PET in Alzheimer's Disease

International Nuclear Information System (INIS)

Ryu, Young Hoon

2008-01-01

PET of the cerebral metabolic rate of glucose is increasingly used to support the clinical diagnosis in the examination of patients with suspected major neurodegenerative disorders, such as Alzheimer's disease. 18 F-FDG PET has been reported to have high diagnostic performance, especially, very high sensitivity in the diagnosis and clinical assessment of therapeutic efficacy. According to clinical research data hitherto, 18 F-FDG PET is expected to be an effective diagnostic tool in early and differential diagnosis of Alzheimer's disease. Since 2004, Medicare covers 18 F-FDG PET scans for the differential diagnosis of fronto-temporal dementia (FTD) and Alzheimer's disease (AD) under specific requirements; or, its use in a CMS approved practical clinical trial focused on the utility of 18 F-FDG PET in the diagnosis or treatment of dementing neurodegenerative diseases

Synthesis, radiofluorination and first evaluation of [{sup 18}F]fluorophenylsulfonyl- and [{sup 18}F]fluorophenylsulfinyl-piperidines as serotonin 5-HT{sub 2A} receptor antagonists for PET

Energy Technology Data Exchange (ETDEWEB)

Muehlhausen, Ute; Sihver, Wiebke [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Ermert, Johannes, E-mail: j.ermert@fz-juelich.d [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Coenen, Heinz H. [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany)

2010-07-15

In psychiatric disorders, 5-HT{sub 2A} receptors play an important role. In order to study these receptors in vivo by positron emission tomography (PET), there is an increasing interest for subtype selective and high affinity radioligands. Up to now, no optimal radiotracer is available. Thus, 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfonyl)piperidine (9), possessing high affinity and sufficient subtype selectivity for 5-HT{sub 2A} receptors, and 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfinyl)piperidine (15) have been {sup 18}F-labelled by a nucleophilic one-step reaction. Both radiotracers could be prepared and isolated within 45 min, [{sup 18}F]9 in a radiochemical yield (RCY) of 34.5{+-}8% and [{sup 18}F]15 of 9.5{+-}2.5%. The K{sub i} values of 9 and 15 at 5-HT{sub 2A} receptors towards [{sup 3}H]ketanserin were determined to be 1.9{+-}0.6 and 198{+-}8 nM, respectively. Autoradiography with [{sup 18}F]9 and [{sup 18}F]15 on rat brain sections showed a very high nonspecific binding of >80% for [{sup 18}F]9 and 30% to 40% nonspecific binding for [{sup 18}F]15; however, it is still too high in order to compensate for its lower affinity. Even though the affinity of 9 is more promising compared with 15, the high nonspecific binding of both radiofluorinated tracers in rat brain does not recommend those as an in vivo PET imaging agent for serotonin 5-HT{sub 2A} receptors in humans.

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

Science.gov (United States)

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

2018-04-10

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

Characteristic of 18F-FDG Excretion According to Use Diuretics in 18F-FDG of PET/CT

International Nuclear Information System (INIS)

Jang, Dong Gun; Yang, Seoung Oh; Lee, Sang Ho; Bae, Jong Lim; Kim, Jeong Koo

2012-01-01

18 F-fluorodeoxyglucose ( 18 F-FDG) causes a significant amount of radioactivity retention in kidneys and urinary tract and degrades image quality and diagnostic performance. Diuretics are used to perform tests and prevent the urinary tract retention of 18 F-FDG. The purpose of the study is to investigate how the diuretics affect images and excretion rates of 18 F-FDG. The study consists of a group using diuretics for patients with no primary tumors or transfer lesions in kidneys according to PET/CT images, a group using physiological saline and the control group injecting only 18 F-FDG and SUVs are measured by configuring interested areas for each group. Also, SUVs are compared and evaluated depending on the lasix injection after basic inspection and injecting 18 F-FDG for quantitative analysis. The study shows that images with decreased background radioactivity and increased urine excretion due to using diuretics. However, an opposite result that there is no change in the amount of radioactivity in urine appears. The study concludes that the diuretics may decrease background radioactivity in the images but may not affect the 18 F-FDG excretion.

STM study of C60F18 high dipole moment molecules on Au(111)

Science.gov (United States)

Bairagi, K.; Bellec, A.; Chumakov, R. G.; Menshikov, K. A.; Lagoute, J.; Chacon, C.; Girard, Y.; Rousset, S.; Repain, V.; Lebedev, A. M.; Sukhanov, L. P.; Svechnikov, N. Yu.; Stankevich, V. G.

2015-11-01

Scanning tunneling microscopy and spectroscopy studies of C60F18 molecules deposited on Au(111) are reported and compared to C60 molecules both at liquid helium temperature and room temperature (RT). Whereas adsorption and electronic properties of C60F18 single molecules were studied at low temperature (LT), self-assemblies were investigated at RT. In both cases, the fluorine atoms of the C60F18 molecules are pointed towards the surface. Individual C60F18 molecules on Au(111) have a HOMO-LUMO gap of 2.9 eV. The self-assembled islands exhibit a close-packed hexagonal lattice with amorphous borders. The comparison with C60 molecules clearly demonstrates the influence of the C60F18 electric dipole moment (EDM) on the electronic properties of single molecules and on the thermodynamics of self-assembled islands. Besides, the apparent height value of a separate molecule increases in a self-assembly environment as a result of a depolarization phenomenon.

Nicotinic receptor imaging with F-18 A85380 PET in Alzheimer's disease and normal ageing

International Nuclear Information System (INIS)

Bottlaender, M.; Maziere, B.; Pappata, S.; Dolle, F.; Rowe, C.; Tochon-Danguy, H.; Reutens, D.; Chan, G.; Woodward, M.

2002-01-01

high affinity but low potency for the nicotinic receptor (i.e. it is a weak agonist). It is selective for the alpha2beta4 (A2B4) subtype. A85380 does not bind to the alpha 7 subtype receptor nor the ganglionic alpha3beta4 subtype and therefore has minimal cardiovascular effects. It also has low affinity for muscle nicotinic receptors (Sullivan JP 1996). These properties indicate a high level of safety when this compound is used in the extremely low (nanomolar) concentrations required for PET imaging studies. Labelling of A85380 with fluorine-18, a positron emitting radioisotope, has been achieved without alteration of the receptor binding characteristics by Frederic Dolle and colleagues at the CEA PET Centre, Orsay (Dolle F et al., 1998). In March 2000, F-18 A85380 PET studies in baboons were presented by Prof. Bernard Maziere at the France Australia Scientific Meeting in Melbourne. After this presentation a collaboration between the CEA PET Centre and ARMC was discussed between Prof. Maziere and Dr. Rowe (Director, Department of Nuclear Medicine and Centre for PET, ARMC). Subsequently in June 2000 at the US SNM meeting in St. Louis further discussions were held between Dr. Rowe and Professor Syrota. In September 2000, draft protocols were exchanged and communication between Frederic Dolle and Henri Tochon-Danguy commenced regarding the radiochemistry. In May 2001, Dr. Rowe visited the CEA PET Centre, Orsay and a collaborative agreement was signed. Subsequently between May and August 2001, CEA PET Centre supplied the chemical precursor, labelling method, toxicology results and human radiation dosimetry data to ARMC. The research plan is to investigate the uptake and distribution of F-18 A85380 with PET in normal elderly persons, and subjects with mild Alzheimer's disease, and to quantify the effect of age on uptake. We will assess the utility of nicotinic receptor imaging with PET for the early diagnosis of AD and its potential for monitoring therapies designed to

Syntheses of F-18 Labeled Fluoroalkyltyrosine Derivatives

International Nuclear Information System (INIS)

Moon, Byung Seok; Lee, Kyo Chul; Yang, Seung Dae; Chun, Kwon Soo; Chi, Dae Yoon

2005-01-01

Positron emission tomography (PET) offers the highest resolution of all nuclear medicine imaging modalities and allows quantitation of tracer concentration in tissues. For more than 60 years, some of C-11 or F-18 labeled amino acids have been synthesized and evaluated for potential use in oncology, neurology and psychiatric disorders. Besides, a variety of radioisotope labeled amino acids have proven to be useful for imaging tumors, especially for brain tumor, lung tumor and breast tumor. These amino acids can be subdivided into two categories. The first category is represented by radiolabled naturally occurring amino acids and structurally similar analogues. Although these radiolabeled amino acids have proven useful in detecting brain and systemic tumors, it is susceptible to in vivo metabolism through multiple pathways that give rise to numerous radiolabled metabolites. On the other side, structurally similar amino acid analogues have some significant advantages over the natural amino acids. These nonnatural amino acids are not metabolized, which simplifieds the kinetic analysis of their uptake. On the basis of the promising results obtained with these nonnatural amino acids in preclinical studies, recent efforts have focused on the development of new F-18 labeled nonnatural amino acids. Recently, O-(2-[ 18 F]Fluoroethyl)-L-tyrosine (FET), O-(3-[ 18 F]Fluoropropyl)-L-tyrosine (FPT) were developed and evaluated among structurally similar to a new amino acid analogue. FET has shown high uptake in activated inflammatory cells using an experimental acute abscess model and in inflammation within lymph nodes. FPT was superior to FDG and had a slight advantage over FET in the differentiation of tumor from inflammation, and, like FET, it appeared to be a potential amino acid tracer for tumor imaging with PET. In this paper, we elected to introduce fluoroethyl and fluoropropyl groups at the R 1 positions and OCH 3 at R 2 position to the same effect of FET. Herein, we wish

Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[18F]fluorocholine ([18F]dOC)

International Nuclear Information System (INIS)

Henriksen, G.; Herz, M.; Hauser, A.; Schwaiger, M.; Wester, H.-J.

2004-01-01

11 C-labeled choline ([ 11 C]CHO) and 18 F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[ 18 F]fluorocholine, ([ 18 F]dOC), a non-metabolizable [ 18 F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [ 18 F]dOC was compared with that of [ 11 C]choline ([ 11 C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [ 18 F]dOC and [ 11 C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC 50 [ 18 F]dOC= 11 μM; IC 50 [ 11 C]CHO=13 μM. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [ 18 F]dOC after 5 min incubation time is comparable to that of [ 11 C]CHO, whereas the uptake of [ 11 C]CHO was superior after 20 min incubation time. As for [ 11 C]CHO, kidney and liver were also the primary sites of uptake for [ 18 F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [ 18 F]dOC at 10 min post-injection, whereas [ 11 C]CHO uptake was higher at later time points. In conclusion, [ 18 F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [ 18 F]dOC and [ 11 C]CHO result in comparable cellular uptake levels at early time points. In contrast to [ 18 F]dOC, which is transported but not intracellularily trapped, the choline kinase substrate [ 11 C]CHO is transported

Do the metabolites of 6-[F-18]fluoro-L-dopa and of [F-18]fluoro-meta-L-tyrosine contribute to the F-18 accumulation in the human brain?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

The purpose of this study was to determine if the metabolites of 6-[F-18]fluoro-L-dopa (F-dopa) and of [F-18]fluoro-meta-L-tyrosine (FmLtyr) contribute to the accumulation of fluorine-18 in the brain through unspecific retention. PET studies were conducted on a healthy human subject who was treated with both of the radiopharmaceuticals and their labelled metabolites. Results indicated that in contrast to F-dopa, the metabolite of FmLtyr does not 'contaminate' the brain with extraneous fluorine-18

Fully automated synthesis of [(18) F]fluoro-dihydrotestosterone ([(18) F]FDHT) using the FlexLab module.

Science.gov (United States)

Ackermann, Uwe; Lewis, Jason S; Young, Kenneth; Morris, Michael J; Weickhardt, Andrew; Davis, Ian D; Scott, Andrew M

2016-08-01

Imaging of androgen receptor expression in prostate cancer using F-18 FDHT is becoming increasingly popular. With the radiolabelling precursor now commercially available, developing a fully automated synthesis of [(18) F] FDHT is important. We have fully automated the synthesis of F-18 FDHT using the iPhase FlexLab module using only commercially available components. Total synthesis time was 90 min, radiochemical yields were 25-33% (n = 11). Radiochemical purity of the final formulation was > 99% and specific activity was > 18.5 GBq/µmol for all batches. This method can be up-scaled as desired, thus making it possible to study multiple patients in a day. Furthermore, our procedure uses 4 mg of precursor only and is therefore cost-effective. The synthesis has now been validated at Austin Health and is currently used for [(18) F]FDHT studies in patients. We believe that this method can easily adapted by other modules to further widen the availability of [(18) F]FDHT. Copyright © 2016 John Wiley & Sons, Ltd.

Development of [18F]halofluorination and [18F]fluoride ion displacement reactions for the synthesis of F-18 labelled radiopharmaceuticals

International Nuclear Information System (INIS)

Chi, D.Y.

1986-01-01

Two fluorine-18 labeling methods, [ 18 F]halofluorination and [ 18 F]fluoride ion displacement reactions, have been developed to assess their potential for labeling molecules with the positron-emitting radionuclide fluorine-18 at the no-carrier-added level. Olefin halofluorination involves the in situ generation of a halogen-fluoride reagent and subsequent addition to an olefin. The characteristics of this reaction were investigated with three model olefins (allylbenzene, 1-hexene, and propene). A two-step method for the preparation of fluoroalkyl substituted amines and amides has been achieved. The sequence involves fluoride ion displacement of trifluoromethanesulfonates (triflates) from short-chain haloalkyl triflates, followed by fluoroalkylation of the amine or amide. Alternatively, short-chain fluoroalkyl halides can be prepared by halofluorination of a terminal olefin. These reactions have been used to prepare various fluoroalkyl derivatives of 1-phenylpiperazine and N-fluoroalkyl derivatives of the neuroleptic agent spiperone. A series of fluorine-18 labeled N-fluoroalkylated spiperone derivatives were synthesized by N-alkylation of spiperone with fluoroalkyl halides

The hemodynamic response of the alpha rhythm: an EEG/fMRI study.

NARCIS (Netherlands)

de Munck, J.C.; Goncalves, S.I.; Huijboom, L.; Kuijer, J.P.; Pouwels, P.J.; Heethaar, R.M.; Lopes da Silva, F.H.

2007-01-01

EEG was recorded during fMRI scanning of 16 normal controls in resting condition with eyes closed. Time variations of the occipital alpha band amplitudes were correlated to the fMRI signal variations to obtain insight into the hemodynamic correlates of the EEG alpha activity. Contrary to earlier

Preclinical incorporation dosimetry of (+)-[18F) flubatine in piglets

International Nuclear Information System (INIS)

Sattler, B.; Patt, M.; Sabri, O.; Kranz, M.; Donat, C.K.; Deuther-Conrad, W.; Fischer, S.; Brust, P.; Sattler, T.; Smits, R.; Hoepping, A.; Steinbach, J.

2015-01-01

Full text of publication follows. Aim: (+)-[ 18 F] flubatine is the mirror image isomer of (-)-[ 18 F] flubatine, which is successfully used for neuroimaging of alpha4beta2 nAChRs with PET. To assess the radiation risk by this new radiotracer, biodistribution, organ doses (OD) and the effective dose (ED) were investigated in a preclinical trials using piglets. Method: whole body dosimetry of (+)-[ 18 F] flubatine was performed in 3 female piglets (age: 43 ± 1.2 days, weight: 14 ± 1.0 kg). The animals were narcotized using 20 mg/kg Ketamine, 2 mg/kg Azaperone; 1.5% Isoflurane in 70% N 2 O/30% O 2 and sequentially PET-imaged up to 5 hours post i.v. injection of 183.5 ± 9.0 MBq on a SIEMENS Biograph16 PET/CT-system on 7 bed positions (BP) per frame, 1.5 to 6 min/BP, CT-attenuation correction (AC) and iterative reconstruction. All relevant organs were defined by volumes of interest. Exponential curves were fitted to the time-activity-data (%ID/g, and %ID/organ). Time- and mass-scales were adapted to the human order of magnitude. The ODs were calculated using the adult male model with OLINDA. The ED was calculated using tissue weighting factors as published in the ICRP103. Results: The highest OD was received by the urinary bladder (71.7 ± 26.3 μSv/MBq), the kidneys (45.1 ± 6.5 μSv/MBq) and the brain (32.3 ± 3.24 μSv/MBq). The highest contribution to the ED was by the urinary bladder (2.9 ± 1.1 μSv/MBq), the lungs (1.7 ± 0.02 μSv/MBq) and the red marrow (1.4 ± 0.1μSv/MBq). According to this data, the ED to humans is 14.3 ± 0.3 μSv/MBq. Conclusion: considering 40% underestimation of the ED to humans by preclinical dosimetry [1] the expected ED to humans after 300 MBq i.v. is 7.2 mSv, which is about the ED by (-)-[ 18 F]flubatine (6.8 mSv/300 MBq) and well within the range of what other 18 F-labeled compounds cause to humans. This risk assessment encourages to transfer (+)-[F 18 ] flubatine from preclinical to clinical study phases and to further develop

4- {sup 18}F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4- {sup 18}F]fluorophenol

Energy Technology Data Exchange (ETDEWEB)

Ludwig, Thomas; Ermert, Johannes E-mail: j.ermert@fz-juelich.de; Coenen, Heinz H

2002-02-01

This paper describes the improved synthesis of n.c.a. 4- {sup 18}F]fluorophenol for the preparation of {sup 18}F-labeled alkylarylethers. Nucleophilic fluorination of substituted benzophenone derivatives yielded n.c.a. 4- {sup 18}F]fluoro-4'-substituted benzophenones with 80- 90 % RCY, which were converted to benzoic acid phenylesters by treatment with peracetic acid. Strong electron-withdrawing substituents like nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration resulting in the formation of corresponding benzoic acid fluorophenylesters. N.c.a. {sup 18}F]fluorophenol is almost quantitatively formed after hydrolysis and can easily be converted with alkylhalides into n.c.a. {sup 18}F]fluoroarylalkylethers.

Preparation of highly specific radioactivity [{sup 18}F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Ryzhikov, Nikolaj N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Seneca, Nicholas [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD 20892 (United States); Krasikova, Raisa N. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gomzina, Natalia A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Shchukin, Evgeny [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Fedorova, Olga S. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Vassiliev, Dmitrij A. [Institute of Human Brain, Russian Academy of Science, 9, Pavlov str, 197376, Saint Petersburg (Russian Federation); Gulyas, Balazs [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, Hakan [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Savic, Ivanka [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Halldin, Christer [Department of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]. E-mail: christer.halldin@cns.ki.se

2005-02-01

A straightforward method for the preparation of no-carrier-added (n.c.a.) [{sup 18}F]flumazenil via standard nucleophilic radiofluorination of the corresponding nitro-analog Ro 15-2344 has been developed. The labeling was performed by employing the K{sup 18}F/kryptofix complex in DMF at 160 deg. C for 30 min and equimolar ratio [K/K2.2.2]{sup +18}F{sup -}/precursor. Under these conditions, an {sup 18}F incorporation rate into flumazenil was in the range of 55-60%. The final product was isolated by HPLC purification within a total synthesis time of 75 min and a radiochemical yield of about 30% (EOB). Human post-mortem whole-hemisphere autoradiography of brain sections demonstrated selective uptake of the radioligand in the areas of high density of the central benzodiazepine receptors (BZR). PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [{sup 18}F]flumazenil as for [{sup 11}C]flumazenil. In blocking experiments, almost all radioactivity was inhibited by the addition of unlabeled flumazenil. [{sup 18}F]Flumazenil is a suitable radioligand for PET assessment of the BZR.

Kinetics of 16-α-[18]fluoroestradiol-3,17-β-disulphatemate ([18F]FESDS) in piglet blood and brain

International Nuclear Information System (INIS)

Brust, P.; Roemer, J.; Fuechtner, F.; Kasch, H.; Steinbach, J.

2002-01-01

The suitability of [ 18 F]FESDS as PET tracer was investigated. After i.v. injection [ 18 F]FESDS was immediately trapped by the erythrocytes. The PET images did not allow the differentiation of brain regions because of the very high amounts retained in the blood. [ 18 F]FESDS is therefore not recommended for brain imaging with PET. (orig.)

{sup 18}F-Fluoroglucosylation of peptides, exemplified on cyclo(RGDfK)

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Hultsch, Christina; Schottelius, Margret; Auernheimer, Joerg; Alke, Andrea; Wester, Hans-Juergen [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany)

2009-09-15

Oxime formation between an aminooxy-functionalized peptide and an {sup 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 [{sup 18}F]fluorodeoxyglucose ([{sup 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 [{sup 18}F]FDG from routine production ([{sup 18}F]FDGTUM) containing an excess of d-glucose did not allow the radiosynthesis of [{sup 18}F]FDG-RGD in activities >37 MBq in reasonable yield, rendering the direct use of clinical grade [{sup 18}F]FDG for the routine clinical synthesis of {sup 18}F-labelled peptides impossible. Using no-carrier-added (n.c.a.) [{sup 18}F]FDG obtained via HPLC separation of [{sup 18}F]FDGTUM from excess glucose, however, afforded [{sup 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 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, [{sup 18}F]FDG-RGD showed increased tumour accumulation compared to the ''gold standard'' [{sup 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 {sup 18}F-labelling of aminooxy-functionalized peptides using n.c.a. [{sup 18}F]FDG represents a radiofluorination/glycosylation strategy that allows preparation of {sup 18}F-labelled peptides in high yield with suitable pharmacokinetics. As soon as the necessary n.c.a. preparation of [{sup 18}F]FDG prior to reaction with the Aoa-peptide can be implemented in a fully automated [{sup 18}F]FDG-synthesis, [{sup 18}F

Fast and repetitive in-capillary production of [18F]FDG

International Nuclear Information System (INIS)

Wester, Hans-Juergen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-01-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 μm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [ 18 F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, μ-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the 18 F-labelled intermediate followed by on-line formulation of [ 18 F]FDG. In-capillary 18 F-fluorination of 2.1 μmol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [ 18 F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 C resulted in a radiochemical yield of 88 ± 4% within 18 F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN 18 F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that similar or nearly identical procedures, and thus instrumentation, will allow ICR of other 18 F-labelled radiopharmaceuticals. (orig.)

Biodistribution and radiation dosimetry of [18F]-5-fluorouracil

International Nuclear Information System (INIS)

Hino-Shishikura, Ayako; Suzuki, Akiko; Minamimoto, Ryogo; Shizukuishi, Kazuya; Oka, Takashi; Tateishi, Ukihide; Sugae, Sadatoshi; Ichikawa, Yasushi; Horiuchi, Choichi; Inoue, Tomio

2013-01-01

Purpose: To estimate the radiation dose and biodistribution of 18 F-5-fluorouracil ([ 18 F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. Methods: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2 h after intravenous administration of [ 18 F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [ 18 F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. Results: In human subjects, high [ 18 F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [ 18 F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [ 18 F]-5-FU dose was higher in humans (0.0124 mSv/MBq) than in mice (0.0058 mSv/MBq). Conclusion: Biodistribution and radiation dosimetry of [ 18 F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [ 18 F]-5-FU PET/CT for human studies. - Highlights: ► The radiation dose and biodistribution of [ 18 F]-5-FU were estimated from mouse and human data. ► The biodistribution of [ 18 F]-5-FU of mouse and human was corresponded. ► Estimated absorbed radiation doses for organs

In vivo evaluation of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FEAU) as markers for suicide gene expression

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Alauddin, Mian M. [University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. T8.3895, P.O. Box 059, Houston, TX (United States); Shahinian, Antranic; Park, Ryan; Fissekis, John D.; Conti, Peter S. [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Tohme, Michel [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Department of Biomedical Engineering, UC Davis, Davis, CA (United States)

2007-06-15

FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [{sup 14}C]FIAU and [{sup 3}H]FEAU. PET imaging was performed using [{sup 18}F]FIAU and [{sup 18}F]FEAU. In vitro uptake of [{sup 14}C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p < 0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [{sup 3}H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p < 0.001) than in wild type cells at the same time points. In vivo uptake of [{sup 14}C]FIAU at 2 h in HSV1-tk positive tumors was 15.48 {+-} 3.94, 6.7-fold higher (p < 0.001) than in wild type tumors. Uptake of [{sup 3}H]FEAU in transduced tumors was 9.98 {+-} 1.99, 5.0-fold higher (p < 0.001) than in wild type tumors. Micro-PET images using [{sup 18}F]FIAU and [{sup 18}F]FEAU also showed very high uptake in HSV-tk tumors. [{sup 18}F]FIAU and [{sup 18}F]FEAU appear to be potential PET imaging agents for gene expression. (orig.)

Production And Quality Control Of Radiopharmaceutical 18F-FDG

International Nuclear Information System (INIS)

Dinh Thi Bich Lieu; Nguyen Van Si; Vu Van Tien

2011-01-01

18 F-FDG is a radiopharmaceutical for imaging diagnosis with PET/CT in Nuclear Medicine. Criteria of injection pharmaceuticals are the highest standards. So, quality assurance and quality control must be followed very strictly. The selection of the procedure for 18 F-FDG has based on several criteria: high chemical efficiency, short synthesis time, toxic component free and etc. The quality control of 18 F-FDG consist many fields such as: nuclear physic (nuclear purity), radiochemistry (radionuclear purity, radiochemical purity), chemistry (chemical purity), radiation measurement (half life), microbiology (pyrogen, endotoxin), etc. which is following USP, BP or EP. (author)

[18F] FDG PET in gastric non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Rodriguez, M.; Ahlstroem, H.; Sundin, A.; Rehn, S.; Hagberg, H.; Glimelius, B.; Sundstroem, C.

1997-01-01

The possibility of using [ 18 F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [ 18 F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [ 18 F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [ 18 F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [ 18 F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy. (orig.)

A novel facile method of labeling octreotide with (18)F-fluorine.

Science.gov (United States)

Laverman, Peter; McBride, William J; Sharkey, Robert M; Eek, Annemarie; Joosten, Lieke; Oyen, Wim J G; Goldenberg, David M; Boerman, Otto C

2010-03-01

Several methods have been developed to label peptides with (18)F. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH(+) 1305) [IMP466]) with (18)F. Octreotide was conjugated with the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In addition, small-animal PET/CT images were acquired. IMP466 was labeled with Al(18)F in a single step with 50% yield. The labeled product was purified by high-performance liquid chromatography to remove unbound Al(18)F and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4 h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N-morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer. The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar to that of (18)F-IMP466. (18)F

Evaluation of 19 cases of benign lesions with high accumulation of tracer on 18F-FDG PET imaging

International Nuclear Information System (INIS)

Wang Quanshi; Wu Hubing; Wang Mingfang; Huang Zuhan

2003-01-01

Objective: To review PET images of benign lesions with high accumulation of 18 F-FDG and to analyse the possibility of FDG PET imaging for differentiating the benign from the malignant. Methods: 18 F-FDG PET imaging was performed on 19 patients with benign diseases including 13 cases of active tuberculosis and 6 cases of other benign diseases. Positive pathologic or bacteriological results were obtained for all the patients. PET images were evaluated with standardized uptake value (SUV), lesion shapes , and radioactivity distribution. CT or MRI and histopathologic findings also were reviewed. Results: 1) Thirteen patients with active tuberculosis showed high uptake of 18 F-FDG. The SUV was 3.1±1.8. But radioactivity distribution in some lesions was not uniform and there were defect areas in the lesions. Histopathologic findings proved that the defect areas were induced by caseous necrosis. Seven cases of pulmonary tuberculosis showed two or multiple stripe and funicular high accumulation and other lesions displayed high uptake in sheet or irregular shape; 1 case of scrofula and 1 case of splenetic tuberculosis showed defect areas in the lesions; the other scrofula case showed focal intense uptake. Two of lumbar tuberculosis showed intense uptake in the lumbar vertebra, and one of the two cases complicated with the cold abscess showed bilateral high accumulation in the shape of sheet along musculus psoas major. In the peritoneal tuberculosis case, PET images showed diffuse incrassation and intense uptake in peritoneum and mesentery. CT findings revealed that the peritoneum and mesentery thickened. 2) Pulmonary abscess, pulmonary cryptococcus granuloma, cerebral cryptococcus granuloma, pulmonary inflammatory pseudotumor, leiomyoma, and breast adenoma all showed high accumulation in the shapes of nodule or mass. Mean SUV was 4.5±3.1. CT or MRI findings were the same as on PET images shape. Histopathologic work-up did not find necrosis in the lesions. Conclusions

Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.

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Ning Guo

Full Text Available With favorable pharmacokinetics and binding affinity for α(vβ(3 integrin, (18F-labeled dimeric cyclic RGD peptide ([(18F]FPPRGD2 has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18F-fluoride-aluminum complex labeled RGD tracer ([(18F]AlF-NOTA-PRGD2, provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(vβ(3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18F]FPPRGD2, [(18F]AlF-NOTA-PRGD2, and [(68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND = k(3/k(4 in tumor voxels. [(18F]AlF-NOTA-PRGD2 showed comparable Bp(ND value (3.75±0.65 with those of [(18F]FPPRGD2 (3.39±0.84 and [(68Ga]Ga-NOTA-PRGD2 (3.09±0.21 (p>0.05. Little difference was found in volume of distribution (V(T among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [(18F]AlF-NOTA-PRGD2 and [(68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images and clearance pattern, the actual specific binding component extrapolated from kinetic

Measurement of the 19F(n,2n)18F cross section from 18 to 27 MeV

International Nuclear Information System (INIS)

Hartmann, C.L.; DeLuca, P.M. Jr.

1990-01-01

the 19 F(n,2n) 18 F cross section was measured at neutron energies of 18, 21, 23, and 27 MeV. Nearly monoenergetic neutrons bombarded teflon (CF 2 ), Zr, and Au samples. 19 F(n,2n) 18 F cross section values were determined relative to nat Zr(n,xn) 89 Zr and 197 Au(n,2n) 196 Au from measurements of the 18 F, 89 Zr, and 196 Au activities. Our results are in agreement with previous measurements below 20 MeV and extend the usefulness of this reaction to 27 MeV. 22 refs., 1 fig., 2 tabs

Automated Synthesis of 18F-Fluoropropoxytryptophan for Amino Acid Transporter System Imaging

Directory of Open Access Journals (Sweden)

I-Hong Shih

2014-01-01

Full Text Available Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP to assess tryptophan transporters using an automated synthesizer. Methods. Tosylpropoxytryptophan (Ts-TP was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1 and HPLC (C-18 column, methanol : water = 7 : 3 analyses. In vitro cellular uptake of 18F-FTP and 18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with 18F-FTP and 18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv. Results. Radio-TLC and HPLC analyses of 18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected. Cellular uptake of 18F-FTP and 18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that 18F-FTP had less tumor uptake than 18F-FDG in prostate cancer model. However, 18F-FTP had more uptake than 18F-FDG in small cell lung cancer model. Conclusion. 18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by 18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

(18)F-nanobody for PET imaging of HER2 overexpressing tumors.

Science.gov (United States)

Xavier, Catarina; Blykers, Anneleen; Vaneycken, Ilse; D'Huyvetter, Matthias; Heemskerk, Jan; Lahoutte, Tony; Devoogdt, Nick; Caveliers, Vicky

2016-04-01

Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with (18)F and its validation for in vivo assessment of HER2 overexpression. The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models. [(18)F]FB-anti-HER2 nanobody was prepared with a 5-15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3h p.i.). [(18)F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. The GMP grade anti-HER2 nanobody was labeled with (18)F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation. Copyright © 2016 Elsevier Inc. All rights reserved.

18F-nanobody for PET imaging of HER2 overexpressing tumors

International Nuclear Information System (INIS)

Xavier, Catarina; Blykers, Anneleen; Vaneycken, Ilse; D'Huyvetter, Matthias; Heemskerk, Jan; Lahoutte, Tony; Devoogdt, Nick; Caveliers, Vicky

2016-01-01

Introduction: Radiolabeled nanobodies are exciting new probes for molecular imaging due to high affinity, high specificity and fast washout from the blood. Here we present the labeling of an anti-HER2 nanobody with 18 F and its validation for in vivo assessment of HER2 overexpression. Methods: The GMP grade anti-HER2 nanobody was labeled with the prosthetic group, N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]-SFB), and its biodistribution, tumor targeting and specificity were evaluated in mouse and rat tumor models. Results: [ 18 F]FB-anti-HER2 nanobody was prepared with a 5–15% global yield (decay corrected) and a specific activity of 24.7 ± 8.2 MBq/nmol. In vivo studies demonstrated a high specific uptake for HER2 positive xenografts (5.94 ± 1.17 and 3.74 ± 0.52%IA/g, 1 and 3 h p.i.) with high tumor-to-blood and tumor-to-muscle ratios generating high contrast PET imaging. The probe presented fast clearance through the kidneys (4%IA/g at 3 h p.i.). [ 18 F]FB-anti-HER2 nanobody is able to image HER2 expressing tumors when co-administered with the anti-HER2 therapeutic antibody trastuzumab (Herceptin), indicating the possibility of using the tracer in patients undergoing Herceptin therapy. Conclusions: The GMP grade anti-HER2 nanobody was labeled with 18 F. This new PET probe for imaging HER2 overexpression in tumors has ample potential for clinical translation.

Improved synthesis of 2'-deoxy-2'-[18F]-fluoro-1-β-D-arabinofuranosyl-5-iodouracil ([18F]-FIAU)

International Nuclear Information System (INIS)

Anderson, Harry; Pillarsetty, NagaVaraKishore; Cantorias, Melchor; Lewis, Jason S.

2010-01-01

An improved synthesis of 2'-[ 18 F]-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil ([ 18 F]-FIAU) has been developed. The method utilizes trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed coupling of 2-deoxy-2-[ 18 F]-fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose with 2,4-bis(trimethylsilyloxy)-5-iodouracil to yield the protected dibenzoyl-[ 18 F]-FIAU. Dibenzoyl-[ 18 F]-FIAU was deprotected with sodium methoxide to yield a mixture of α- and β-anomers in a ratio of 1:1, which were purified by HPLC. The procedure described in this article eliminates the need for HBr activation of the sugar prior to coupling with silylated iodouracil and is suitable for automation. The total reaction time was about 110 min, starting from [ 18 F]-fluoride. The average isolated yield of the required β-anomer was 10±6% (decay corrected) with average specific activity of 125 mCi/μmol.

Syntheses of F-18 Labeled Fluoroalkyltyrosine Derivatives

Energy Technology Data Exchange (ETDEWEB)

Moon, Byung Seok; Lee, Kyo Chul; Yang, Seung Dae; Chun, Kwon Soo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chi, Dae Yoon [Inha Univ., Inchon (Korea, Republic of)

2005-07-01

Positron emission tomography (PET) offers the highest resolution of all nuclear medicine imaging modalities and allows quantitation of tracer concentration in tissues. For more than 60 years, some of C-11 or F-18 labeled amino acids have been synthesized and evaluated for potential use in oncology, neurology and psychiatric disorders. Besides, a variety of radioisotope labeled amino acids have proven to be useful for imaging tumors, especially for brain tumor, lung tumor and breast tumor. These amino acids can be subdivided into two categories. The first category is represented by radiolabled naturally occurring amino acids and structurally similar analogues. Although these radiolabeled amino acids have proven useful in detecting brain and systemic tumors, it is susceptible to in vivo metabolism through multiple pathways that give rise to numerous radiolabled metabolites. On the other side, structurally similar amino acid analogues have some significant advantages over the natural amino acids. These nonnatural amino acids are not metabolized, which simplifieds the kinetic analysis of their uptake. On the basis of the promising results obtained with these nonnatural amino acids in preclinical studies, recent efforts have focused on the development of new F-18 labeled nonnatural amino acids. Recently, O-(2-[{sup 18}F]Fluoroethyl)-L-tyrosine (FET), O-(3-[{sup 18}F]Fluoropropyl)-L-tyrosine (FPT) were developed and evaluated among structurally similar to a new amino acid analogue. FET has shown high uptake in activated inflammatory cells using an experimental acute abscess model and in inflammation within lymph nodes. FPT was superior to FDG and had a slight advantage over FET in the differentiation of tumor from inflammation, and, like FET, it appeared to be a potential amino acid tracer for tumor imaging with PET. In this paper, we elected to introduce fluoroethyl and fluoropropyl groups at the R{sub 1} positions and OCH{sub 3} at R{sub 2} position to the same effect

18F-fluorination by crown ether-metal fluoride

International Nuclear Information System (INIS)

Irie, T.; Fukushi, K.; Ido, T.; Kasida, Y.; Nozaki, T.

1984-01-01

For non-carrier-added 18 F-labeling of organic compounds, details were studied concerning the previously developed KF-crown ether method. In the modified method, a minute amount of KOH instead of carrier KF is added for the preparation of the anhydrous 18 F from aqueous carrier-free 18 F. The following factors were examined in order to determine optimum conditions for the preparation of the anhydrous non-carrier-added 18 F and the labeling synthesis with it: effects of the vessel on the evaporation of the 18 F-KOH solution and the amount of added KOH for the conversion of aqueous 18 F to anhydrous 18 F, the solubilized activity of the 18 F obtained by the evaporation in organic solutions containing 18-Crown-6 and the labeling reaction, as exemplified by the synthesis of 21-fluoroprogesterone. (author)

Preparation and evaluation of ethyl [18F]fluoroacetate as a proradiotracer of [18F]fluoroacetate for the measurement of glial metabolism by PET

International Nuclear Information System (INIS)

Mori, Tetsuya; Sun, Li-Quan; Kobayashi, Masato; Kiyono, Yasushi; Okazawa, Hidehiko; Furukawa, Takako; Kawashima, Hidekazu; Welch, Michael J.; Fujibayashi, Yasuhisa

2009-01-01

Introduction: Changes in glial metabolism in brain ischemia, Alzheimer's disease, depression, schizophrenia, epilepsy and manganese neurotoxicity have been reported in recent studies. Therefore, it is very important to measure glial metabolism in vivo for the elucidation and diagnosis of these diseases. Radiolabeled acetate is a good candidate for this purpose, but acetate has little uptake in the brain due to its low lipophilicity. We have designed a new proradiotracer, ethyl [ 18 F]fluoroacetate ([ 18 F]EFA), which is [ 18 F]fluoroacetate ([ 18 F]FA) esterified with ethanol, to increase the lipophilicity of fluoroacetate (FA), allowing the measurement of glial metabolism. Methods: The synthesis of [ 18 F]EFA was achieved using ethyl O-mesyl-glycolate as precursor. The blood-brain barrier permeability of ethyl [1- 14 C]fluoroacetate ([ 14 C]EFA) was estimated by a brain uptake index (BUI) method. Hydrolysis of [ 14 C]EFA in the brain was calculated by the fraction of radioactivity in lipophilic and water fractions of homogenized brain. Using the plasma of five animal species, the stability of [ 14 C]EFA was measured. Biodistribution studies of [ 18 F]EFA in ddY mice were carried out and compared with [ 18 F]FA. Positron emission tomography (PET) scanning using common marmosets was performed for 90 min postadministration. At 60 min postinjection of [ 18 F]EFA, metabolite studies were performed. Organs were dissected from the marmosets, and extracted metabolites were analyzed with a thin-layer chromatography method. Results: The synthesis of [ 18 F]EFA was accomplished in a short time (29 min) and with a reproducible radiochemical yield of 28.6±3.6% (decay corrected) and a high radiochemical purity of more than 95%. In the brain permeability study, the BUI of [ 14 C]EFA was 3.8 times higher than that of sodium [1- 14 C]fluoroacetate. [ 14 C]EFA was hydrolyzed rapidly in rat brains. In stability studies using the plasma of five animal species, [ 14 C]EFA was stable

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.

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

Ferjancic, P; Harmon, S; Jeraj, R [University of Wisconsin, Madison, WI (United States); Chen, S [1st Hospital of China Medical University, Shenyang, Liaoning (China); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia)

2016-06-15

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

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

Science.gov (United States)

Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

2016-03-01

Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[{sup 18}F]Fluor-L-DOPA; Zur Synthese radiofluorierter aromatischer Aminosaeuren mittels Isotopenaustausch am Beispiel von 6-[{sup 18}F]Fluor-L-DOPA

Energy Technology Data Exchange (ETDEWEB)

Wagner, F M

2008-06-15

In nuclear medical diagnosis, 6-[{sup 18}F]fluoro-L-3,4-dihydroxyphenylalanine (6-[{sup 18}F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[{sup 18}F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic {sup 18}F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of {sup 18}F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[{sup 18}F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic {sup 18}F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via {alpha},{beta}-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[{sup 18}F]fluoro-L-DOPA. Only a combination of the protecting groups

Nicotinic {alpha}4{beta}2 receptor imaging agents

Energy Technology Data Exchange (ETDEWEB)

Pichika, Rama [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Easwaramoorthy, Balasubramaniam [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Collins, Daphne [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Christian, Bradley T. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Shi, Bingzhi [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Narayanan, Tanjore K. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Potkin, Steven G. [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Mukherjee, Jogeshwar [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States)]. E-mail: j.mukherjee@uci.edu

2006-04-15

The {alpha}4{beta}2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using {sup 3}H-cytisine exhibited a K {sub i}=0.50 nM for the {alpha}4{beta}2 sites. The radiosynthesis of 2-{sup 18}F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ({sup 18}F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/{mu}mol. In vitro autoradiography in rat brain slices indicated selective binding of {sup 18}F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with {alpha}4{beta}2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for {sup 18}F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 {mu}M nicotine in these brain regions. Positron emission tomography imaging study of {sup 18}F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of {sup 18}F-nifene indicates promise as a PET imaging agent and thus needs further evaluation.

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

International Nuclear Information System (INIS)

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

2008-01-01

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 18 F-fluorodeoxyglucose ( 18 F-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 18 F-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 18 F-FDG PET/CT and AUS followed by SNB and/or ALN dissection (ALND). Using 18 F-FDG PET/CT, we studied both a visual assessment of 18 F-FDG uptake and standardized uptake value (SUV) for axillary staging. In a visual assessment of 18 F-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 18 F-FDG PET/CT and AUS to the axilla, the sensitivity, specificity, and accuracy were 64, 94, and 85%, respectively. If either 18 F-FDG PET uptake or AUS was positive in allixa, the probability of axillary metastasis was high; 50% (6 of 12) in 18 F-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 18 F-FDG PET/CT, candidates of SNB were more appropriately selected. The axillary 18 F-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 18 F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their limited sensitivities, the high radiation

THE RGB AND AGB STAR NUCLEOSYNTHESIS IN LIGHT OF THE RECENT {sup 17}O(p, {alpha}){sup 14}N AND {sup 18}O(p, {alpha}){sup 15}N REACTION-RATE DETERMINATIONS

Energy Technology Data Exchange (ETDEWEB)

Palmerini, S.; Sergi, M. L.; La Cognata, M.; Pizzone, R. G.; Spitaleri, C. [INFN-Laboratori Nazionali del Sud, Catania (Italy); Lamia, L. [Dipartimento di Fisica e Astronomia, Universita di Catania, Catania (Italy)

2013-02-20

In recent years, the Trojan Horse Method (THM) has been used to investigate the low-energy cross sections of proton-induced reactions on A = 17 and A = 18 oxygen isotopes, overcoming extrapolation procedures and enhancement effects due to electron screening. In particular, the strengths of the 20 keV and 65 keV resonances in the {sup 18}O(p, {alpha}){sup 15}N and {sup 17}O(p, {alpha}){sup 14}N reactions, respectively, have been extracted, as well as the contribution of the tail of the broad 656 keV resonance in the {sup 18}O(p, {alpha}){sup 15}N reaction inside the Gamow window. The strength of the 65 keV resonance in the {sup 17}O(p, {alpha}){sup 14}N reaction, measured by means of the THM, has been used to renormalize the corresponding resonance strength in the {sup 17}O + p radiative capture channel. As a result, more accurate reaction rates for the {sup 18}O(p, {alpha}){sup 15}N, {sup 17}O(p, {alpha}){sup 14}N, and {sup 17}O(p, {gamma}){sup 18}F processes have been deduced, devoid of systematic errors due to extrapolation or the electron screening effect. Such rates have been introduced into state-of-the-art red giant branch and asymptotic giant branch (AGB) models for proton-capture nucleosynthesis coupled with extra-mixing episodes. The predicted abundances have been compared with isotopic compositions provided by geochemical analysis of presolar grains. As a result, an improved agreement is found between the models and the isotopic mix of oxide grains of AGB origins, whose composition is the signature of low-temperature proton-capture nucleosynthesis. The low {sup 14}N/{sup 15}N found in SiC grains cannot be explained by the revised nuclear reaction rates and remains a serious problem that has not been satisfactorily addressed.

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

International Nuclear Information System (INIS)

McLarty, Kristin; Moran, Matthew D.; Scollard, Deborah A.; Chan, Conrad; Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit; McLaurin, JoAnne; Nitz, Mark; Houle, Sylvain; Wilson, Alan A.; Reilly, Raymond M.; Vasdev, Neil

2011-01-01

Introduction: The aim of the study was to evaluate the uptake of [ 18 F]-1-deoxy-1-fluoro-scyllo-inositol ([ 18 F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [ 18 F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [ 18 F]-scyllo-inositol and [ 18 F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [ 18 F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [ 18 F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [ 18 F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [ 18 F]-scyllo-inositol in inflammation was lower than [ 18 F]-FDG. While uptake of [ 18 F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [ 18 F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [ 18 F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [ 18 F]-FDG. The tumour-to-brain ratio of [ 18 F]-scyllo-inositol was also significantly higher than that of [ 18 F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

Aspects of the production of /sup 18/F-2-deoxy-2-fluoro-D-glucose via /sup 18/F/sub 2/ with a tandem Van de Graaf accelerator

Energy Technology Data Exchange (ETDEWEB)

Shaughnessy, W J; Gatley, S J; Hichwa, R D; Lieberman, L M; Nickles, R J [Wisconsin Univ., Madison (USA). Dept. of Radiology

1981-01-01

During deuteron irradiation of 100 psig neon containing 1-2% of elemental fluorine, the induced /sup 18/F partitions into three main fractions. About 50% remains in the passivated nickel target after elution of the gas mixture. Some of the gaseous /sup 18/F is capable of performing fluorination reactions and is presumed to be /sup 18/F/sub 2/: the rest is a mixture of at least two unreactive gases, one of which behaves on gas chromatography like CF/sub 4/. The ratio of reactive to unreactive gaseous /sup 18/F decreases with longer irradiation times but increases when the target gas is cooled to -30C during bombardment. Reaction of the presumed /sup 18/F/sub 2/ with 4.5,6-triacetyl-D-glucal, essentially by the published method, yielded /sup 18/F-2-deoxy-2-fluoro-4,5,6-triacetyl-x-D-glucosyl fluoride and the corresponding ..beta..-D-mannosyl fluoride. These were separated either by column chromatography or preparative TLC, using plates with a pre-absorbent layer. Hydrolysis of the glucoyl fluoride gave /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/F-2FDG) with a decay-corrected yield of about 10% based on /sup 18/F trapped by the triacetylglucal. The 60 min organ distribution of /sup 18/F from /sup 18/F-2-FDG in tumor bearing rats was compared with the corresponding distribution after administration of /sup 18/F-3-deoxy-3-fluoro-D-glucose (/sup 18/F-3FDG). Organ/blood ratios were uniformly higher for /sup 18/F-2FDG than for no carrier added /sup 18/F-3FDG; only heart, brain and thyroid had ratios greater than unity. Added carrier 3-FDG further lowered organ/blood ratios. The main conclusion drawn from this animal work is that /sup 18/F-3FDG is unlikely to rival /sup 18/F-2FDG for nuclear medicine studies, where high target /blood ratios (obtained by metabolic trapping as the sugar-6-phosphate) are necessary. However /sup 18/F-3FDG may be useful for estimating the concentration of free glucose in organs if further work confirms that it is an essentially non

Comparative assessment of 6-[18 F]fluoro-L-m-tyrosine and 6-[18 F]fluoro-L-dopa to evaluate dopaminergic presynaptic integrity in a Parkinson's disease rat model.

Science.gov (United States)

Becker, Guillaume; Bahri, Mohamed Ali; Michel, Anne; Hustadt, Fabian; Garraux, Gaëtan; Luxen, André; Lemaire, Christian; Plenevaux, Alain

2017-05-01

Because of the progressive loss of nigro-striatal dopaminergic terminals in Parkinson's disease (PD), in vivo quantitative imaging of dopamine (DA) containing neurons in animal models of PD is of critical importance in the preclinical evaluation of highly awaited disease-modifying therapies. Among existing methods, the high sensitivity of positron emission tomography (PET) is attractive to achieve that goal. The aim of this study was to perform a quantitative comparison of brain images obtained in 6-hydroxydopamine (6-OHDA) lesioned rats using two dopaminergic PET radiotracers, namely [ 18 F]fluoro-3,4-dihydroxyphenyl-L-alanine ([ 18 F]FDOPA) and 6-[ 18 F]fluoro-L-m-tyrosine ([ 18 F]FMT). Because the imaging signal is theoretically less contaminated by metabolites, we hypothesized that the latter would show stronger relationship with behavioural and post-mortem measures of striatal dopaminergic deficiency. We used a within-subject design to measure striatal [ 18 F]FMT and [ 18 F]FDOPA uptake in eight partially lesioned, eight fully lesioned and ten sham-treated rats. Animals were pretreated with an L-aromatic amino acid decarboxylase inhibitor. A catechol-O-methyl transferase inhibitor was also given before [ 18 F]FDOPA PET. Quantitative estimates of striatal uptake were computed using conventional graphical Patlak method. Striatal dopaminergic deficiencies were measured with apomorphine-induced rotations and post-mortem striatal DA content. We observed a strong relationship between [ 18 F]FMT and [ 18 F]FDOPA estimates of decreased uptake in the denervated striatum using the tissue-derived uptake rate constant K c . However, only [ 18 F]FMT K c succeeded to discriminate between the partial and the full 6-OHDA lesion and correlated well with the post-mortem striatal DA content. This study indicates that the [ 18 F]FMT could be more sensitive, with respect of [ 18 F]FDOPA, to investigate DA terminals loss in 6-OHDA rats, and open the way to in vivo L

High radiochemical yield synthesis of [18F]FLT from 3'-O-nosylated thymidine and its 3-N-BOC-protected analogue

International Nuclear Information System (INIS)

Yoon, M. K.; Oh, S. J.; Ryu, J. S.; Moon, D. H.

2002-01-01

We synthesized 3'-O-nosylate and its 3-N-BOC-protected thymidine derivatives as two precursors for high radiochemical yield synthesis of [ 18 F]FLT and optimized [ 18 F]fluorination conditions. (5'-O-DMTr-2'-deoxy-3'-O-nosyl-β-D-threo-pentofuranosyl)thymidine and its s 3-N-BOD-protected analogue were prepared with 54% and 28% yield, respectively. After drying of [ 18 F]F-, 3'-O-nosylate(10-30 mg) or its 3-N-BOC-protected(11-34 mg) precursor was added to 500 μl of CH3CN, respectively. The mixtures were heated at 100-130 .deg. C for 5-30 min. For hydrolysis, 250-500 μl 1N HCl at 50 .deg. C for 5 min condition was used and 1.5ml of 2M sodium acetate was used for neutralization. Reaction mixture was purified by HPLC. The optimal [ 18 F]fluorination yield of 3'-O-nosylate precursor was 85±5.4% with 34 mg of precursor and a reaction time of 5 min at 130 .deg. C. For 3-N-BOC-protected analogue, [ 18 F]fluorination yield was 82±5.4% with 34 mg of precursor and a reaction time of 5 min at 110. deg. C. After HPLC purification, overall radiochemical yield using each precursors were 40±5.2% and 42±5.4% and radiochemical purity were 98±0.5% and 97±2.1% for two precursors, respectively. Preparation time was 60±10.5 min including HPLC purification for two precursors. From these two precursors, [ 18 F]FLT can be easily prepared with high radiochemical yield. 3-N-BOC-protected precursor required milder [ 18 F]fluorination conditions than 3'-O-nosylate precursor

A “dose on demand” Biomarker Generator for automated production of [18F]F− and [18F]FDG

International Nuclear Information System (INIS)

Awasthi, V.; Watson, J.; Gali, H.; Matlock, G.; McFarland, A.; Bailey, J.; Anzellotti, A.

2014-01-01

The University of Oklahoma—College of Pharmacy has installed the first Biomarker Generator (BG75) comprising a self-shielded 7.5-MeV proton beam positive ion cyclotron and an aseptic automated chemistry production and quality control module for production of [ 18 F]F − and clinical [ 18 F]FDG. Performance, reliability, and safety of the system for the production of “dose on demand” were tested over several months. No-carrier-added [ 18 F]F − was obtained through the 18 O(p,n) 18 F nuclear reaction by irradiation (20–40 min) of a >95% enriched [ 18 O]H 2 O target (280 μl) with a 7.5-MeV proton beam (3.5–5.0 μA). Automated quality control tests were performed on each dose. The HPLC-based analytical methods were validated against USP methods of quality control. [ 18 F]FDG produced by BG75 was tested in a mouse tumor model implanted with H441 human lung adenocarcinoma cells. After initial installment and optimization, the [ 18 F]F − production has been consistent since March 2011 with a maximum production of 400 to 450 mCi in a day. The average yield is 0.61 mCi/min and 0.92 mCi/min at 3.8 µA and 5 µA, respectively. The current target window has held up for over 25 weeks against >400 bombardment cycles. [ 18 F]FDG production has been consistent since June 2012 with an average of six doses/day in an automated synthesis mode (RCY≈50%). The release criteria included USP-specified limits for pH, residual solvents (acetonitrile/ethanol), kryptofix, radiochemical purity/identity, and filter integrity test. The entire automated operation generated minimal radiation exposure hazard to the operator and environment. As expected, [ 18 F]FDG produced by BG75 was found to delineate tumor volume in a mouse model of xenograft tumor. In summary, production and quality control of “[ 18 F]FDG dose on demand” have been accomplished in an automated and safe manner by the first Biomarker Generator. The implementation of a cGMP quality system is under way towards

Preparation and biological evaluation of 2-amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression

Energy Technology Data Exchange (ETDEWEB)

Cai Hancheng [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Yin Duanzhi [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)], E-mail: chcbati@yahoo.com.cn; Zhang Lan [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Yang, Xiaofeng; Xu Xiaoyan; Liu Weiguo; Zheng Xuesheng [Institute of Brain Medical Science, Second affiliated Hospital, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhang Hong [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Wang Jing [Department of Nuclear Medicine, Second Affiliated Hospital, Zhejiang University Medical PET Center, Medicine School of Zhejiang University, Hangzhou 310009 (China); Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Xu Yuhong [Zhejiang California International NanoSystems Institute, Hangzhou 310029 (China); Cheng Dengfeng; Zheng Mingqiang; Han Yanjiang; Wu Mingxing; Wang Yongxian [Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

2007-08-15

Introduction: 2-Amino-6-[{sup 18}F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[{sup 18}F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[{sup 18}F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[{sup 18}F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[{sup 18}F]FPCV was -0.517. 6-[{sup 18}F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[{sup 18}F]FPCV was as follows: {alpha} t{sub 1/2}=1.2 min and {beta} t{sub 1/2}=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[{sup 18}F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.

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

Science.gov (United States)

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

2014-01-01

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

The analysis of radiolysis impurities in 18F-FDG and methods of repurification

International Nuclear Information System (INIS)

Jinming Zhang; Yungang Li; Jian Liu; Xiaojun Zhang; Jiahe Tian

2010-01-01

To investigate the radio impurity in the radiolysis of 18 F-FDG at high radiodose and radioconcentrated solutions and develop methods of repurification. The radiolysis of 18 F-FDG was analyzed by TLC. The radio-impurity was confirmed by biodistribution and small animal PET/CT studies. 18 F-FDG was unstable at high radioconcentration over 37 GBq/mL or under basic condition. TLC, biodistribution and PET/CT all indicated that the main autoradiolysis byproduct was free fluoride ion. The radiolyzed 18 F-FDG was repurified by solid-phase extraction (SPE) column. The repurified 18 F-FDG had a radiochemical purity (RCP) of over 99% and significantly lower bone uptake than that was before repurification (P = 0.0003). There was a positive correlation between the recovery yield and the purity of 18 F-FDG (R 2 = 0.66). (author)

Ability of 18F-DOPA PET/CT and fused 18F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

International Nuclear Information System (INIS)

Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Puntoni, Matteo; Garre, Maria Luisa; Massollo, Michela; Naseri, Merhdad; Piccardo, Arnoldo; Lopci, Egesta

2016-01-01

To assess the diagnostic performance of 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with 18 F-DOPA PET/CT and brain MRI. Fused 18 F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for 18 F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for 18 F-DOPA PET/CT, respectively. 18 F-DOPA PET/MRI showed a trend towards higher accuracy compared with 18 F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with 18 F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and 18 F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of 18 F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the 18 F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by 18 F-DOPA PET/MRI. Physiological striatal 18 F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement. 18 F-DOPA PET/CT correctly detected

Targeting personalized medicine in a non-Hodgkin lymphoma patient with {sup 18F}-FDG and {sup 18F}-choline PET/CT

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Thalles H.; Filho, Raul S.; Castro, Ana Carolina G.; Paulino Junior, Eduardo; Mamede, Marcelo, E-mail: mamede.mm@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2017-02-15

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

Flight and full-scale wind-tunnel comparison of pressure distributions from an F-18 aircraft at high angles of attack. [Conducted in NASA Ames Research Center's 80 by 120 ft wind tunnel

Science.gov (United States)

Fisher, David F.; Lanser, Wendy R.

1994-01-01

Pressure distributions were obtained at nearly identical fuselage stations and wing chord butt lines in flight on the F-18 HARV at NASA Dryden Flight Research Center and in the NASA Ames Research Center's 80 by 120 ft wind tunnel on a full-scale F/A-18 aircraft. The static pressures were measured at the identical five stations on the forebody, three stations on the left and right leading-edge extensions, and three spanwise stations on the wing. Comparisons of the flight and wind-tunnel pressure distributions were made at alpha = 30 deg, 45 deg, and 60 deg/59 deg. In general, very good agreement was found. Minor differences were noted at the forebody at alpha = 45 deg and 60 deg in the magnitude of the vortex footprints and a Mach number effect was noted at the leading-edge extension at alpha = 30 deg. The inboard leading edge flap data from the wind tunnel at alpha = 59 deg showed a suction peak that did not appear in the flight data. This was the result of a vortex from the corner of the leading edge flap whose path was altered by the lack of an engine simulation in the wind tunnel.

18F-fluorination by crown ether-metal fluoride

International Nuclear Information System (INIS)

Irie, T.; Fukushi, K.; Ido, T.; Kasida, Y.; Nozaki, T.

1982-01-01

18 F-Fluorination by ''naked'' 18 F - anion produced by complexing anhydrous K 18 F, which was prepared from aqueous 18 F, with 18 -Crown-6 was described for preparing 18 F-21-fluoroprogesterone. In order to find out optimum conditions in this labelling method, various factors were investigated such as the solubility of KF in organic solvents containing 18 -Crown-6 and its reactivity for the nucleophilic displacement of 21-mesylate of progesterone. Chloroform was a good solvent in solubilization of KF and its reactivity. Problems in this labelling procedure were also examined, such as a supporter for transferring the labelled anhydrous K 18 F and reaction vessels. Use of a Teflon reaction vessel resulted in a good radiochemical yield based on the starting activity of $ 18 water. (author)

Tritium contamination in [18O] water containing 18F produced by a cyclotron

International Nuclear Information System (INIS)

Ito, S.; Saze, T.; Sakane, H.; Nishizawa, K.

2003-01-01

Tritium in the target [ 18 O] water irradiated with 9.6 MeV protons for producing [ 18 F] fluoride by 18 O(p, n) 18 F reaction was predicted from the consideration on the Q value of the 18 O(p, t) 16 O reaction. A tritium beta ray spectrum was measured by a liquid scintillation counter equipped with a multichannel analyzer. The ratio of the 3 H activity to the 18 F activity in the [ 18 O] target water was 2.4x10 -6 at the beam current of 25μA. Tritium also was detected in the [ 18 O] water for recycling and the wasted acetonitrile [ 18 O] water. The purified [ 18 F]-FDG solution was not contaminated by 3 H. The 40% 3 H out of the produced activity was lost in the course of the [ 18 F]-FDG synthesis. It was suggested that 3 H evaporated into the air during [ 18 F]-FDG synthesis and caused contamination of the workroom. The radiation workers should be prevented from environmental 3 H contamination. (author)

Vasculitis assessment with [{sup 18}F]F.D.G. positron emission tomography; Place de la tomographie par emission de positons (TEP) au [{sup 18}F]FDG dans l'exploration des vascularites

Energy Technology Data Exchange (ETDEWEB)

Liozon, E. [CHU Dupuytren, Services de Medecine Interne A, 87 - Limoges (France); Monteil, J. [CHU Dupuytren, Services de Medecine Nucleaire, 87 - Limoges (France)

2008-10-15

[{sup 18}F]fluorodeoxyglucose ({sup 18}F.D.G.) positron emission tomography (PET) is a noninvasive metabolic imaging modality that is well suited to the assessment of activity and extent of large vessel vasculitis, such as giant cell arteritis and Takayasu arteritis. PET could be more effective than magnetic resonance imaging in detecting the earliest stages of vascular wall inflammation. The visual grading of vascular [{sup 18}F]F.D.G. uptake makes it possible to discriminate arteritis from atherosclerosis, providing therefore high specificity. High sensitivity can be achieved provided scanning is performed during active inflammatory phase, preferably before starting corticosteroid treatment. Large scale prospective studies are needed to determine the exact value of PET imaging in assessing the large vessel vasculitis outcome and response to immunosuppressive treatment.

Radiosynthesis of [18F]FEt-Tyr-urea-Glu ([18F]FEtTUG) as a new PSMA ligand

International Nuclear Information System (INIS)

Al-Momani, E.; Malik, N.; Machulla, H.J.; Reske, S.N.; Solbach, C.

2013-01-01

An efficient radiosynthesis of [ 18 F]FEt-Tyr-urea-Glu ([ 18 F]FEtTUG) as a new ligand for prostate specific membrane antigen (PSMA) was developed by use of [ 18 F]fluoroethyltosylate as labeling precursor. The corresponding fluoroethyl-tyrosine-urea-glutamate peptide was prepared as reference standard for HPLC control and identified and characterized by standard procedures (MS, NMR). The labeling conditions were optimized with respect to reaction time, reaction temperature, base and solvent. The maximal radiochemical yield of [ 18 F]FEtTUG (77 ± 0.8 %) was obtained within a reaction time of 15 min at a reaction temperature of 80 deg C using 10 M NaOH (18 equiv. related to precursor) in 80 % aqueous acetonitrile. The total preparation time including radiosynthesis, hydrolysis, HPLC purification and formulation was 70 min (EOB). The radiochemical purity was ≥98 %. (author)

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

Science.gov (United States)

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

2018-05-10

Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18 F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18 F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18 F-FDG PET and 18 F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18 F-FDG PET and 18 F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUV max and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18 F-FDG PET and 18 F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE ( P = PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) ( P = 0.007, 0.028 respectively), with a trend toward improved survival ( P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18 F-NaF PET was associated with longer OS ( P = 0.027). Conclusion: Changes in 18 F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18 F-NaF PET was associated with OS, but was not useful for predicting TTP or tSRE in BD MBC

Fast and repetitive in-capillary production of [18F]FDG.

Science.gov (United States)

Wester, Hans-Jürgen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-04-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 microm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [(18)F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, micro-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the (18)F-labelled intermediate followed by on-line formulation of [(18)F]FDG. In-capillary(18)F-fluorination of 2.1 micromol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-D-mannopyranose (TATM; precursor for [(18)F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 degrees C resulted in a radiochemical yield of 88 +/- 4% within 97%, MeCN <5 microg/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [(18)F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that

Flight-Determined, Subsonic, Lateral-Directional Stability and Control Derivatives of the Thrust-Vectoring F-18 High Angle of Attack Research Vehicle (HARV), and Comparisons to the Basic F-18 and Predicted Derivatives

Science.gov (United States)

Iliff, Kenneth W.; Wang, Kon-Sheng Charles

1999-01-01

The subsonic, lateral-directional, stability and control derivatives of the thrust-vectoring F-1 8 High Angle of Attack Research Vehicle (HARV) are extracted from flight data using a maximum likelihood parameter identification technique. State noise is accounted for in the identification formulation and is used to model the uncommanded forcing functions caused by unsteady aerodynamics. Preprogrammed maneuvers provided independent control surface inputs, eliminating problems of identifiability related to correlations between the aircraft controls and states. The HARV derivatives are plotted as functions of angles of attack between 10deg and 70deg and compared to flight estimates from the basic F-18 aircraft and to predictions from ground and wind tunnel tests. Unlike maneuvers of the basic F-18 aircraft, the HARV maneuvers were very precise and repeatable, resulting in tightly clustered estimates with small uncertainty levels. Significant differences were found between flight and prediction; however, some of these differences may be attributed to differences in the range of sideslip or input amplitude over which a given derivative was evaluated, and to differences between the HARV external configuration and that of the basic F-18 aircraft, upon which most of the prediction was based. Some HARV derivative fairings have been adjusted using basic F-18 derivatives (with low uncertainties) to help account for differences in variable ranges and the lack of HARV maneuvers at certain angles of attack.

Fluorine-18 radiopharmaceuticals beyond [18F]FDG for use in oncology and neurosciences

International Nuclear Information System (INIS)

Coenen, H.H.; Elsinga, P.H.; Iwata, R.; Kilbourn, M.R.; Pillai, M.R.A.; Rajan, M.G.R.; Wagner, H.N.; Zaknun, J.J.

2010-01-01

Positron emission tomography (PET) is a rapidly expanding clinical modality worldwide thanks to the availability of compact medical cyclotrons and automated chemistry for the production of radiopharmaceuticals. There is an armamentarium of fluorine-18 ( 18 F) tracers that can be used for PET studies in the fields of oncology and neurosciences. However, most of the 18 F-tracers other than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) are in less than optimum human use and there is considerable scope to bring potentially useful 18 F-tracers to clinical investigation stage. The International Atomic Energy Agency (IAEA) convened a consultants' group meeting to review the current status of 18 F-based radiotracers and to suggest means for accelerating their use for diagnostic applications. The consultants reviewed the developments including the synthetic approaches for the preparation of 18 F-tracers for oncology and neurosciences. A selection of three groups of 18 F-tracers that are useful either in oncology or in neurosciences was done based on well-defined criteria such as application, lack of toxicity, availability of precursors and ease of synthesis. Based on the recommendations of the consultants' group meeting, IAEA started a coordinated research project on 'Development of 18 F radiopharmaceuticals (beyond [ 18 F]FDG) for use in oncology and neurosciences' in which 14 countries are participating in a 3-year collaborative program. The outcomes of the coordinated research project are expected to catalyze the wider application of several more 18 F-radiopharmaceuticals beyond FDG for diagnostic applications in oncology and neurosciences.

Characteristic of {sup 18}F-FDG Excretion According to Use Diuretics in {sup 18}F-FDG of PET/CT

Energy Technology Data Exchange (ETDEWEB)

Jang, Dong Gun; Yang, Seoung Oh; Lee, Sang Ho [Dept. of Nuclear Medicine, Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan (Korea, Republic of); Bae, Jong Lim [Dept. of Physics, Daegu University, Daegu (Korea, Republic of); Kim, Jeong Koo [Dept. of Radiological Science, Hanseo University, Seosan (Korea, Republic of)

2012-06-15

{sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) causes a significant amount of radioactivity retention in kidneys and urinary tract and degrades image quality and diagnostic performance. Diuretics are used to perform tests and prevent the urinary tract retention of {sup 18}F-FDG. The purpose of the study is to investigate how the diuretics affect images and excretion rates of {sup 18}F-FDG. The study consists of a group using diuretics for patients with no primary tumors or transfer lesions in kidneys according to PET/CT images, a group using physiological saline and the control group injecting only {sup 18}F-FDG and SUVs are measured by configuring interested areas for each group. Also, SUVs are compared and evaluated depending on the lasix injection after basic inspection and injecting {sup 18}F-FDG for quantitative analysis. The study shows that images with decreased background radioactivity and increased urine excretion due to using diuretics. However, an opposite result that there is no change in the amount of radioactivity in urine appears. The study concludes that the diuretics may decrease background radioactivity in the images but may not affect the {sup 18}F-FDG excretion.

Thermal 18F atom addition to olefins

International Nuclear Information System (INIS)

Rogers, P.J.M.

1986-01-01

The addition of thermal 18 F atoms to olefins was investigated using various substrate molecules. The 18 F atoms were produced by the 19 F(n,2n) 18 F nuclear reaction with >10 5 eV of energy which is removed by multiple collisions with SF 6 molecules before reaction occurs with an olefin. By varying the SF 6 /substrate mole ratio it was demonstrated that the fraction of non-thermal reactions is dependent upon the frequency of non-reactive energy reducing collisions with SF 6 . The rate constants for addition and abstraction reactions with propene, cis-1-chloropropene and trans-1-chloropropene were determined. The substitution of a C1 atom for the olefinic H atom in the C 1 position does not affect the rate of 18 F bond formation but it changes the orientation of attack. The 18 F atom prefers the terminal carbon-in propene and propene-d 6 by a factor of 1.35 while the preference is less than 0.5 for the terminal carbon in cis-1-chloropropene and trans-1-chloropropene. The addition of 18 F atoms to olefins creates vibrationally excited fluoroalkyl radicals which can either decompose or stabilize by collision with another molecule. The rate constants for decomposition of excited CH 3 CHCHC1F radicals formed by 18 F addition to cis-1-chloropropene and trans-1-chloropropene are competitive with C 1 -C 2 bond rotation. The 18 F atoms add to the parent molecule with retention of geometry and a memory of the geometry persists as demonstrated by the cis-1-fluoropropene/trans-1-fluoropropene decomposition product ratio

Association Between Osteogenesis and Inflammation During the Progression of Calcified Plaque Evaluated by 18F-Fluoride and 18F-FDG.

Science.gov (United States)

Li, Xiang; Heber, Daniel; Cal-Gonzalez, Jacobo; Karanikas, Georgios; Mayerhoefer, Marius E; Rasul, Sazan; Beitzke, Dietrich; Zhang, Xiaoli; Agis, Hermine; Mitterhauser, Markus; Wadsak, Wolfgang; Beyer, Thomas; Loewe, Christian; Hacker, Marcus

2017-06-01

18 F-FDG is the most widely validated PET tracer for the evaluation of atherosclerotic inflammation. Recently, 18 F-NaF has also been considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these 2 processes during disease progression. Methods: Thirty-four myeloma patients underwent 18 F-NaF and 18 F-FDG PET/CT examinations. Lesions were divided into 3 groups (noncalcified, mildly calcified, and severely calcified lesions) on the basis of calcium density as measured in Hounsfield units by CT. Tissue-to-background ratios were determined from PET for both tracers. The association between inflammation and osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least 2 examinations with both tracers. Results: There were significant correlations between the maximum tissue-to-background ratios of the 2 tracers (Spearman r = 0.5 [ P < 0.01]; Pearson r = 0.4 [ P < 0.01]) in the 221 lesions at baseline. The highest uptake of both tracers was observed in noncalcified lesions, but without any correlation between the tracers (Pearson r = 0.06; P = 0.76). Compared with noncalcified plaques, mildly calcified plaques showed concordant significantly lower accumulation, with good correlation between the tracers (Pearson r = 0.7; P < 0.01). In addition, enhanced osteogenesis-derived 18 F-NaF uptake and regressive inflammation-derived 18 F-FDG uptake were observed in severely calcified lesions (Pearson r = 0.4; P < 0.01). During follow-up, increased calcium density and increased mean 18 F-NaF uptake were observed, whereas mean 18 F-FDG uptake decreased. Most noncalcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of 18 F-NaF PET imaging and 18 F

Clinicopathological and prognostic relevance of uptake level using 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in primary breast cancer

International Nuclear Information System (INIS)

Ueda, Shigeto; Tsuda, Hitoshi; Asakawa, Hideki

2008-01-01

Using integrated 18 F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging ( 18 F-FDG PET/CT), the clinical significance of 18 F-FDG uptake was evaluated in patients with primary breast cancer. Clinicopathological correlation with the level of maximum standardized uptake values (SUV) 60 min obtained from preoperative 18 F-FDG PET/CT were examined in 152 patients with primary breast cancer. The prognostic impact of the level of SUV was explored using simulated prognosis derived from computed program Adjuvant! in 136 (89%) patients with invasive ductal carcinoma (IDC). High SUV level was significantly correlated with tumor invasive size (≤2 cm) (P 18 F-FDG would be predictive of poor prognosis in patients with primary breast cancer, and aggressive features of cancer cells in patients with early breast cancer. 18 F-FDG PET/CT could be a useful tool to pretherapeutically predict biological characteristics and baseline risk of breast cancer. (author)

Evaluation of factors influencing 18F-FET uptake in the brain

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Antoine Verger

2018-01-01

Full Text Available PET using the amino-acid O-(2-18F-fluoroethyl-l-tyrosine (18F-FET is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV and the tumour-to-brain ratio (TBR. The aim of this study was to explore physiological factors that might influence the relationship of SUV of 18F-FET uptake in various brain areas, and thus affect quantification of 18F-FET uptake in brain tumours. Negative 18F-FET PET scans of 107 subjects, showing an inconspicuous brain distribution of 18F-FET, were evaluated retrospectively. Whole-brain quantitative analysis with Statistical Parametric Mapping (SPM using parametric SUV PET images, and volumes of interest (VOIs analysis with fronto-parietal, temporal, occipital, and cerebellar SUV background areas were performed to study the effect of age, gender, height, weight, injected activity, body mass index (BMI, and body surface area (BSA. After multivariate analysis, female gender and high BMI were found to be two independent factors associated with increased SUV of 18F-FET uptake in the brain. In women, SUVmean of 18F-FET uptake in the brain was 23% higher than in men (p < 0.01. SUVmean of 18F-FET uptake in the brain was positively correlated with BMI (r = 0.29; p < 0.01. The influence of these factors on SUV of 18F-FET was similar in all brain areas. In conclusion, SUV of 18F-FET in the normal brain is influenced by gender and weakly by BMI, but changes are similar in all brain areas.

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

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Tamura Katsumi

2008-06-01

Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion The diagnostic accuracy of 18F-FDG PET/CT was shown to be nearly equal to ultrasound, and considering their

Evaluation of 18F-fluorothymidine positron emission tomography ([18F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer.

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Sharma, R; Mapelli, P; Hanna, G B; Goldin, R; Power, D; Al-Nahhas, A; Merchant, S; Ramaswami, R; Challapalli, A; Barwick, T; Aboagye, E O

2016-12-01

3'-Deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [ 18 F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy. Dynamic [ 18 F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [ 18 F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1. Ten patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [ 18 F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [ 18 F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response. The results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [ 18 F]FLT-PET/CT. However, [ 18 F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [ 18 F]FLT-PET/CT studies in this tumour type should be undertaken with caution.

Imaging of hypoxia in small animals with 18F fluoromisonidasole

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Kilian Krzysztof

2016-06-01

Full Text Available A method of automated synthesis of [18F]fluoromisonidazole ([18F]FMISO for application in preclinical studies on small animals was presented. A remote-controlled synthesizer Synthra RNplus was used for nucleophilic substitution of NITTP (1′-(2′-nitro-1-imidazolyl-2-O-tetrahydropyranyl-3-O-toluenesulfonyl-propanediol with 18F anion. Labeling of 5 mg of precursor was performed in anhydrous acetonitrile at 100°C for 10 min, and the hydrolysis with HCl was performed at 100°C for 5 min. Final purification was done with high-performance liquid chromatography (HPLC and the radiochemical purity of radiotracer was higher than 99%. Proposed [18F]FMISO synthesis was used as a reliable tool in studies on hypoxia in Lewis lung carcinoma (LLC in mouse models.

Microfluidic preparation of [18F]FE-SUPPY and [18F]FE-SUPPY:2 - comparison with conventional radiosyntheses

International Nuclear Information System (INIS)

Ungersboeck, Johanna; Philippe, Cecile; Mien, Leonhard-Key; Haeusler, Daniela; Shanab, Karem; Lanzenberger, Rupert; Spreitzer, Helmut; Keppler, Bernhard K.; Dudczak, Robert; Kletter, Kurt; Mitterhauser, Markus; Wadsak, Wolfgang

2011-01-01

Introduction: Recently, first applications of microfluidic principles for radiosyntheses of positron emission tomography compounds were presented, but direct comparisons with conventional methods were still missing. Therefore, our aims were (1) the set-up of a microfluidic procedure for the preparation of the recently developed adenosine A 3 -receptor tracers [ 18 F]FE-SUPPY [5-(2-[ 18 F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl) -6-phenylpyridine-5-carboxylate] and [ 18 F]FE-SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[ 18 F]fluoroethyl)sulfanylcarbonyl) -6-phenylpyridine-5-carboxylate] and (2) the direct comparison of reaction conditions and radiochemical yields of the no-carrier-added nucleophilic substitution with [ 18 F]fluoride between microfluidic and conventional methods. Methods: For the determination of optimal reaction conditions within an Advion NanoTek synthesizer, 5-50 μl of precursor and dried [ 18 F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (26 o C-180 o C) with defined reactant bolus flow rates (10-50 μl/min). Radiochemical incorporation yields (RCIYs) and overall radiochemical yields for large-scale preparations were compared with data from conventional batch-mode syntheses. Results: Optimal reaction parameters for the microfluidic set-up were determined as follows: 170 o C, 30-μl/min pump rate per reactant (reaction overall flow rate of 60 μl/min) and 5-mg/ml precursor concentration in the reaction mixture. Applying these optimized conditions, we observed a significant increase in RCIY from 88.2% to 94.1% (P 18 F]FE-SUPPY and that from 42.5% to 95.5% (P 18 F]FE-SUPPY:2 using microfluidic instead of conventional heating. Precursor consumption was decreased from 7.5 and 10 mg to 1 mg per large-scale synthesis for both title compounds, respectively. Conclusion: The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY

Preclinical evaluation of an {sup 18}F-trifluoroborate methionine derivative for glioma imaging

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Yang, Xiangyu [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China); National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Liu, Zhibo; Zhang, Huimin; Li, Zhu; Niu, Gang; Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Munasinghe, Jeeva P. [NIH, Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD (United States); Teng, Gaojun [Medical School of Southeast University, Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Nanjing (China)

2018-04-15

{sup 11}C-methionine (MET) is one of the most commonly used amino acid tracers for PET imaging of brain tumors. In this study, we report an {sup 18}F-labeled boron-derived methionine analogue, denoted as {sup 18}F-B-MET, as a potential substitute of {sup 11}C-MET for glioma PET imaging. {sup 19}F-B-MET was synthesized from readily available chemicals according to our previous publication. For kit development, {sup 19}F-B-MET was aliquoted in quantities of 10 nmol for on-demand one-step labeling. The {sup 18}F-labeling was performed by {sup 18}F-{sup 19}F isotope exchange, and quality control was performed by both HPLC and radio-TLC. Uptake of the tracer was determined in GL26, C6 and U87 tumor cells. PET imaging and the biodistribution assay were performed on mice bearing subcutaneous or orthotopic C6 and U87 tumor xenografts. Starting with 740-1110 MBq {sup 18}F-fluoride, >370 MBq of {sup 18}F-B-MET was obtained in 25 min (n = 5) with >99% purity and high specific activity (>37 GBq/μmol). {sup 18}F-B-MET demonstrated excellent in vitro stability with <1% decomposition after incubation with plasma for 2 h. In vitro cell uptake assay showed that {sup 18}F-B-MET accumulated in tumor cells in a time dependent manner and could be competitively inhibited by natural methionine and other L-type transporter transported amino acids. In vivo biodistribution and imaging studies showed high tumor accumulation (2.99 ± 0.23 %ID/g, n = 6) compared with low uptake of brain (0.262 ± 0.05 %ID/g, n = 6) at 60 min after injection in a subcutaneous C6 tumor model. Orthotropic C6 and U87 tumors were clearly visualized with high tumor to brain ratios at 60 min post-injection, corroborating with tumor L-type amino acid transporter 1 (LAT-1) expression levels. {sup 18}F-B-MET was radiolabeled with high yield in a one-step labeling process, showed excellent pharmacokinetic properties in vivo, with high tumor-to-brain contrast. (orig.)

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

International Nuclear Information System (INIS)

Hsu, W.K.; Feeley, B.T.; Krenek, L.; Stout, D.B.; Chatziioannou, A.F.; Lieberman, J.R.

2007-01-01

Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18 F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18 F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18 F-fluoride, and 18 F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18 F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18 F-FDG PET imaging at any time point. This study suggests that 18 F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

Science.gov (United States)

Hsu, W. K.; Feeley, B. T.; Krenek, L.; Stout, D. B.; Chatziioannou, A. F.; Lieberman, J. R.

2011-01-01

Purpose Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Methods Fractures were created in the femurs of immuno-competent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18F-fluoride, and 18F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. Results All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18F-FDG PET imaging at any time point. Conclusion This study suggests that 18F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point

F-18-FDG PET of the thyroid in Graves` disease; F-18-FDG-PET der Schilddruese bei Morbus Basedow

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Boerner, A.R.; Voth, E.; Schicha, H. [Klinik und Poliklinik fuer Nuklearmedizin, Koeln Univ. (Germany); Wienhard, K.; Wagner, R. [Max-Planck-Institut fuer Neurologische Forschung, Koeln (Germany)

1998-12-31

This study evaluates F-18-FDG PET of the thyroid in Graves` disease. Methods: Thirty patients were investigated the day before radioiodine therapy, 15 patients 3-10 days after radioiodine therapy. Twenty patients with cancer of the head or neck and normal thyroid function served as controls. Results: F-18-FDG uptake was higher in Graves` disease patients than in controls. Negative correlations of F-18-FDG uptake with half-life of radioiodine and absorbed radiation dose due to radioiodine therapy were found along with a positive correlation to autoantibody levels. Conclusion: Thus F-18-FDG PET is likely to give information on the biological activity of Graves` disease as well as on early radiation effects. (orig.) [Deutsch] Ziel: Diese Studie evaluiert F-18-Fluoro-Deoxy-Glukose (F-18-FDG) PET der Schilddruese bei Patienten mit M. Basedow. Methoden: 30 Patienten wurden am Tag vor Radioiod-Therapie, 15 Patienten am 3.-10. Tag nach Radioiodtherapie untersucht. 20 Patienten mit Kopf/Halstumoren und normaler Schilddruesenfunktion dienten als Kontrollgruppe. Ergebnisse: Die F-18-FDG-Aufnahme in der Schilddruese war signifikant hoeher bei Patienten mit M-Basedow im Vergleich zu den Kontrollen. Sie stieg mit hoeheren, antithyreoidalen Antikoerpern und sank bei laengerer I-131-Halbwertzeit. Es bestand eine Korrelation einer reduzierten Glukose-Utilisation bei hoeherer absorbierter Schilddruesendosis nach Radioiod-Therapie. Schlussfolgerung: Damit erscheint die F-18-FDG-PET-Untersuchung zur biologischen Aktivitaetsbeurteilung des M. Basedow und Darstellung von fruehen Strahleneffekten geeignet. (orig.)

4-[18F]Fluorophenylpiperazines by Improved Hartwig-Buchwald N-Arylation of 4-[18F]fluoroiodobenzene, Formed via Hypervalent λ3-Iodane Precursors: Application to Build-Up of the Dopamine D4 Ligand [18F]FAUC 316

Directory of Open Access Journals (Sweden)

Fabian Kügler

2014-12-01

Full Text Available Substituted phenylpiperazines are often neuropharmacologically active compounds and in many cases are essential pharmacophores of neuroligands for different receptors such as D2-like dopaminergic, serotoninergic and other receptors. Nucleophilic, no-carrier-added (n.c.a. 18F-labelling of these ligands in an aromatic position is desirable for studying receptors with in vivo molecular imaging. 1-(4-[18F]Fluorophenylpiperazine was synthesized in two reaction steps starting by 18F-labelling of a iodobenzene-iodonium precursor, followed by Pd-catalyzed N-arylation of the intermediate 4-[18F]fluoro-iodobenzene. Different palladium catalysts and solvents were tested with particular attention to the polar solvents dimethylformamide (DMF and dimethylsulfoxide (DMSO. Weak inorganic bases like potassium phosphate or cesium carbonate seem to be essential for the arylation step and lead to conversation rates above 70% in DMF which is comparable to those in typically used toluene. In DMSO even quantitative conversation was observed. Overall radiochemical yields of up to 40% and 60% in DMF and DMSO, respectively, were reached depending on the labelling yield of the first step. The fluorophenylpiperazine obtained was coupled in a third reaction step with 2-formyl-1H-indole-5-carbonitrile to yield the highly selective dopamine D4 ligand [18F]FAUC 316.

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.

Science.gov (United States)

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.

Intraoperative detection of ¹⁸F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria.

Science.gov (United States)

Povoski, Stephen P; Chapman, Gregg J; Murrey, Douglas A; Lee, Robert; Martin, Edward W; Hall, Nathan C

2013-03-04

Intraoperative detection of (18)F-FDG-avid tissue sites during 18F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of (18)F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. Of 58 patients undergoing (18)F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine (18)F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each (18)F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2-15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0-2.1) and 1.0 (± 0, range 1.0-1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three-sigma statistical

18F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis.

International Nuclear Information System (INIS)

Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C.

2008-01-01

Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68 Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ( 18 F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18 F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18 F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18 F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18 F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection

Longitudinal imaging of Alzheimer pathology using [{sup 11}C]PIB, [{sup 18}F]FDDNP and [{sup 18}F]FDG PET

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Ossenkoppele, Rik; Tolboom, Nelleke; Adriaanse, Sofie F. [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Foster-Dingley, Jessica C.; Boellaard, Ronald; Yaqub, Maqsood; Windhorst, Albert D.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Barkhof, Frederik [VU University Medical Center, Department of Radiology, Amsterdam (Netherlands); Scheltens, Philip [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Center, Department of Neurology and Alzheimer Center, PO Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands)

2012-06-15

[{sup 11}C]PIB and [{sup 18}F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [{sup 18}F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls. Longitudinal, paired, dynamic [{sup 11}C]PIB and [{sup 18}F]FDDNP (90 min each) and static [{sup 18}F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [{sup 11}C]PIB and [{sup 18}F]FDDNP images of binding potential (BP{sub ND}) and [{sup 18}F]FDG standardized uptake value ratio (SUVr) images were generated. A significant increase in global cortical [{sup 11}C]PIB BP{sub ND} was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [{sup 11}C]PIB BP{sub ND} in MCI patients was most prominent in the lateral temporal lobe (p < 0.05). For [{sup 18}F]FDDNP, no changes in global BP{sub ND} were found. [{sup 18}F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p < 0.01). Changes in global [{sup 11}C]PIB binding ({rho} = -0.42, p < 0.05) and posterior cingulate [{sup 18}F]FDG uptake ({rho} = 0.54, p < 0.01) were correlated with changes in Mini-Mental-State Examination score over time across groups, whilst changes in [{sup 18}F]FDDNP binding ({rho} = -0.18, p = 0.35) were not. [{sup 11}C]PIB and [{sup 18}F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [{sup 18}F]FDDNP seems to be less useful for examining disease progression. (orig.)

Direct comparison of [18F]MH.MZ and [18F]altanserin for 5-HT2A receptor imaging with PET

DEFF Research Database (Denmark)

Hansen, Hanne Demant; Ettrup, Anders; Herth, Matthias Manfred

2013-01-01

]altanserin was blocked by ketanserin supporting that both radioligands bind to 5-HT(2A) receptors in the pig brain. In the HPLC analysis of pig plasma, [(18) F]MH.MZ displayed a fast and reproducible metabolism resulting in hydrophilic radiometabolites only whereas the metabolic profile of [(18) F]altanserin as expected......]altanserin were investigated in Danish Landrace pigs by brain PET scanning at baseline and after i.v. administration of blocking doses of ketanserin. Full arterial input function and HPLC analysis allowed for tissue-compartment kinetic modelling of PET data. In vitro autoradiography showed high binding...

Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine

International Nuclear Information System (INIS)

Oh, Seung Jun; Mosdzianowski, Christoph; Chi, Dae Yoon; Kim, Jung Young; Kang, Se Hun; Ryu, Jin Sook; Yeo, Jeong Seok; Moon, Dae Hyuk

2004-01-01

We developed a new fully automated method for the synthesis of 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT), by modifying a commercial FDG synthesizer and its disposable fluid pathway. Optimal labeling condition was that 40 mg of precursor in acetonitrile (2 mL) was heated at 150 degree sign C for 100 sec, followed by heating at 85 degree sign C for 450 sec and hydrolysis with 1 N HCl at 105 degree sign C for 300 sec. Using 3.7 GBq of [ 18 F]F - as starting activity, [ 18 F]FLT was obtained with a yield of 50.5±5.2% (n=28, decay corrected) within 60.0±5.4 min including HPLC purification. With 37.0 GBq, we obtained 48.7±5.6% (n=10). The [ 18 F]FLT showed the good stability for 6 h. This new automated synthesis procedure combines high and reproducible yields with the benefits of a disposable cassette system

Enantioselective synthesis of 6-[18F] fluoro-L-DOPA

International Nuclear Information System (INIS)

Zhang Lan; Tang Ganghua; Zhou Wei; Li Junling; Yin Duanzhi; Wang Yongxian; Tang Xiaolan; Huang Zuhan

2002-01-01

Trimethylammonium veratraldehyde triflate was synthesized and used as a precurser for the synthesis of 6-[ 18 F] Fluoro-L-DOPA by using the chiral phase-transfer catalyst, O-Allyl-N-(9)-anthracenylcinchonidinium bromide which was also synthesized in this study. Based on these, 6-[ 18 F] Fluoro-L-DOPA was prepared with acceptable radiochemical yield (10 ± 3)% in short synthesis time (80 min), with high radiochemical purity, specific activity and chemical purity

Elevated 18F-NaF uptake in cricoid cartilage in a patient with laryngeal carcinoma

Science.gov (United States)

Xia, Yuxiao; Qi, Chi; Zhang, Shumao; Huang, Zhanwen; Chen, Yue

2017-01-01

Abstract Rationale: Laryngeal cancer is aggressive tumor that arises from the tissues of the larynx. Although any bone can be affected, involvement of cricoid cartilage was reported very rarely, and there has been no report of 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT) and 3D PET-CT for the evaluation of cricoid cartilage invasion. Patient concerns: A 54-year-old male discovered a protruding mass in the right anterior neck, which had rapidly increased in size over a period of 2 months. Subsequently, hoarseness, dysphagia, and dyspnea were gradually developed. Diagnoses: 18F-FDG PET-CT demonstrated that the abnormal activity was located in a soft tissue mass, which was about 4.2 cm × 3.8 cm × 3.6 cm in largest dimension in the laryngeal cavity of supraglottic portion (SUVmax: 23.6). A swollen lymph node was revealed in the right submandibular region, which had intense FDG activity with a SUVmax of 18.4. However, there is a high uptake of 18F-FDG in the region near the bone, which is uncertain whether there is any skeletal invasion. NaF PET-CT and 3D PET-CT demonstrated increased uptake in the right side of cricoid cartilage (SUVmax: 13.2). The histopathologic examination confirmed squamous cell carcinoma of larynx. Interventions: The patient underwent tracheotomy and received anti-infective treatment to relieve symptoms of dyspnea and prevent asphyxia. Outcomes: Clinical follow up of the patient revealed that dyspnea was significantly relieved. Lessons: The case report shows the imaging features of cricoid cartilage invasion, including 18F-FDG PET/CT, 18F-sodium fluoride positron emission tomography-computed tomography (18F-NaF PET-CT), and 3D PET-CT. Precise understanding of the invasion scope, accurately staging of laryngeal carcinoma, and choosing of the most suitable surgical scheme are the factors that lead to the optimal treatment of laryngeal neoplasms. PMID:29245332

First (18)F-labeled ligand for PET imaging of uPAR

DEFF Research Database (Denmark)

Persson, Morten; Liu, Hongguang; Madsen, Jacob

2013-01-01

Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA......-conjugated version (NOTA-AE105) for development of the first (18)F-labeled uPAR positron-emission-tomography PET ligand using the Al(18)F radiolabeling method. In this study, the potential of (18)F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated....

Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride

International Nuclear Information System (INIS)

Shen, B.; Ehrlichmann, W.; Uebele, M.; Machulla, H.-J.; Reischl, G.

2009-01-01

An improved, automated synthesis of [ 18 F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064±3076 MBq of [ 18 F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both ≥95%. Specific activity was ca. 50 GBq/μmol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [ 18 F]FDOPA.

Imaging dopamine-2 receptors in cebus apella at PET with F-18 fluoropropylspiperone and F-18 fluorinated benzamide neuroleptic

International Nuclear Information System (INIS)

Mukherjee, J.; Yasillo, N.J.; Luh, K.E.; Diamond, M.; Levy, D.; Chen, C.T.; Cooper, M.

1990-01-01

Tardive dyskinesia (TD), an intractable disorder believed to involve dysfunction of dopamine D-2 receptors, often occurs with neuroleptic treatment in neuropsychiatric illness. This paper investigates the role of these receptors using a unique primate model of TD with newly developed (F-18) fluorinated radioligands. Two radioligands, (F-18)FPMB (one of a new class of fluorinated benzamide neuroleptics) have been used to image these receptors in a normal Cebus apella. Either (F-18)FPSP or (F-18)FPMB was administered intravenously to a normal Cebus, which was scanned for 2 hours in a PETT VI tomograph

Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Energy Technology Data Exchange (ETDEWEB)

McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2011-10-15

Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

PET imaging of lung inflammation with [18F]FEDAC, a radioligand for translocator protein (18 kDa.

Directory of Open Access Journals (Sweden)

Akiko Hatori

Full Text Available PURPOSE: The translocator protein (18 kDa (TSPO is highly expressed on the bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi, pneumocytes and alveolar macrophages in human lung. This study aimed to perform positron emission tomography (PET imaging of lung inflammation with [(18F]FEDAC, a specific TSPO radioligand, and to determine cellular sources enriching TSPO expression in the lung. METHODS: An acute lung injury model was prepared by intratracheal administration of lipopolysaccharide (LPS to rat. Uptake of radioactivity in the rat lungs was measured with small-animal PET after injection of [(18F]FEDAC. Presence of TSPO was examined in the lung tissue using Western blot and immunohistochemical assays. RESULTS: The uptake of [(18F]FEDAC increased in the lung with the progress of inflammation by treatment with LPS. Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease in the lung uptake of [(18F]FEDAC due to competitive binding to TSPO. TSPO expression was elevated in the inflamed lung section and its level responded to the [(18F]FEDAC uptake and severity of inflammation. Increase of TSPO expression was mainly found in the neutrophils and macrophages of inflamed lungs. CONCLUSION: From this study we conclude that PET with [(18F]FEDAC may be a useful tool for imaging TSPO expression and evaluating progress of lung inflammation. Study on human lung using [(18F]FEDAC-PET is promising.

Routine production of 18F using 16.5 MeV cyclotron for synthesis of 2-(18F)fluro-2-deoxy-d-glucose (FDG)

International Nuclear Information System (INIS)

Abd Jalil Abd Hamid; Soni, P.S.; Rajan, M.G.R.

2006-01-01

A medium energy cyclotron with maximum of 75 mA beam current is capable of producing most common Positron Emission Tomography (PET) radionuclides in sufficient quantities. The cyclotron has two targets for production of Flourine-18. One is high yield target system (HYT) (1.2 mL) and the other is HYT Generation II (Gen-II) (2.2 mL) and capable of producing 110 and 170 GBq respectively. Enriched 18 O water (>95%) is used for the routine production of Flourine-18 using the 18 O(p,n) 18 F nuclear reaction and irradiated under helium gas pressurized at 59-65 kPa at a beam current of 35 mA - 55 mA for 20-67 minutes. The [ 18 F]fluoride ion produced are used for the synthesis of 2-fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG). Various factors that may effect the production of PET radionuclides and one such factor includes the silver target body often introduce impurity such as silver oxides in form of black particles that can impede the (ID 0.75 mm) delivery line. Such contaminants would reduce the quantity of the available useful radioisotopes, and hinder the subsequent radiopharmaceutical processes. Used of HYT and HYT Gen-II for the routine production of 18 F- in few ten GBq quantities were reported

Radiation dosimetry of [(18)F]VAT in nonhuman primates.

Science.gov (United States)

Karimi, Morvarid; Tu, Zhude; Yue, Xuyi; Zhang, Xiang; Jin, Hongjun; Perlmutter, Joel S; Laforest, Richard

2015-12-01

The objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (-)-(1-((2R,3R)-8-(2-[(18)F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([(18)F]VAT) based on PET imaging in nonhuman primates. [(18)F]VAT has potential for investigation of neurological disorders including Alzheimer's disease, Parkinson's disease, and dystonia. Three macaque fascicularis (two males, one female) received 185.4-198.3 MBq [(18)F]VAT prior to whole-body imaging in a MicroPET-F220 scanner. Time activity curves (TACs) were created from regions of interest (ROIs) that encompassed the entire small organs or samples with the highest activity within large organs. Organ residence times were calculated based on the TACs. We then used OLINDA/EXM 1.1 to calculate human radiation dose estimates based on scaled organ residence times. Measurements from directly sampled arterial blood yielded a residence time of 0.30 h in agreement with the residence time of 0.39 h calculated from a PET-generated time activity curve measured in the left ventricle. Organ dosimetry revealed the liver as the critical organ (51.1 and 65.4 μGy/MBq) and an effective dose of 16 and 19 μSv/MBq for male and female, respectively. The macaque biodistribution data showed high retention of [(18)F]VAT in the liver consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [(18)F]VAT can be administered to obtain imaging in humans.

The Semi-automatic Synthesis of 18F-fluoroethyl-choline by Domestic FDG Synthesizer

Directory of Open Access Journals (Sweden)

ZHOU Ming

2016-02-01

Full Text Available As an important complementary imaging agent for 18F-FDG, 18F-fluoroethyl-choline (18F-FECH has been demonstrated to be promising in brain and prostate cancer imaging. By using domestic PET-FDG-TI-I CPCU synthesizer, 18F-FECH was synthesized by different reagents and consumable supplies. The C18 column was added before the product collection bottle to remove K2.2.2. The 18F-FECH was synthesized by PET-FDG-IT-I synthesizer efficiently about 30 minutes by radiochemical yield of 42.0% (no decay corrected, n=5, and the radiochemical purity was still more than 99.0% after 6 hours. The results showed the domestic PET-FDG-IT-I synthesizer could semi-automatically synthesize injectable 18F-FECH in high efficiency and radiochemical purity

Characterization of 18F-dipicolylamine (DPA) derivatives in cells infected with influenza virus

International Nuclear Information System (INIS)

Li, Junling; Gerlach, Rachael L.; Jonsson, Colleen B.; Gray, Brian D.; Pak, Koon Y.; Ng, Chin K.

2015-01-01

Objective: Bis(Zn-dipicolylamine (Zn-DPA)) coordination complexes represent a new class of synthetic small molecules that can target anionic phosphatidylserine (PS) in the apoptotic cells with high affinity and specificity. In this study, we labeled Zn-DPA and Cy7-Zn-DPA with different 18 F-prosthetic groups and characterized their uptake in A549 cells infected with influenza A virus from the 2009 pandemic (H1N1pdm). Methods: DPA was labeled with N-succinimidyl 4- 18 F-fluorobenzoate ( 18 F-SFB), 4-nitrophenyl 2- 18 F-fluoropropionate ( 18 F-NFP), 2- 18 F-Fluoroethyl toslyate ( 18 F-FET), and 18 F-aluminum (Al 18 F), respectively. Cy7-DPA was labeled with 18 F-SFB and 18 F-NFP only. The tracers were reconstituted with zinc nitrate before use. Apoptosis in A549 cells was induced by infection with the H1N1pdm virus for 48 h. Three μCi of each tracer was added to each well and incubated at 37 °C. The effect of different prosthetic groups, different MOI, and incubation time on percent cellular uptake was studied. Cell internalization and efflux was evaluated within 2 h of incubation. The competitive binding assay was performed with increasing concentration (10 −12 -10 −5 M) of Zn-DPA or Cy7-Zn-DPA prior to the addition of either 18 F-FB-Zn-DPA or 18 F-FB-Cy7-Zn-DPA into each well. IC 50 values for the two Zn-DPA analogues were estimated by GraphPad Prism 6.0. Results: Among all the four prosthetic groups, the 18 F-SFB method provided the highest conjugation yield for DPA and the highest uptake ratio between the infection cells and the control when both Zn-DPA and Cy7-Zn-DPA were present in the complex. The uptake ratio was similar for 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA. Uptake of 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA was proportional to the degree of apoptosis with a plateau at MOI 3. Uptake of 18 F-FB-Cy7-Zn-DPA also increased over incubation time and reached a plateau at 1 h, whereas uptake of 18 F-FB-Zn-DPA did not show any significant change over time

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

International Nuclear Information System (INIS)

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

2010-01-01

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 radioactive

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

Science.gov (United States)

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

Synthesis and quality control of [18F] fluorothymidine

International Nuclear Information System (INIS)

Nascimento, Leonardo Tafas C.; Silva, Juliana B.; Silveira, Marina B.; Santos, Priscilla F.; Faria, Tiago

2013-01-01

The Positron Emission Tomography (PET) is a technique that allows early diagnosis of various diseases by detecting metabolic changes of cells, in addition to being a noninvasive technique. The most widely used radiopharmaceutical for PET imaging is [ 18 F] Fludesoxiglucose ( 18 FDG), which is a marker of glucose metabolism and has high sensitivity and specificity for diagnosis and staging of various cancers. However, some carcinomas do not have high glucose consumption, besides 18 FDG possess high urinary excretion rate interfering with the detection of tumors in pelvis and high uptake in brain and in inflammation, reducing the contrast tumor / background. The radiotracer 3'-fluoro-L-3'-deoxythymidine ( 18 FLT) is an analogue of thymidine used as an alternative to 18 FDG for detecting tumors with high proliferation rate. The aim of this work was to develop [ 18 F] Fluorothymidine synthesis and quality control at the Radiopharmaceuticals Research and Production Facility of CDTN/CNEN. The synthesis was adapted from that used to 18 FDG, based on the methodologies described in related papers. Radiochemical purity and impurities levels were determined by HPLC, RTLC and GC techniques. Total synthesis time was 35 minutes and the radiochemical yield in the end of bombardment (EOB) was 7%, with a radiochemical purity of about 93%. Radionuclidic identity and purity, pH, residual solvents, radiochemical and chemical purity were evaluated according to analytical methods described on the literature and on the United States Pharmacopeia (USP 32). Residual levels of Stavudine, Thymine and Thymidine were found and are under toxicological investigation in order to establish a maximum amount allowed in the final product. (author)

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

Science.gov (United States)

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

2015-06-01

It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (PPET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P0.05, respectively). One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Radiosynthesis and biological evaluation of 5-(3-[18F]Fluoropropyloxy)-L-tryptophan for tumor PET imaging

International Nuclear Information System (INIS)

He, Shanzhen; Tang, Ganghua; Hu, Kongzhen; Wang, Hongliang; Wang, Shuxia; Huang, Tingting; Liang, Xiang; Tang, Xiaolan

2013-01-01

Introduction: [ 18 F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[ 18 F]Fluoropropyloxy)-L-tryptophan ([ 18 F]-L-FPTP) by two-step reactions and performed its biologic evaluation. Methods: [ 18 F]-L-FPTP was prepared by [ 18 F]fluoropropylation of 5-hydroxy-L-tryptophan disodium salt and purification on C18 cartridges. The biodistribution of [ 18 F]-L-FPTP was determined in normal mice and the incorporation of [ 18 F]-L-FPTP into tissue proteins was investigated. In vitro competitive inhibition experiments were performed with Hepa1-6 hepatoma cell lines. [ 18 F]-L-FPTP PET imaging was performed on tumor-bearing and inflammation mice and compared with [ 18 F]-L-FEHTP PET. Results: The overall uncorrected radiochemical yield of [ 18 F]-L-FPTP was 21.1 ± 4.4% with a synthesis time of 60 min, the radiochemical purity was more than 99%. Biodistribution studies demonstrate high uptake of [ 18 F]-L-FPTP in liver, kidney, pancreas, and blood at the early phase, and fast clearance in most tissues over the whole observed time. The uptake studies in Hepa1-6 cells suggest that [ 18 F]-L-FPTP is transported by the amino acid transport system B 0,+ , LAT2 and ASC. [ 18 F]-L-FPTP displays good stability and is not incorporated into proteins in vitro. PET imaging shows that [ 18 F]-L-FPTP can be a better potential PET tracer for differentiating tumor from inflammation than [ 18 F]FDG and 5-(3-[ 18 F]fluoroethyloxy)-L-tryptophan ([ 18 F]-L-FEHTP), with high [ 18 F]-L-FPTP uptake ratio (2.53) of tumor to inflammation at 60 min postinjection. Conclusions: Using [ 18 F]fluoropropyl derivatives as intermediates, the new tracer [ 18 F]-L-FPTP was achieved with good yield and

Study on folate receptor PET imaging agent 18F-flurophenethyl folate

International Nuclear Information System (INIS)

Guo Congying; Zhu Jianhua; Qian Jun; Yang Yang; Shen Haixing; Zhang Zhengwei

2009-01-01

This work is aimed at synthesizing an 18 F-labelled folate derivative that can be used as folate-receptor induced tumor PET imaging agent. Under the optimal reaction and testing specification formulated during the cold-labeling experiments, 18 F labeling of folic acid was achieved in three steps of 18 F pre-labeling,bromination and esterification. The receptor binding property of the newly-synthesized folate radio-derivative was studied through β-lactoglobulin binding test. Tumor-bearing nude mice injected with the new compound were used to study whether the derivative can accumulate within tumor issue. Preliminary studies in vitro and in vivo showed that this new PET agent still possessed receptor binding qualities of folic acid. 18 F-flurophenethyl folate remained good affinity and specificity with β-lactoglobulin. Accumulation of activities in tumor tissues was found in tumor-bearing nude mice. A new folate receptor ligand: 18 F-flurophenethyl folate was synthesized,with high yield and good stability. Since the pre-labeling method was used, the fluorine labeling was not directly imposed upon folic acid.In this way, the structure destruction, which happens in high temperature reaction of folic acid, can be avoided. The synthesized folate derivative remained the binding structural quality of folic acid and could bind with the folate-binding protein: β-lactoglobulin. Through the folate receptors located on tumor tissues, 18 F-flurophenethyl folate accumulated in the tumor tissue, exhibiting its potential as a tumor PET imaging agent. (authors)