WorldWideScience

Sample records for potential pet radioligands

  1. Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zha Zhihao; Zhu Lin [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States); Liu Yajing; Du Fenghua; Gan Hongmei; Qiao Jinping [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Kung, Hank F., E-mail: kunghf@gmail.co [Key Laboratory of Radiopharmaceuticals, Beijing Normal University, Ministry of Education, Beijing 100875 (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA 19014 (United States)

    2011-05-15

    }F]7) and NEFT ([{sup 19}F]8). Conclusions: In this research, two new fluorine-18 labeled 2-nitroimidazole derivatives, [{sup 18}F]7 and [{sup 18}F]8, both of which containing in vivo hydrolyzable group, were successfully prepared. Further biological evaluations are warranted to investigate their potential as PET radioligands for imaging tumor.

  2. Development of [11C]/[3H]THK-5351 – A potential novel carbon-11 tau imaging PET radioligand

    International Nuclear Information System (INIS)

    Stepanov, Vladimir; Svedberg, Marie; Jia, Zhisheng; Krasikova, Raisa; Lemoine, Laetitia; Okamura, Nobujuki; Furumoto, Shozo; Mitsios, Nicholas; Mulder, Jan; Långström, Bengt; Nordberg, Agneta; Halldin, Christer

    2017-01-01

    Introduction: Due to the rise in the number of patients with dementia the imperative for finding new diagnostic and treatment options becomes ever more pressing. While significant progress has been made in PET imaging of Aβ aggregates both in vitro and in vivo, options for imaging tau protein aggregates selectively are still limited. Based on the work previously published by researchers from the Tohoku University, Japan, that resulted in the development of [ 18 F]THK-5351, we have undertaken an effort to develop a carbon-11 version of the identical structure - [ 11 C]THK-5351. In parallel, THK-5351 was also labeled with tritium ([ 3 H]THK-5351) for use in in vitro autoradiography (ARG). Methods: The carbon-11 labeling was performed starting with di-protected enantiomeric pure precursor - tert-butyl 5-(6-((2S)-3-fluoro-2-(tetrahydro-2H-pyran-2-yloxy)propoxy)quinolin-2-yl) pyridin-2-yl carbamate, which was reacted with [ 11 C]MeI, using DMF as the solvent and NaH as base, followed by deprotection with trifluoroacetic acid/water mixture, resulting in enantiomerically pure carbon-11 radioligand, [ 11 C]THK-5351 - (S)-1-fluoro-3-(2-(6-([ 11 C]methylamino)pyridin-3-yl)quinolin-6-yloxy) propan-2-ol. Tritium labeling and purification of [ 3 H]THK-5351 were undertaken using similar approach, resulting in [ 3 H]THK-5351 with RCP >99.8% and specific radioactivity of 1.3 GBq/μmol. Results: [ 11 C]THK-5351 was produced in good yield (1900 ± 355 MBq), specific radioactivity (SRA) (361 ± 119 GBq/μmol at EOS + 20 min) and radiochemical purity (RCP) (>99.8%), with enantiomeric purity of 98.7%. [ 3 H]THK-5351 was evaluated for ARG of tau binding in post-mortem human brain tissue using cortical sections from one AD patient and one control subject. [ 3 H]THK-5351 binding density was higher in the AD patient compared to the control subject, the binding was displaced by unlabeled THK-5351 confirming specific [ 3 H]THK-5351 binding.

  3. Synthesis and biological evaluation in rat and cat of [18F]12ST05 as a potential 5-HT6 PET radioligand

    International Nuclear Information System (INIS)

    Tang, Sandrine; Verdurand, Mathieu; Joseph, Benoit; Lemoine, Laetitia; Daoust, Alexia; Billard, Thierry; Fournet, Guy; Le Bars, Didier; Zimmer, Luc

    2007-01-01

    Introduction: 5-hydroxytryptamine (5-HT) 6 receptors represent one of the more recently discovered serotoninergic receptor family. However, no 5-HT 6 positron emission tomography (PET) radiotracer is currently used in clinical imaging studies. The purpose of this study was to propose the first fluorinated PET radiotracer for this brain receptor. Methods: A new compound presenting in vitro high affinity towards the serotoninergic 5-HT 6 receptor, N-[2-(1-[(4-fluorophenyl)sulfonyl]-1H-indol-4-yloxy)ethyl] -N,N-dimethylamine, was labelled with fluorine 18 via a nitro-/fluoronucleophilic substitution. Biological evaluations included (i) in vitro and ex vivo autoradiographies in rat brain and (ii) a PET scan on anaesthetized cat. Results and Conclusion: Although the radioligand showed excellent brain penetration, it did not reveal any specific binding to the 5-HT 6 receptors indicating that this radiotracer is not suitable for mapping 5-HT 6 receptors using PET

  4. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin

    2012-01-01

    The most recently discovered serotonin (5-HT) receptor subtype, 5-HT(7), is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT(7) receptors could provide a significant advance in the understanding of the neurobio...

  5. Radioligands for PET studies of central benzodiazepine receptors and PK (peripheral benzodiazepine) binding sites -current status

    International Nuclear Information System (INIS)

    Pike, V.W.; Osman, S.; Shah, F.; Turton, D.R.; Waters, S.L.; Crouzel, C.; Nutt, D.J.

    1993-01-01

    The status of the radiochemical development and biological evaluation of radioligands for PET studies of central benzodiazepine (BZ) receptors and the so-called peripheral benzodiazepine binding sites, here discriminated and referred to as PK binding sites, is reviewed against current pharmacological knowledge, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies, [N-methyl- 11 C]flumazenil for central BZ receptors, and [N-methyl- 11 C]PK 11195 for PK binding sites. Quality assurance and plasma metabolite analysis are also reviewed for these radioligands and practical recommendations are given on methodology for their performance. (Author)

  6. Synthesis and biological evaluation in rat and cat of [{sup 18}F]12ST05 as a potential 5-HT{sub 6} PET radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Sandrine [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Verdurand, Mathieu [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Joseph, Benoit [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Lemoine, Laetitia [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Daoust, Alexia [CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Billard, Thierry; Fournet, Guy [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); Le Bars, Didier [Institut de Chimie et Biochimie Moleculaires et Supramoleculaires, UMR CNRS 5246, Universite Lyon 1, Universite de Lyon, Lyon, 69677 (Cermep) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France); Zimmer, Luc [Laboratoire de Neuropharmacologie, FRE CNRS 3006, Universite Lyon 1, Universite de Lyon, Lyon, 69373 (FRE CNRS 3006) (France); CERMEP-Imagerie du Vivant, PET Department, Lyon, 69622 (ICBMS) (France)], E-mail: zimmer@univ-lyon1.fr

    2007-11-15

    Introduction: 5-hydroxytryptamine (5-HT){sub 6} receptors represent one of the more recently discovered serotoninergic receptor family. However, no 5-HT{sub 6} positron emission tomography (PET) radiotracer is currently used in clinical imaging studies. The purpose of this study was to propose the first fluorinated PET radiotracer for this brain receptor. Methods: A new compound presenting in vitro high affinity towards the serotoninergic 5-HT{sub 6} receptor, N-[2-(1-[(4-fluorophenyl)sulfonyl]-1H-indol-4-yloxy)ethyl] -N,N-dimethylamine, was labelled with fluorine 18 via a nitro-/fluoronucleophilic substitution. Biological evaluations included (i) in vitro and ex vivo autoradiographies in rat brain and (ii) a PET scan on anaesthetized cat. Results and Conclusion: Although the radioligand showed excellent brain penetration, it did not reveal any specific binding to the 5-HT{sub 6} receptors indicating that this radiotracer is not suitable for mapping 5-HT{sub 6} receptors using PET.

  7. A simplified radiometabolite analysis procedure for PET radioligands using a solid phase extraction with micellar medium

    International Nuclear Information System (INIS)

    Nakao, Ryuji; Halldin, Christer

    2013-01-01

    A solid phase extraction method has been developed for simple and high-speed direct determination of PET radioligands in plasma. Methods: This methodology makes use of a micellar medium and a solid-phase extraction cartridge for displacement of plasma protein bound radioligand and separation of PET radioligands from their radiometabolites without significant preparation. The plasma samples taken from monkey or human during PET measurements were mixed with a micellar eluent containing an anionic surfactant sodium dodecyl sulphate and loaded onto SPE cartridges. The amount of radioactivity corresponding to parent radioligand (retained on the cartridge) and its radioactive metabolites (eluted with micellar eluent) was measured. Results: Under the optimized conditions, excellent separation of target PET radioligands from their radiometabolites was achieved with a single elution and short run-time of 1 min. This method was successfully applied to study the metabolism for 11 C-labelled radioligands in human or monkey plasma. The amount of parent PET radioligands estimated by micellar solid phase extraction strongly corresponded with that determined by radio-LC. The improved throughput permitted the analysis of a large number of plasma samples (up to 13 samples per one PET study) for accurate estimation of metabolite-corrected input function during quantitative PET imaging studies. Conclusion: Solid phase extraction together with micellar medium is fast, sensitive and easy to use, and therefore it is an attractive alternative method to determine relative composition of PET radioligands in plasma

  8. Evaluation of PET Radioligands for the neuronal nicotinic acetylcholine receptor

    International Nuclear Information System (INIS)

    Schoenbaechler, R.; Westera, G.; Nan-Horng Lin

    2002-01-01

    Full text: A-186253.1, a compound made by Abbott laboratories, was labelled with carbon-11 and evaluated as a PET ligand for the neuronal nicotinic acetylcholine receptor (nAChR). The compound was labelled with C-11 by methylation with 11C-MeI of the desmethyl precursor A-183828.1. The affinity of A-186253.1 for the α4β2 and the α7 subtype of the nAChR was determined in displacement studies. PET-studies were performed in rats and pigs Inhibitory constants (K i ) versus cytsine were 461 ± 99 pM for A-186253.1 and versus α-Bungarotoxin >100 μM. which means a very high selectivity for the α4β2-receptor (>227,000). Highest uptake of [ 11 C]-A-186253.1 was observed in the thalamus where an increase in radiotracer uptake was seen until 45 min p.i.. Thereafter, the radiotracer concentration remained constant until the end of the scan indicating slow washout of [ 11 C]-A-186253.1. Application of cold A-186253.1 (0.5 mg/kg) 40 min p.i. resulted in a decrease in radiotracer concentration in the thalamus and the cortex indicating displacement of [ 11 C]-A-186253.1. Blockade studies with cytisine (0.5 mg/kg), a selective ligand for the α4β2 nicotinic receptor, showed just a slight reduction of the radioligand uptake in the thalamus and in the cortex whereas the blockade with cold A-186253.1 (1 mg/kg) resulted in a 50 % reduction. These results suggest, that 50 % of the [ 11 C]-A-186253.1 in the brain corresponds to specifically bound radioligand, but not to the α4β2 subtype of the nicotinic receptor. (author)

  9. Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor

    DEFF Research Database (Denmark)

    Hansen, Hanne Demant; Lacivita, Enza; Di Pilato, Pantaleo

    2014-01-01

    In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best com...

  10. A radiometabolite study of the serotonin transporter PET radioligand [11C]MADAM

    International Nuclear Information System (INIS)

    Gourand, F.; Emond, P.; Bergström, J.P.; Takano, A.; Gulyás, B.; Guilloteau, D.; Barré, L.; Halldin, C.

    2014-01-01

    Introduction: 11 C]MADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown that [ 11 C]MADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO 2 MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. Methods: Comparative PET imaging studies in non-human primate brain with [ 11 C]MADAM and [ 11 C]SOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of [ 11 C]MADAM in rat brain with a view to understand its possible interference for brain imaging with PET. Results: PET imaging studies in non-human primate brain using [ 11 C]SOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of [ 11 C]SOMADAM in non-human primate plasma was approximately 5% at 4 min and 1% at 15 min after [ 11 C]MADAM injection. HPLC analysis of brain sample after [ 11 C]MADAM injection to rats demonstrated that [ 11 C]SOMADAM was not detected in the brain. Conclusions: 11 C]SOMADAM is not superior over [ 11 C]MADAM as a SERT PET radioligand. Nevertheless, [ 11 C]SOMADAM has been identified as a minor labeled metabolite of [ 11 C]MADAM measured in monkey plasma. [ 11 C]SOMADAM was not detected in rat brain

  11. PET radioligands for imaging of Tau pathology: Current status

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Yearn Seong [Dept. of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Kyung Han [Dept. of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul (Korea, Republic of)

    2015-12-15

    The incidence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, continues to soar with the rapid growth of the elderly population, thus creating an enormous social and economic burden. Although disease-modifying drugs to treat AD are not yet available, several candidate drugs are in clinical trials. Most of these drugs are expected to be effective at the early stages of the disease, and therefore the early and accurate diagnosis of AD will be a critical factor in efforts to improve the prognosis of patients with AD. This review focuses on lead radioligands developed to date and their preclinical data in order to facilitate the development of tau-specific positron emission tomography radioligands that are of great interest to the scientific community.

  12. Cerebellar heterogeneity and its impact on PET data quantification of 5-HT receptor radioligands

    DEFF Research Database (Denmark)

    Ganz, Melanie; Feng, Ling; Hansen, Hanne Demant

    2017-01-01

    standardized uptake values (SUV) and nondisplaceable neocortical binding potential (BPND). Statistical difference was assessed with paired nonparametric two-sided Wilcoxon signed-rank tests and multiple comparison corrected via false discovery rate. We demonstrate significant radioligand specific regional...

  13. Use of PET and the radioligand [carbonyl-11C]WAY-100635 in psychotropic drug development

    International Nuclear Information System (INIS)

    Andree, Bengt; Halldin, Christer; Thorberg, Seth-Olov; Sandell, Johan; Farde, Lars

    2000-01-01

    Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine 1A (5-HT 1A ) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT 1A receptor now benefits from the highly selective radioligand [carbonyl- 11 C]WAY-100635 (WAY) for quantitative determination of 5-HT 1A receptors in the primate and human brain in vivo using PET. In this paper, three studies are reviewed to demonstrate the suitability of WAY as radioligand for quantification of central 5-HT 1A receptors in brain and as an applicable tool for drug development. In the first study a monkey model was used to characterize WAY binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive drugs such as buspirone and pindolol occupies 5-HT 1A receptors in the primate brain. Pindolol is an β-adrenoreceptor antagonist with a high affinity to 5-HT 1A receptors. This drug has been suggested in combination with selective serotonin reuptake inhibitors for the treatment of depression and was given to healthy males in the second study. Pindolol induced a marked inhibition of central 5-HT 1A receptors as calculated by the ratio-analysis method and simplified reference tissue model, 2 h after administration of 10 mg as a single oral dose. This observation suggests that pindolol may have a role for the suggested potentiation of selective serotonin reuptake inhibitor treatment of depression. The third study was on robalzotan (NAD-299), a recently developed 5-HT 1A receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 μg/kg IV occupied 5-HT 1A receptors in a dose-dependent and saturable manner with a maximal calculated occupancy of 70-80%. The

  14. Synthesis of 3-[18F]fluoromethyl-BTCP and evaluation as a potential PET radioligand for the dopamine transporter in baboons

    International Nuclear Information System (INIS)

    Ponchant, M.; Crouzel, C.; Varastet, M.; Hantraye, P.;

    1993-01-01

    In an attempt to visualize in vivo the dopamine transporter and evaluate its potential as an imaging tool for monitoring dopamine fiber degeneration by positron emission tomography, the 18 F-positron-emitting analogue of 3-fluoromethyl-1-[2-benzothienyl)-cyclohexyl]-piperidine, [ 18 F]BTCP, was synthesized and tested in a primate model of hemiparkinsonism. When comparing binding ratios between the intact and the dopamine-denervated striatum, there was a modest loss of binding in denervated striatum, suggesting that degeneration of dopaminergic fibers could be detected using 3-[ 18 F]fluoromethyl-BTCP. However due to a high non-specific binding in vivo, the interest of 3-[ 18 F]fluoromethyl-BTCP to image the dopamine reuptake system in vivo appears limited. (author)

  15. Optimization of a Pretargeted Strategy for the PET Imaging of Colorectal Carcinoma via the Modulation of Radioligand Pharmacokinetics.

    Science.gov (United States)

    Zeglis, Brian M; Brand, Christian; Abdel-Atti, Dalya; Carnazza, Kathryn E; Cook, Brendon E; Carlin, Sean; Reiner, Thomas; Lewis, Jason S

    2015-10-05

    Pretargeted PET imaging has emerged as an effective strategy for merging the exquisite selectivity of antibody-based targeting vectors with the rapid pharmacokinetics of radiolabeled small molecules. We previously reported the development of a strategy for the pretargeted PET imaging of colorectal cancer based on the bioorthogonal inverse electron demand Diels-Alder reaction between a tetrazine-bearing radioligand and a transcyclooctene-modified huA33 immunoconjugate. Although this method effectively delineated tumor tissue, its clinical potential was limited by the somewhat sluggish clearance of the radioligand through the gastrointestinal tract. Herein, we report the development and in vivo validation of a pretargeted strategy for the PET imaging of colorectal carcinoma with dramatically improved pharmacokinetics. Two novel tetrazine constructs, Tz-PEG7-NOTA and Tz-SarAr, were synthesized, characterized, and radiolabeled with (64)Cu in high yield (>90%) and radiochemical purity (>99%). PET imaging and biodistribution experiments in healthy mice revealed that although (64)Cu-Tz-PEG7-NOTA is cleared via both the gastrointestinal and urinary tracts, (64)Cu-Tz-SarAr is rapidly excreted by the renal system alone. On this basis, (64)Cu-Tz-SarAr was selected for further in vivo evaluation. To this end, mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts were administered huA33-TCO, and the immunoconjugate was given 24 h to accumulate at the tumor and clear from the blood, after which (64)Cu-Tz-SarAr was administered via intravenous tail vein injection. PET imaging and biodistribution experiments revealed specific uptake of the radiotracer in the tumor at early time points (5.6 ± 0.7 %ID/g at 1 h p.i.), high tumor-to-background activity ratios, and rapid elimination of unclicked radioligand. Importantly, experiments with longer antibody accumulation intervals (48 and 120 h) yielded slight decreases in tumoral uptake but also concomitant

  16. Evaluation of σ-1 receptor radioligand 18F-FTC-146 in rats and squirrel monkeys using PET

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Nielsen, Carsten Haagen

    2014-01-01

    . Pretreatment with known S1R compounds, haloperidol, or BD1047, before radioligand administration, significantly attenuated (18)F-FTC-146 accumulation in all rat brain regions by approximately 85% (P ...-FTC-146 was observed in rat plasma. Preliminary monkey PET/MRI studies demonstrated specific accumulation of (18)F-FTC-146 in the brain (mainly in cortical structures, cerebellum, and vermis) that could be attenuated by pretreatment with haloperidol. HPLC of monkey plasma suggested radioligand metabolism...

  17. Radiosynthesis and evaluation of new α1-adrenoceptor antagonists as PET radioligands for brain imaging

    International Nuclear Information System (INIS)

    Airaksinen, Anu J.; Finnema, Sjoerd J.; Balle, Thomas; Varnäs, Katarina; Bang-Andersen, Benny; Gulyás, Balázs; Farde, Lars; Halldin, Christer

    2013-01-01

    Introduction: Evaluation of the α 1 -adrenoceptors in relation to brain pathophysiology and drug treatment has been hindered by lack of α 1 -adrenoceptor specific radioligands with sufficient brain exposure. Our aim was to develop an α 1 -adrenoceptor specific PET radioligand for brain imaging. Methods: Two sertindole analogues 1-(4-fluorophenyl)-5-(1-methyl-1H-1,2,4-triazol-3-yl)-3-(1-[ 11 C] methylpiperidin-4-yl)-1H-indole [ 11 C]3 and 1-(4-fluorophenyl)-3-(1-[ 11 C]methylpiperidin-4-yl)-5-(pyrimidin-5-yl) -1H-indole ([ 11 C]Lu AA27122) [ 11 C]4 were synthesized and evaluated as α 1 -adrenoceptor PET radioligands in cynomolgus monkey. Compounds 3 and 4 were selected due to their promising in vitro preclinical profile; high affinity and selectivity for the α 1 -adrenoceptor, favourable blood brain barrier permeability rates in Caco-2 monolayers and promising brain tissue/plasma ratio, assessed by equilibrium dialysis of free fraction in plasma and brain homogenate. Results: Compounds [ 11 C]3 and [ 11 C]4 were synthesized from their desmethyl piperidine precursors with high specific radioactivity (> 370 GBq/μmol) using [ 11 C]methyl iodide. The 1,2,4-triazole analogue [ 11 C]3 exhibited poor brain uptake, but the corresponding pyrimidyl analogue [ 11 C]4 exhibited high brain exposure and binding in α 1 -adrenoceptor rich brain regions. However, the binding could not be inhibited by pretreatment with prazosin (0.1 mg/kg and 0.3 mg/kg). The results were extended by autoradiography of [ 11 C]4 binding in human brain sections and competition with antagonists from different structural families, revealing that only a minor portion of the observed binding of [ 11 C]4 in brain was α 1 -adrenoceptor specific. Conclusion: Though [ 11 C]3 and [ 11 C]4 proved not suitable as PET radioligands, the study provided further understanding of structural features influencing brain exposure of the chemical class of compounds related to the antipsychotic drug sertindole. It

  18. A consistent and efficient graphical analysis method to improve the quantification of reversible tracer binding in radioligand receptor dynamic PET studies

    OpenAIRE

    Zhou, Yun; Ye, Weiguo; Brašić, James R.; Crabb, Andrew H.; Hilton, John; Wong, Dean F.

    2008-01-01

    The widely used Logan plot in radioligand receptor dynamic PET studies produces marked noise-induced negative biases in the estimates of total distribution volume (DVT) and binding potential (BP). To avoid the inconsistencies in the estimates from the Logan plot, a new graphical analysis method was proposed and characterized in this study. The new plot with plasma input and with reference tissue input was first derived to estimate DVT and BP. A condition was provided to ensure that the estima...

  19. Radiosynthesis of [11C]D.P.A.-713, [11C]D.P.A.-715 and [11C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    International Nuclear Information System (INIS)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B.; Kassiou, M.; James, M.; Creelman, A.; Fulton, R.; Kassiou, M.; Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C.; Selleri, S.

    2008-01-01

    11 C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon 11 (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[ 11 C]methyl iodide (in D.M.S.O./D.M.F (100/200 μL) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [ 11 C]methyl triflate (in acetone (300μL) containing aq. 3 M NaOH (4μL) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  20. Radiosynthesis of [{sup 11}C]D.P.A.-713, [{sup 11}C]D.P.A.-715 and [{sup 11}C]clinme, selected carbon-11-labelled novel potential radioligands for imaging the peripheral benzodiazepine receptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Thominiaux, C.; Hinnen, F.; Demphel, S.; Le helleix, S.; Chauveau, F.; Boutin, H.; Herard, A.S.; Hantraye, P.; Tavitian, B. [Service Hospitalier Frederic Joliot, I2BM/DSV, 91 - Orsay (France); Kassiou, M.; James, M.; Creelman, A.; Fulton, R. [Sydney Univ., Brain and Mind Research Institute, NSW (Australia); Kassiou, M. [Sydney Univ., Discipline of Medical Radiations, Sciences and School of Chemistry, NSW (Australia); Katsifis, A.; Greguric, I.; Mattner, F.; Loch, C. [Radiopharmaceuticals Research Institute, ANSTO, NSW (Australia); Selleri, S. [Degli Studi di Firenze Univ., Dipt. di Scienze Farmaceutiche (Italy)

    2008-02-15

    {sup 11}C P.K.11195 is not only the oldest, but also the most widely used PET radiotracer for in vivo imaging of the peripheral benzodiazepine receptors (P.B.R. or translocator protein (18 kDa, T.S.P.O.). With the aim of developing a new PET imaging probe for the in vivo study of the P.B.R., two pyrazol [1,5-a]pyrimidineacetamides (D.P.A.-713 and D.P.A.-715) and one imidazol[1,2-a]pyridine-acetamide (C.L.I.N.M.E.) were radiolabelled with the positron emitters carbon{sup 11} (half life: 20.38 min) [1-5]. Briefly, C.L.I.N.M.E. (2-[6-chloro-2(4-iodophenyl)-imidazol[1,2-a]pyridin-3-yl] -N-ethyl-N-methyl-acetamide) was labelled at its methyl-acetamide moity chain from the corresponding nor-analogue using[{sup 11}C]methyl iodide (in D.M.S.O./D.M.F (100/200 {mu}L) containing powdered K.O.H. (3-5 mg) at 110 degrees C for 3 min. D.P.A.-713 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin -3-yl]acetamide) and D.P.A.-715 (N,N-diethyl-2-[2-(4-methoxy-phenyl)-5,7-bis-tri-fluoro-methyl-pyrazolo [1,5-a]pyrimidin-3-yl]acetamide) were labelled at their aromatic methoxy groups from the corresponding nor-derivatives using [{sup 11}C]methyl triflate (in acetone (300{mu}L) containing aq. 3 M NaOH (4{mu}L) at 110 degrees C for 1 min). All radioligands were purified using semi preparative Zorbax reverse phase H.P.L.C., were adequately formulated for in vivo injection within 30 min and were found to be > 95% chemically and radiochemically pure. (N.C.)

  1. Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis

    International Nuclear Information System (INIS)

    Chow, Tiffany W; Verhoeff, Nicolaas PLG; Takeshita, Shinichiro; Honjo, Kie; Pataky, Christina E; St Jacques, Peggy L; Kusano, Maggie L; Caldwell, Curtis B; Ramirez, Joel; Black, Sandra

    2007-01-01

    As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs). We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method. SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p < .001). Quality of the SABRE BP results was preserved relative to the rank order of subjects by manual methods. Intra- and inter-rater ICC were high (>0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs. SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis

  2. Test-retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943

    International Nuclear Information System (INIS)

    Saricicek, Aybala; Chen, Jason; Ruf, Barbara; Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun; Subramanyam, Kalyani; Maloney, Kathleen; Matuskey, David; Deserno, Lorenz; Neumeister, Alexander; Krystal, John H.; Carson, Richard E.; Bhagwagar, Zubin

    2015-01-01

    [ 11 C]P943 is a novel, highly selective 5-HT 1B PET radioligand. The aim of this study was to determine the test-retest reliability of [ 11 C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP ND was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP ND , 0.5 % and 11.5 % for MA1 BP P , 16.7 % and 28.3 % for MA1 BP F , and between 0.2 % and 5.4 % for MRTM2 BP ND . The power analyses showed a greater number of subjects were required using MA1 BP F compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP ND and the lowest with MA1 BP F in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT 1B receptor binding can be obtained using the novel PET radioligand [ 11 C]P943. Quantification of 5-HT 1B receptor binding with MRTM2 BP ND and with MA1 BP P provided the least variability and optimal power for within-subject and

  3. Development of a PET radioligand for the central 5-HT{sub 1B} receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jan D., E-mail: j.d.andersson@ki.s [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Pierson, M. Edward [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Finnema, Sjoerd J.; Gulyas, Balazs [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden); Heys, Richard; Elmore, Charles S. [AstraZeneca Pharmaceuticals, CNS Discovery, Wilmington, DE 19850 (United States); Farde, Lars [AstraZeneca Pharmaceuticals, Neuroscience Clinical, SE-15185 Soedertaelje (Sweden); Halldin, Christer [Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm (Sweden)

    2011-02-15

    Introduction: The serotonin 1B (5-HT{sub 1B}) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT{sub 1B} receptor in the primate brain in vivo. Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [{sup 11}C]methyl triflate on the piperazine structural moiety. In vivo PET evaluation of each radioligand was performed in cynomolgus monkeys and included analysis of radioactive metabolites measured in plasma using high-performance liquid chromatography. Results: In a total of 12 radiosynthesis of the eight radioligands, the mean decay corrected yield was 11%, and the mean specific radioactivity was 299 GBq/{mu}mol (8075 Ci/mmol) at time of administration. Of the eight tested candidates, [{sup 11}C]6 demonstrated the most promising in vivo characteristics, showing high binding in 5-HT{sub 1B} receptor-rich regions and low binding in the cerebellum. When inspecting data from all eight compounds, lipophilicity appeared as a physicochemical property that could be related to favorable in vivo imaging characteristics. Conclusion: Candidate [{sup 11}C]6, i.e., [{sup 11}C]AZ10419369, exhibited high binding potentials in regions known to contain 5-HT{sub 1B} receptors and was nominated for further preclinical characterization and PET examination in human subjects.

  4. Development of two fluorine-18 labeled PET radioligands targeting PDE10A and in vivo PET evaluation in nonhuman primates.

    Science.gov (United States)

    Stepanov, Vladimir; Takano, Akihiro; Nakao, Ryuji; Amini, Nahid; Miura, Shotaro; Hasui, Tomoaki; Kimura, Haruhide; Taniguchi, Takahiko; Halldin, Christer

    2018-02-01

    Phosphodiesterase 10A (PDE10A) is a member of the PDE enzyme family that degrades cyclic adenosine and guanosine monophosphates (cAMP and cGMP). Based on the successful development of [ 11 C]T-773 as PDE10A positron emission tomography (PET) radioligand, in this study our aim was to develop and evaluate fluorine-18 analogs of [ 11 C]T-773. [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were synthesized from the same precursor used for 11 C-labeling of T-773 in a two-step approach via 18 F-fluoromethylation and 18 F-fluoroethylation, respectively, using corresponding deuterated synthons. A total of 12 PET measurements were performed in seven non-human primates. First, baseline PET measurements were performed using High Resolution Research Tomograph system with both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 ; the uptake in whole brain and separate brain regions, as well as the specific binding and tissue ratio between putamen and cerebellum, was examined. Second, baseline and pretreatment PET measurements using MP-10 as the blocker were performed for [ 18 F]FM-T-773-d 2 including arterial blood sampling with radiometabolite analysis in four NHPs. Both [ 18 F]FM-T-773-d 2 and [ 18 F]FE-T-773-d 4 were successfully radiolabeled with an average molar activity of 293 ± 114 GBq/μmol (n=8) for [ 18 F]FM-T-773-d 2 and 209 ± 26 GBq/μmol (n=4) for [ 18 F]FE-T-773-d 4 , and a radiochemical yield of 10% (EOB, n=12, range 3%-16%). Both radioligands displayed high brain uptake (~5.5% of injected radioactivity for [ 18 F]FM-T-773-d 2 and ~3.5% for [ 18 F]FE-T-773-d 4 at the peak) and a fast washout. Specific binding reached maximum within 30 min for [ 18 F]FM-T-773-d 2 and after approximately 45 min for [ 18 F]FE-T-773-d 4 . [ 18 F]FM-T-773-d 2 data fitted well with kinetic compartment models. BP ND values obtained indirectly through compartment models were correlated well with those obtained by SRTM. BP ND calculated with SRTM was 1.0-1.7 in the putamen. The occupancy with 1

  5. Use of PET and the radioligand [carbonyl-{sup 11}C]WAY-100635 in psychotropic drug development

    Energy Technology Data Exchange (ETDEWEB)

    Andree, Bengt; Halldin, Christer; Thorberg, Seth-Olov; Sandell, Johan; Farde, Lars

    2000-07-01

    Positron-emission tomography (PET) provides potential in neuropsychiatric drug development by expanding knowledge of drug action in the living human brain and reducing time consumption and costs. The 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor is of central interest as a target for the treatment of anxiety, depression, and schizophrenia. Research on the clinical significance of the 5-HT{sub 1A} receptor now benefits from the highly selective radioligand [carbonyl-{sup 11}C]WAY-100635 (WAY) for quantitative determination of 5-HT{sub 1A} receptors in the primate and human brain in vivo using PET. In this paper, three studies are reviewed to demonstrate the suitability of WAY as radioligand for quantification of central 5-HT{sub 1A} receptors in brain and as an applicable tool for drug development. In the first study a monkey model was used to characterize WAY binding. It was confirmed that the reference ligand 8-OH-DPAT and psychoactive drugs such as buspirone and pindolol occupies 5-HT{sub 1A} receptors in the primate brain. Pindolol is an {beta}-adrenoreceptor antagonist with a high affinity to 5-HT{sub 1A} receptors. This drug has been suggested in combination with selective serotonin reuptake inhibitors for the treatment of depression and was given to healthy males in the second study. Pindolol induced a marked inhibition of central 5-HT{sub 1A} receptors as calculated by the ratio-analysis method and simplified reference tissue model, 2 h after administration of 10 mg as a single oral dose. This observation suggests that pindolol may have a role for the suggested potentiation of selective serotonin reuptake inhibitor treatment of depression. The third study was on robalzotan (NAD-299), a recently developed 5-HT{sub 1A} receptor antagonist and putative drug with implications for the treatment of depression. In the cynomolgus monkey brain, robalzotan in the dose range 2-100 {mu}g/kg IV occupied 5-HT{sub 1A} receptors in a dose-dependent and saturable

  6. Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173

    Directory of Open Access Journals (Sweden)

    Nedim C. M. Gulaldi

    2013-01-01

    Full Text Available Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R. The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR. Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR=DVS/DVNS, where DVS and DVNS represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r>0.9. Also significant was the correlation between the retention parameter derived from the tissue activity curve (Yret and the retention parameter derived from the impulse response function (fret. Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were

  7. Radiosynthesis and in vivo evaluation of novel radioligands for PET imaging of cerebral 5-HT7 receptors

    DEFF Research Database (Denmark)

    Hansen, Hanne D; Herth, Matthias M; Ettrup, Anders

    2014-01-01

    in the living brain. Here, we present the radiosynthesis and in vivo evaluation of Cimbi-712 (3-{4-[4-(4-methylphenyl)piperazine-1-yl]butyl}p-1,3-dihydro-2H-indol-2-one) and Cimbi-717 (3-{4-[4-(3-methoxyphenyl)piperazine-1-yl]butyl}-1,3-dihydro-2H-indol-2-one) as selective 5-HT7R PET radioligands in the pig...

  8. Synthesis of carbon-11 labeled celecoxib derivatives as new candidate PET radioligands for imaging of inflammation

    International Nuclear Information System (INIS)

    Gao Mingzhang; Wang Min; Miller, Kathy D.; Hutchins, Gary D.; Zheng Qihuang

    2009-01-01

    Cyclooxygenase (prostaglandin endoperoxide synthase or COX) enzyme represents a particularly attractive target in inflammation processes for the development of both therapeutic agents and imaging agents. This study was designed to develop new radioligands for imaging of inflammation using the biomedical imaging technique positron emission tomography (PET). Carbon-11 labeled celecoxib derivatives, [ 11 C]methyl 2-(4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenylsulfonamidooxy) acetate ([ 11 C]6e), [ 11 C]methyl 2-methyl-2-(4-(5-p-tolyl-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)propanoate ([ 11 C]6f), [ 11 C]methyl 2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)acetate ([ 11 C]6g), and [ 11 C]methyl 2-methyl-2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl) phenylsulfonamidooxy)propanoate ([ 11 C]6h), were prepared by O-[ 11 C]methylation of their corresponding precursors using [ 11 C]CH 3 OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15-20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111-185 GBq/μmol.

  9. Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971.

    Science.gov (United States)

    Zanotti-Fregonara, Paolo; Zhang, Yi; Jenko, Kimberly J; Gladding, Robert L; Zoghbi, Sami S; Fujita, Masahiro; Sbardella, Gianluca; Castellano, Sabrina; Taliani, Sabrina; Martini, Claudia; Innis, Robert B; Da Settimo, Federico; Pike, Victor W

    2014-10-15

    The imaging of translocator 18 kDa protein (TSPO) in living human brain with radioligands by positron emission tomography (PET) has become an important means for the study of neuroinflammatory conditions occurring in several neuropsychiatric disorders. The widely used prototypical PET radioligand [(11)C](R)-PK 11195 ([(11)C](R)-1; [N-methyl-(11)C](R)-N-sec-butyl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide) gives a low PET signal and is difficult to quantify, whereas later generation radioligands have binding sensitivity to a human single nucleotide polymorphism (SNP) rs6971, which imposes limitations on their utility for comparative quantitative PET studies of normal and diseased subjects. Recently, azaisosteres of 1 have been developed with improved drug-like properties, including enhanced TSPO affinity accompanied by moderated lipophilicity. Here we selected three of these new ligands (7-9) for labeling with carbon-11 and for evaluation in monkey as candidate PET radioligands for imaging brain TSPO. Each radioligand was readily prepared by (11)C-methylation of an N-desmethyl precursor and was found to give a high proportion of TSPO-specific binding in monkey brain. One of these radioligands, [(11)C]7, the direct 4-azaisostere of 1, presents many radioligand properties that are superior to those reported for [(11)C]1, including higher affinity, lower lipophilicity, and stable quantifiable PET signal. Importantly, 7 was also found to show very low sensitivity to the human SNP rs6971 in vitro. Therefore, [(11)C]7 now warrants evaluation in human subjects with PET to assess its utility for imaging TSPO in human brain, irrespective of subject genotype.

  10. [{sup 11}C]NNC 22-0215, a metabolically stable dopamine D{sub 1} radioligand for PET

    Energy Technology Data Exchange (ETDEWEB)

    Foged, Christian; Halldin, Christer; Swahn, Carl-Gunnar; Ginovart, Nathalie; Karlsson, Per; Lundkvist, Camilla; Farde, Lars

    1998-07-01

    NNC 22-0215 has been found to be a metabolically stable dopamine D{sub 1} antagonist with high affinity and selectivity for D{sub 1} receptors in vitro. We prepared [{sup 11}C]NNC 22-0215 with a specific radioactivity of about 50 GBq/{mu}mol at time of administration. In PET experiments with [{sup 11}C]NNC 22-0215 there was a rapid uptake of radioactivity in the cynomolgus monkey brain (1.8% of total radioactivity injected). Radioactivity accumulated most markedly in the striatum and the neocortex. The striatum to cerebellum ratio was about 4, with specific binding that remained at a plateau level from 50 min to 100 min after injection. Binding in the striatum and neocortex was markedly displaced by SCH 23390, whereas binding in the cerebellum was not reduced. Metabolite studies showed that about 80% of the radioactivity in the monkey plasma represented unchanged radioligand 30 min after injection. The rate of metabolism in monkey plasma in vivo was also determined for a series of structurally related {sup 11}C-labelled benzazepines, previously used as dopamine D{sub 1} receptor ligands for PET. Results indicate a significantly slower rate of metabolism for [{sup 11}C]NNC 22-0215 than for any of the previously labelled benzazepines. Thus [{sup 11}C]NNC 22-0215 has potential for imaging of selective binding to the dopamine D{sub 1} receptors in the human brain with high count rates at time of equilibrium.

  11. Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot.

    Science.gov (United States)

    Veronese, Mattia; Zanotti-Fregonara, Paolo; Rizzo, Gaia; Bertoldo, Alessandra; Innis, Robert B; Turkheimer, Federico E

    2016-04-15

    PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i

  12. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    International Nuclear Information System (INIS)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars; Guilloteau, Denis; Emond, Patrick

    2003-01-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [ 11 C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/μmol). [ 11 C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled β-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [ 11 C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [ 11 C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [ 11 C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  13. [{sup 11}C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Halldin, Christer; Erixon-Lindroth, Nina; Pauli, Stefan; Chou, Yuan-Hwa; Okubo, Yoshiro; Karlsson, Per; Lundkvist, Camilla; Olsson, Hans; Farde, Lars [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, 17176, Stockholm (Sweden); Guilloteau, Denis; Emond, Patrick [INSERM U316 Universite Francois Rabelais, Tours (France)

    2003-09-01

    The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2E-enyl)-2{beta}-carbomethoxy-3{beta}-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [{sup 11}C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/{mu}mol). [{sup 11}C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled {beta}-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [{sup 11}C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [{sup 11}C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [{sup 11}C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man. (orig.)

  14. A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

    Directory of Open Access Journals (Sweden)

    Rodrigo Teodoro

    2015-10-01

    Full Text Available Changes in the expression of α7 nicotinic acetylcholine receptors (α7 nAChRs in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging agents such as radioactively labelled ligands applicable in positron emission tomography (PET. We report on a series of new ligands for α7 nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT3 receptor, we selected the compound 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl-2-fluorodibenzo-[b,d]thiophene 5,5-dioxide (10a for radiolabeling and further evaluation in vivo. Radiosynthesis of [18F]10a was optimized and transferred to an automated module. Dynamic PET imaging studies with [18F]10a in piglets and a monkey demonstrated high uptake of radioactivity in the brain, followed by washout and target-region specific accumulation under baseline conditions. Kinetic analysis of [18F]10a in pig was performed using a two-tissue compartment model with arterial-derived input function. Our initial evaluation revealed that the dibenzothiophene-based PET radioligand [18F]10a ([18F]DBT-10 has high potential to provide clinically relevant information about the expression and availability of α7 nAChR in the brain.

  15. Test-retest reliability of the novel 5-HT{sub 1B} receptor PET radioligand [{sup 11}C]P943

    Energy Technology Data Exchange (ETDEWEB)

    Saricicek, Aybala [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Izmir Katip Celebi University, Department of Psychiatry, Izmir (Turkey); Chen, Jason; Ruf, Barbara [Yale University, Department of Psychiatry, New Haven, CT (United States); Planeta, Beata; Labaree, David; Gallezot, Jean-Dominique; Huang, Yiyun [Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Subramanyam, Kalyani; Maloney, Kathleen [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Matuskey, David [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Yale University, PET Center, Department of Diagnostic Radiology, New Haven, CT (United States); Deserno, Lorenz [Charite - Universitaetsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin (Germany); Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Berlin (Germany); Neumeister, Alexander [Yale University, Department of Psychiatry, New Haven, CT (United States); Mount Sinai School of Medicine, Department of Psychiatry, New York, NY (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Krystal, John H. [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); VA Connecticut Healthcare System, Clinical Neuroscience Division, VA National Center for PTSD, West Haven, CT (United States); Carson, Richard E. [Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bhagwagar, Zubin [Yale University, Department of Psychiatry, New Haven, CT (United States); Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, New Haven, CT (United States); Bristol-Myers Squibb, Wallingford, CT (United States)

    2014-11-27

    [{sup 11}C]P943 is a novel, highly selective 5-HT{sub 1B} PET radioligand. The aim of this study was to determine the test-retest reliability of [{sup 11}C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BP{sub ND} was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BP{sub ND}, 0.5 % and 11.5 % for MA1 BP{sub P}, 16.7 % and 28.3 % for MA1 BP{sub F}, and between 0.2 % and 5.4 % for MRTM2 BP{sub ND}. The power analyses showed a greater number of subjects were required using MA1 BP{sub F} compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BP{sub ND} and the lowest with MA1 BP{sub F} in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT{sub 1B} receptor binding can be obtained using the novel PET radioligand [{sup 11}C]P943. Quantification of 5-HT{sub 1B} receptor binding with MRTM2 BP{sub ND} and with MA1 BP{sub P

  16. 5-HT radioligands for human brain imaging with PET and SPECT

    DEFF Research Database (Denmark)

    Paterson, Louise M; Kornum, Birgitte R; Nutt, David J

    2013-01-01

    The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used...

  17. Radiation Dosimetry of a Novel Adenosine A(2A) Receptor Radioligand [C-11]Preladenant Based on PET/CT Imaging and Ex Vivo Biodistribution in Rats

    NARCIS (Netherlands)

    Zhou, Xiaoyun; Elsinga, Philip H.; Khanapur, Shivashankar; Dierckx, Rudi A. J. O.; de Vries, Erik F. J.; de Jong, Johan R.

    [C-11]Preladenant was developed as a novel adenosine A(2A) receptor PET radioligand. The aim of this study was to determine the radiation dosimetry of [C-11]preladenant and to investigate whether dosimetry estimation based on organ harvesting can be replaced by positron emission tomography

  18. Synthesis, radiolabelling, and evaluation of [11C]PB212 as a radioligand for imaging sigma-1 receptors using PET.

    Science.gov (United States)

    Spinelli, Francesco; Haider, Ahmed; Toscano, Annamaria; Pati, Maria Laura; Keller, Claudia; Berardi, Francesco; Colabufo, Nicola Antonio; Abate, Carmen; Ametamey, Simon M

    2018-01-01

    The Sigma-1 receptor (Sig-1R) has been described as a pluripotent modulator of distinct physiological functions and its involvement in various central and peripheral pathological disorders has been demonstrated. However, further investigations are required to understand the complex role of the Sig-1R as a molecular chaperon. A specific PET radioligand would provide a powerful tool in Sig-1R related studies. As part of our efforts to develop a Sig-1R PET radioligand that shows antagonistic properties, we investigated the suitability of 1-(4-(6-methoxynaphthalen-1-yl)butyl)-4-methylpiperidine (designated PB212) for imaging Sig-1R. PB212 is a Sig-1R antagonist and exhibits subnanomolar affinity ( K i = 0.030 nM) towards Sig-1R as well as good to excellent selectivity over Sig-2R. The radiolabelling of [ 11 C]PB212 was accomplished by O-methylation of the phenolic precursor using [ 11 C]MeI. In vitro autoradiography with [ 11 C]PB212 on WT and Sig-1R KO mouse brain tissues revealed high non-specific binding, however using rat spleen tissues from CD1 mice and Wistar rats, high specific binding was observed. The spleen is known to have a high expression of Sig-1R. In vivo PET experiments in Wistar rats also showed high accumulation of [ 11 C]PB212 in the spleen. Injection of Sig-1R binding compounds, haloperidol (1 mg/kg) or fluspidine (1 mg/kg) shortly before [ 11 C]PB212 administration induced a drastic reduction of radiotracer accumulation, confirming the specificity of [ 11 C]PB212 towards Sig-1R in the spleen. The results obtained herein indicate that although [ 11 C]PB212 is not suitable for imaging Sig-1R in the brain, it is a promising candidate for the detection and quantification of Sig-1Rs in the periphery.

  19. 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.

  20. A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

    DEFF Research Database (Denmark)

    James, Michelle L; Shen, Bin; Zavaleta, Cristina L

    2012-01-01

    of the radioligand in S1R rich regions of the brain. Pre-treatment with 1 mg/kg haloperidol (2), non-radioactive 13, or BD1047 (18) reduced the binding of [(18)F]13 in the brain at 60 min by 80%, 82% and 81% respectively, suggesting that [(18)F]13 accumulation in mouse brain represents specific binding to S1Rs...

  1. Synthesis and biological evaluation of [11C]MK-912 as an α2-adrenergic receptor radioligand for PET studies

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Pleus, Richard C.; Shiue, Grace G.; Rysavy, Joseph A.; Sunderland, John J.; Cornish, Kurtis G.; Young, Steven D.; Bylund, David B.

    1998-01-01

    ABSTRACT. In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro-2H-benzo[b]furo [2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent α 2 -adrenergic receptor antagonist with high affinity (K i = 0.42, 0.26 and 0.03 nM to α 2A , α 2B and α 2C , respectively) and high selectivity (α 2A /α 1A = 240; α 2A /D-1 = 3600; α 2A /D-2 3500; α 2A /5-HT 1 = 700; α 2A /5-HT 2 = 4100). The compound was labeled with 11 C and evaluated in rodents and monkey as a specific radioligand for studying α 2 -adrenergic receptors using PET. [ 11 C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [ 11 C]CH 3 I in (Bu 3 O)P=O at 85 deg. C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/μmol and the radiochemical purity was 97%. The initial uptake of [ 11 C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [ 11 C]MK-912 in rat olfactory tubercle, a brain region with high density of α 2 -adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [ 11 C]MK-912 with a potent α 2 -adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to α 2 -adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [ 11 C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density α 2 -adrenergic receptor brain regions exceeds a few millimeters in diameter

  2. Characterization of [(11)C]Cimbi-36 as an agonist PET radioligand for the 5-HT(2A) and 5-HT(2C) receptors in the nonhuman primate brain

    DEFF Research Database (Denmark)

    Finnema, Sjoerd J; Stepanov, Vladimir; Ettrup, Anders

    2014-01-01

    a more meaningful assessment of available receptors than antagonist radioligands. In the current study we characterized [(11)C]Cimbi-36 receptor binding in the primate brain. On five experimental days, a total of 14 PET measurements were conducted in three female rhesus monkeys. On each day, PET...... agonist radioligand suitable for examination of 5-HT2A receptors in the cortical regions and of 5-HT2C receptors in the choroid plexus of the primate brain....

  3. Pet's research at the SHFJ, Cea, one example: development and validation of a radioligand for the study of the cerebral dopaminergic system

    International Nuclear Information System (INIS)

    Ribeiro, M.J.

    2005-01-01

    The aim of this work is the evaluation of biodistribution and radiation dosimetry of a cocaine analog, the N-(3-iodo-prop-2E-enyl)-2beta-carbo-methoxy-3beta-(4-methyl-phenyl) nor-tropane (PE2I), labeled with carbon 11 ([ 11 C]PE2I). The [ 11 C]PE2I is a selective radioligand for imaging neuronal dopamine transporter (DAT) with positron emission tomography (PET). The DAT is a membrane-bound pre synaptically located protein that regulates the concentration of dopamine at nerve terminals. DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuro-protective therapeutics and, typically, these studies required several successive PET scans. (author)

  4. Candidate PET radioligands for cannabinoid CB{sub 1} receptors: [{sup 18}F]AM5144 and related pyrazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Zizhong, Li [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Gifford, Andrew [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Qian, Liu [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Thotapally, Rajesh [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Yushin, Ding [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States); Makriyannis, Alexandros [Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States); Gatley, S John [Center for Translational Neuroimaging, Brookhaven National Laboratory, Upton, NY 11973 (United States) and Center for Drug Discovery, Northeastern University, Boston, MA 02115 (United States)

    2005-05-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB{sub 1} receptors that respond to {delta}{sup 9}-tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB{sub 1} receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[{sup 18}F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[{sup 18}F]fluoroaniline. The labeled precursor was synthesized from 1-[{sup 18}F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/{mu}mol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB{sub 1} receptors, absolute uptake at <0.003% injected radioactivity per cubic centimeter was lower than the previously reported uptake of the radioiodinated pyrazole AM281. Conclusions: The relatively poor brain uptake of AM5144 and other pyrazole CB{sub 1} receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB{sub 1} receptor that may require very lipophilic ligands.

  5. Candidate PET radioligands for cannabinoid CB1 receptors: [18F]AM5144 and related pyrazole compounds

    International Nuclear Information System (INIS)

    Li Zizhong; Gifford, Andrew; Liu Qian; Thotapally, Rajesh; Ding Yushin; Makriyannis, Alexandros; Gatley, S. John

    2005-01-01

    Introduction: The mammalian brain contains abundant G protein-coupled cannabinoid CB 1 receptors that respond to Δ 9 -tetrahydrocannabinol, the active ingredient of cannabis. The availability of a positron emission tomography (PET) radioligand would facilitate studies of the addictive and medicinal properties of compounds that bind to this receptor. Among the known classes of ligands for CB 1 receptors, the pyrazoles are attractive targets for radiopharmaceutical development because they are antagonists and are generally less lipophilic than the other classes. Methods: A convenient high-yield synthesis of N-(4-[ 18 F]fluorophenyl)-5-(4-bromophenyl)-1-(2,4-dichlorophenyl)- 1H-pyrazole-3-carboxamide (AM5144) was devised by coupling the appropriate pyrazole-3-carboxyl chloride compound with 4-[ 18 F]fluoroaniline. The labeled precursor was synthesized from 1-[ 18 F]fluoro-4-nitrobenzene in 60% radiochemical yield for 10 min using an improved procedure involving sodium borohydride reduction with cobalt chloride catalysis. The product was purified by HPLC to give a specific activity >400 mCi/μmol and a radiochemical purity >95%, and a PET study was conducted in a baboon. Results: Although the regional uptake of AM5144 in baboon brain was consistent with binding to cannabinoid CB 1 receptors, absolute uptake at 1 receptor ligands is not surprising because of their high lipophilicity as compared with most brain PET radiotracers. However, for nine pyrazole compounds for which rodent data are available, brain uptake and calculated logP values are not correlated. Thus, high logP values should not preclude evaluation of radiotracers for targets such as the CB 1 receptor that may require very lipophilic ligands

  6. Age-related decline in dopamine transporter in human brain using PET with a new radioligand [18F]FE-PE2I

    International Nuclear Information System (INIS)

    Shingai, Yoshitoshi; Tateno, Amane; Arakawa, Ryosuke; Sakayori, Takeshi; Kim, WooChan; Okubo, Yoshiro; Suzuki, Hidenori

    2014-01-01

    Dopamine transporter (DAT) density is considered as a marker of pre-synaptic function. Numerous neuroimaging studies have consistently demonstrated an age-related decrease in DAT density in normal human brain. However, the precise degree of the regional decline is not yet clear. The purpose of this study was to evaluate the effect of the normal aging process on DAT densities in human-specific brain regions including the substantia nigra and thalamus using positron emission tomography (PET) with [ 18 F]FE-PE2I, a new PET radioligand with high affinity and selectivity for DAT. Thirty-six healthy volunteers ranging in age from 22 to 80 years were scanned with PET employing [ 18 F]FE-PE2I for measuring DAT densities. Region of interest (ROI)-based analysis was used, and ROIs were manually defined for the caudate, putamen, substantia nigra, thalamus, and cerebellar cortex. DAT binding was quantified using a simplified reference tissue model, and the cerebellum was used as reference region. Estimations of binding potential in the caudate, putamen, substantia nigra, and thalamus were individually regressed according to age using simple regression analysis. Estimates of DAT loss per decade were obtained using the values from the regression slopes. There were 7.6, 7.7, and 3.4% per-decade declines in DAT in the caudate, putamen, and substantia nigra, respectively. By contrast, there was no age-related decline of DAT in the thalamus. [ 18 F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time. (author)

  7. 5-tert-Butyl-2-(4'-[{sup 18}F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA{sub A} receptor radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Li Xuehe; Jung, Yong-Woon; Snyder, Scott E.; Blair, Joseph; Sherman, Philip S.; Desmond, Timothy; Frey, Kirk A. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Kilbourn, Michael R. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States)], E-mail: mkilbour@umich.edu

    2008-07-15

    As potential new ligands targeting the binding site of {gamma}-aminobutyric acid (GABA) receptor ionophore, trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1, 3-dithiane (1) and cis/trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1,3, 3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities (K{sub i}=6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [{sup 18}F]fluorination. In vivo biodistribution studies with trans-[{sup 18}F]1 and trans-[{sup 18}F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons-medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA{sub A} receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.

  8. Characterization of ["1"1C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

    International Nuclear Information System (INIS)

    Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer; Nielsen, Jacob; Bundgaard, Christoffer; Bang-Andersen, Benny; Grimwood, Sarah; Farde, Lars; Finnema, Sjoerd J.

    2017-01-01

    ["1"1C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. ["1"1C]Lu AE92686 has high affinity for PDE10A (IC_5_0 = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional ["1"1C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). ["1"1C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V_T) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V_T values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V_T values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V_T values in target regions remained stable. Both pretreatment drugs significantly decreased ["1"1C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP_N_D) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of ["1"1C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that ["1"1C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia nigra. (orig.)

  9. Characterization of [{sup 11}C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kai-Chun; Stepanov, Vladimir; Amini, Nahid; Martinsson, Stefan; Takano, Akihiro; Halldin, Christer [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Nielsen, Jacob [H. Lundbeck A/S, Synaptic Transmission, Valby (Denmark); Bundgaard, Christoffer; Bang-Andersen, Benny [H. Lundbeck A/S, Discovery Chemistry and DMPK, Valby (Denmark); Grimwood, Sarah [Pfizer Inc., Neuroscience and Pain Research Unit, Cambridge, MA (United States); Farde, Lars [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); AstraZeneca PET Science Center at Karolinska Institutet, Personalized Health Care and Biomarkers, Stockholm (Sweden); Finnema, Sjoerd J. [Karolinska Institutet, Karolinska University Hospital, Department of Clinical Neuroscience, Center for Psychiatric Research, Stockholm (Sweden); Yale University, Department of Radiology and Biomedical Imaging, New Haven, CT (United States)

    2017-02-15

    [{sup 11}C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [{sup 11}C]Lu AE92686 has high affinity for PDE10A (IC{sub 50} = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A. Here, we report characterization of regional [{sup 11}C]Lu AE92686 binding to PDE10A in the nonhuman primate (NHP) brain. A total of 11 PET measurements, seven baseline and four following pretreatment with unlabeled Lu AE92686 or the structurally unrelated PDE10A inhibitor MP-10, were performed in five NHPs using a high resolution research tomograph (HRRT). [{sup 11}C]Lu AE92686 binding was quantified using a radiometabolite-corrected arterial input function and compartmental and graphical modeling approaches. Regional time-activity curves were best described with the two-tissue compartment model (2TCM). However, the distribution volume (V{sub T}) values for all regions were obtained by the Logan plot analysis, as reliable cerebellar V{sub T} values could not be derived by the 2TCM. For cerebellum, a proposed reference region, V{sub T} values increased by ∝30 % with increasing PET measurement duration from 63 to 123 min, while V{sub T} values in target regions remained stable. Both pretreatment drugs significantly decreased [{sup 11}C]Lu AE92686 binding in target regions, while no significant effect on cerebellum was observed. Binding potential (BP{sub ND}) values, derived with the simplified reference tissue model (SRTM), were 13-17 in putamen and 3-5 in substantia nigra and correlated well to values from the Logan plot analysis. The method proposed for quantification of [{sup 11}C]Lu AE92686 binding in applied studies in NHP is based on 63 min PET data and SRTM with cerebellum as a reference region. The study supports that [{sup 11}C]Lu AE92686 can be used for PET examinations of PDE10A binding also in substantia

  10. Synthesis of carbon-11 labelled cyclopentyltheophylline: A radioligand for PET studies of adenosine receptors

    International Nuclear Information System (INIS)

    Yorke, J.C.; Prenant, C.; Crouzel, C.

    1990-01-01

    Adenosine is presently considered as a neuromodulator, and an adenosine system has been described including secretory neurons, with a diffused distribution, specific receptors and a re-uptake system distributed heterogeneously in different anatomic areas. In order to localize the adenosine receptors in vivo by PET, the authors have synthesized the carbon-11 labelled 8-cyclopentyltheophylline, a known adenosine antagonist of A 1 receptors

  11. Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [18F]4-fluorobenzyltrozamicol

    International Nuclear Information System (INIS)

    Clark, P.B.; Gage, H.D.; Brown-Proctor, C.; Buchheimer, N.; Morton, K.A.; Calles-Escandon, J.; Mach, R.H.

    2004-01-01

    The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research. (orig.)

  12. Conception, synthesis and evaluation of fluorescent probes and PET radioligands for the oxytocin and vasopressin receptors

    International Nuclear Information System (INIS)

    Karpenko, Iuliia

    2014-01-01

    In order to better understand the role of OTR and AVPR in ASD, to reveal new features in its pharmacology and signaling and to establish high-throughput screening method on wild-type G protein-coupled receptors, we developed imaging probes for the oxytocin-vasopressin receptors family, namely radiotracers for positron emission tomography and optical probes for fluorescence detection and imaging. The fluorescent ligands have been used to establish TR-FRET binding assay for OTR and to initiate the development the screening assay for the wild-type oxytocin receptor. The PET radiotracers will be shortly tested in mice and monkeys to evaluate their potency in detecting the central oxytocin receptors. (author)

  13. Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, William B. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)]. E-mail: bmathews@petscan.nm.jhu.edu; Zober, Tamas G. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Ravert, Hayden T. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Scheffel, Ursula [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Hilton, John [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Sleep, Darryl [Abbott Laboratories, Abbott Park, IL 60064 (United States); Dannals, Robert F. [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States); Szabo, Zsolt [Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287 (United States)

    2006-01-15

    The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by {sup 11}C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [{sup 11}C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min.

  14. Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

    International Nuclear Information System (INIS)

    Mathews, William B.; Zober, Tamas G.; Ravert, Hayden T.; Scheffel, Ursula; Hilton, John; Sleep, Darryl; Dannals, Robert F.; Szabo, Zsolt

    2006-01-01

    The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by 11 C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [ 11 C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min

  15. Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO) radioligand [{sup 18}F]FEDAA1106: a human whole-body PET study

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Karlsson, Per; Sjoholm, Nils; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Larsson, Stig; Jonsson, Cathrine; Odh, Richard [Karolinska Institutet, Department of Nuclear Medicine, Stockholm (Sweden); Sparks, Richard [CDE Dosimetry Services, Inc., Knoxville, TN (United States); Tawil, Nabil Al [Karolinska University Hospital, Karolinska Trial Alliance, Stockholm (Sweden); Hoffmann, Anja; Zimmermann, Torsten; Thiele, Andrea [Bayer Schering Pharma AG, Berlin (Germany)

    2011-11-15

    [{sup 18}F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [{sup 18}F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 {+-} 9.1 MBq of [{sup 18}F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [{sup 18}F]FEDAA1106 is moderately higher than that of [{sup 18}F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies. (orig.)

  16. Radiosynthesis and evaluation of 11C-CIMBI-5 as a 5-HT2A receptor agonist radioligand for PET

    DEFF Research Database (Denmark)

    Ettrup, Anders; Palner, Mikael; Gillings, Nic

    2010-01-01

    PET brain imaging of the serotonin 2A (5-hydroxytryptamine 2A, or 5-HT(2A)) receptor has been widely used in clinical studies, and currently, several well-validated radiolabeled antagonist tracers are used for in vivo imaging of the cerebral 5-HT(2A) receptor. Access to 5-HT(2A) receptor agonist...... PET tracers would, however, enable imaging of the active, high-affinity state of receptors, which may provide a more meaningful assessment of membrane-bound receptors. In this study, we radiolabel the high-affinity 5-HT(2A) receptor agonist 2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-[(11)C-OCH(3......)]methoxybenzyl)ethanamine ((11)C-CIMBI-5) and investigate its potential as a PET tracer....

  17. Evaluation in vitro and in animals of a new 11C-labeled PET radioligand for metabotropic glutamate receptors 1 in brain

    International Nuclear Information System (INIS)

    Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W.; Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes; Innis, Robert B.

    2013-01-01

    Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC 50 8.9 nM) and partial mGluR5 antagonist (IC 50 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC 50 35.3 nM and 10.2 nM, respectively) were successfully labeled with 11 C and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. 11 C-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC 50 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. 11 C-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. (orig.)

  18. Evaluation in vitro and in animals of a new {sup 11}C-labeled PET radioligand for metabotropic glutamate receptors 1 in brain

    Energy Technology Data Exchange (ETDEWEB)

    Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes [Eli Lilly and Co., Indianapolis, IN (United States); Innis, Robert B. [National Institute of Mental Health, National Institutes of Health, Molecular Imaging Branch, Bethesda, MD (United States); National Institute of Mental Health, Molecular Imaging Branch, Bethesda, MD (United States)

    2013-02-15

    Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC{sub 50} 8.9 nM) and partial mGluR5 antagonist (IC{sub 50} 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC{sub 50} 35.3 nM and 10.2 nM, respectively) were successfully labeled with {sup 11}C and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. {sup 11}C-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC{sub 50} 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. {sup 11}C-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. (orig.)

  19. Characterization of the radioactive metabolites of the 5-HT1A receptor radioligand, [O-methyl-C-11]WAY-100635, in monkey and human plasma by HPLC : Comparison of the behaviour of an identified radioactive metabolite with parent radioligand in monkey using PET

    NARCIS (Netherlands)

    Osman, S; Lundkvist, C; Pike, VW; Halldin, C; McCarron, JA; Swahn, CG; Ginovart, N; Luthra, SK; Bench, CJ; Grasby, PM; Wikstrom, H; Barf, T; Cliffe, IA; Fletcher, A; Farde, L

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (WAY-100635), labelled in the O-methyl group with carbon-11 (t(1/2) = 20.4 min), is a promising radioligand for application with positron emission tomography (PET) to the study of 5-HT1A receptors in living human

  20. Radiosynthesis of (S)-["1"8F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors

    International Nuclear Information System (INIS)

    Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter

    2017-01-01

    Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a ["1"8F]-labelled analog of the highly affine and selective α3β4 ligand (S)-3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)quinuclidine ((S)-T1). (S)-["1"8F]T1 was synthesized from ethynyl-4-["1"8F]fluorobenzene (["1"8F]5) and (S)-azidoquinuclidine by click reaction. After a synthesis time of 130 min (S)-["1"8F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of (S)-["1"8F]T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of (S)-["1"8F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drug AT-1001. These findings make (S)-["1"8F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET. - Highlights: • (S)-["1"8F]T1 is a promising α3ß4 nAChR ligand for PET imaging. • The novel radioligand (S)-["1"8F]T1 was synthesized by click reaction. • The potential of (S)-["1"8F]T1 was shown by in vitro autoradiography and in vivo evaluation in mice.

  1. Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

    2014-10-21

    Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

  2. An improved automated synthesis and in vivo evaluation of PET radioligand for serotonin re-uptake sites. [11C]McN5652X

    International Nuclear Information System (INIS)

    Sasaki, Masahiro; Suhara, Tetsuya; Suzuki, Kazutoshi; Kubodera, Akiko.

    1996-01-01

    Carbon-11 labeled serotonin (5-HT) re-uptake inhibitor, [ 11 C]McN5 652X ((6S,10bR)-trans-( + )-1,2,3,5,6,10b-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline), has recently been reported to be favorable for studying human 5-HT re-uptake site by positron emission tomography (PET) because of its rapid and high specific binding characteristics as radioligands. [ 11 C]McN5652X has been synthesized by S-methylation of the corresponding des-methyl precursor A with [ 11 C]iodomethane. One serious disadvantage of this procedure, however, is the lack of stability of A. The improved method for the synthesis of A has been desired. We have found that the decomposition of A is significantly reduced by adding a protecting agent for SH groups, dithiothreitol (DTT), into the reaction medium immediately after the demethylation of McN5652X. By using this stabilized precursor A, we have developed an automated procedure giving [ 11 C]McN5652X with 98.6±0.4% radiochemical purity in high specific activity (181.3±7.4GBq/μmol). Preclinical evaluation of the produ ct was carried out by injecting the solution of [ 11 C]McN5652X obtained by this procedure into mice. [ 11 C]McN5652X showed the high accumulation into mouse thalamus, striatum and cerebral cortex, organs known to have high level of 5-HT receptor density, after intravenous injection. Human PET studies also showed the high uptakes of this radioligand into the thalamus, striatum and midbrain

  3. Brain radioligands. State of the art and new trends

    International Nuclear Information System (INIS)

    Halldin, C.; Gulyas, B.; Langer, O.; Farde, L.

    2001-01-01

    Non-invasive radioligand imaging methods for brain receptor studies use either short-lived positron-emitting radionuclides such as 11 C and 18 F for positron emission tomography (PET) or single photon-emitting radionuclides such as 123 I for single photon emission computed tomography (SPECT). PET and SPECT use radioligands which are injected intravenously into experimental animals, human volunteers or patients. The main applications of radioligands in brain research concern human neuro psychopharmacology and the discovery and development of novel drugs to be used in the therapy of neurological and psychiatric disorders. A basic problem in PET and SPECT brain receptor studies is the lack of useful radioligands with appropriate binding characteristics. Prerequisite criteria need to be satisfied for a radioligand to reveal target binding sites in vivo. This section will discuss these important criteria and also review recent examples in neuro receptor radioligand development such as selective radioligands for brain monoamine transporters

  4. Synthesis and in-vivo evaluation of C-11 p-PVP-MEMA as a PET radioligand for imaging nicotinic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Paine, T.; Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia); Dolle, F.; Langle, S.; Roger, G.; Lagnel-de Bruin, B.; Hinnen, F.; Valette, H.; Bottlaender, M. [CEA, Serv Hosp Frederic Joliot, Inst Imagerie Biomed, F-91401 Orsay (France); Fulton, R.R.; Henderson, D.J. [Royal Prince Alfred Hosp, Dept PET and Nucl Med, Camperdown, NSW 2050 (Australia); Coster, M.J. [Griffith Univ, Eskitis Inst Cell and Mol Therapies, Nathan, Qld 4121 (Australia); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW2006 (Australia); Brain and Mind Res Inst, Camperdown, NSW2050 (Australia)

    2008-07-01

    Within the class of (4-pyridinyl)vinyl-pyridines developed by Abbott laboratories as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({l_brace}oro-5-((E)-2-pyridin-4-yl-vinyl) pyridin-3-yloxy]-1-methylethyl{r_brace} is the lead compound of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high sub-nanomolar affinity (K-i 0.077 nm-displacement of [H-3](-)cytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-derivative ({l_brace}oro-5-((E)-2-pyridin-4- yl-vinyl) pyridin-3-yloxy]-1-methylethyl{r_brace} as precursor for labelling with the short-lived positron-emitter carbon-11 (T{sub 1/2} = 20.4 min) were synthesized in 10 chemical steps from 2-hydroxy-5-nitropyridine and Boc-D-alanine. N-Alkylation of nor-p-PVP-MEMA with [C-11] methyl iodide afforded [C-11]p-PVP-MEMA ({>=} 98% radiochemically pure, specific activity of 86.4 GBq {mu} mol{sup -1}) in 2% (non-decay corrected and non-optimized) radiochemical yield, in 34 min (including HPLC purification and formulation). Preliminary positron emission tomography PET) results obtained in a Papio hamadryas baboon showed that [C-11] p-PVP-MEMA is not a suitable PET-radioligand. (authors)

  5. Synthesis and in-vivo evaluation of C-11 p-PVP-MEMA as a PET radioligand for imaging nicotinic receptors

    International Nuclear Information System (INIS)

    Paine, T.; Kassiou, M.; Dolle, F.; Langle, S.; Roger, G.; Lagnel-de Bruin, B.; Hinnen, F.; Valette, H.; Bottlaender, M.; Fulton, R.R.; Henderson, D.J.; Coster, M.J.; Kassiou, M.

    2008-01-01

    Within the class of (4-pyridinyl)vinyl-pyridines developed by Abbott laboratories as potent neuronal nicotinic acetylcholine receptor ligands, p-PVP-MEMA ({oro-5-((E)-2-pyridin-4-yl-vinyl) pyridin-3-yloxy]-1-methylethyl} is the lead compound of a novel series that do not display the traditional nicotinic-like pyrrole-ring but still possessing high sub-nanomolar affinity (K-i 0.077 nm-displacement of [H-3](-)cytisine from whole rat brain synaptic membranes). In the present study, p-PVP-MEMA and its nor-derivative ({oro-5-((E)-2-pyridin-4- yl-vinyl) pyridin-3-yloxy]-1-methylethyl} as precursor for labelling with the short-lived positron-emitter carbon-11 (T 1/2 = 20.4 min) were synthesized in 10 chemical steps from 2-hydroxy-5-nitropyridine and Boc-D-alanine. N-Alkylation of nor-p-PVP-MEMA with [C-11] methyl iodide afforded [C-11]p-PVP-MEMA (≥ 98% radiochemically pure, specific activity of 86.4 GBq μ mol -1 ) in 2% (non-decay corrected and non-optimized) radiochemical yield, in 34 min (including HPLC purification and formulation). Preliminary positron emission tomography PET) results obtained in a Papio hamadryas baboon showed that [C-11] p-PVP-MEMA is not a suitable PET-radioligand. (authors)

  6. Developing simplified Regional Potential Evapotranspiration (PET ...

    African Journals Online (AJOL)

    Regional Potential Evapotranspiration (PET) estimation method was developed to estimate the potential evapotranspiration (reference evapotranspiration) over Abbay Basin as a function of basin maximum and minimum temperature, and modulated by site specific elevation data. The method is intended to estimate PET in ...

  7. PET imaging evaluation of [{sup 18}F]DBT-10, a novel radioligand specific to α{sub 7} nicotinic acetylcholine receptors, in nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Hillmer, Ansel T.; Zheng, Ming-Qiang; Li, Songye; Lin, Shu-fei; Holden, Daniel; Labaree, David; Ropchan, Jim; Carson, Richard E.; Huang, Yiyun [Yale University, PET Center, 801 Howard Ave, PO Box 208048, 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)

    2016-03-15

    Positron emission tomography (PET) radioligands specific to α{sub 7} nicotinic acetylcholine receptors (nAChRs) afford in vivo imaging of this receptor for neuropathologies such as Alzheimer's disease, schizophrenia, and substance abuse. This work aims to characterize the kinetic properties of an α{sub 7}-nAChR-specific radioligand, 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-[{sup 18}F]-fluorodibenzo[b,d]thiophene 5,5-dioxide ([{sup 18}F]DBT-10), in nonhuman primates. [{sup 18}F]DBT-10 was produced via nucleophilic substitution of the nitro-precursor. Four Macaca mulatta subjects were imaged with [{sup 18}F]DBT-10 PET, with measurement of [{sup 18}F]DBT-10 parent concentrations and metabolism in arterial plasma. Baseline PET scans were acquired for all subjects. Following one scan, ex vivo analysis of brain tissue was performed to inspect for radiolabeled metabolites in brain. Three blocking scans with 0.69 and 1.24 mg/kg of the α{sub 7}-nAChR-specific ligand ASEM were also acquired to assess dose-dependent blockade of [{sup 18}F]DBT-10 binding. Kinetic analysis of PET data was performed using the metabolite-corrected input function to calculate the parent fraction corrected total distribution volume (V{sub T}/f{sub P}). [{sup 18}F]DBT-10 was produced within 90 min at high specific activities of 428 ± 436 GBq/μmol at end of synthesis. Metabolism of [{sup 18}F]DBT-10 varied across subjects, stabilizing by 120 min post-injection at parent fractions of 15-55 %. Uptake of [{sup 18}F]DBT-10 in brain occurred rapidly, reaching peak standardized uptake values (SUVs) of 2.9-3.7 within 30 min. The plasma-free fraction was 18.8 ± 3.4 %. No evidence for radiolabeled [{sup 18}F]DBT-10 metabolites was found in ex vivo brain tissue samples. Kinetic analysis of PET data was best described by the two-tissue compartment model. Estimated V{sub T}/f{sub P} values were 193-376 ml/cm{sup 3} across regions, with regional rank order of thalamus > frontal cortex > striatum

  8. Electrophilic trifluoromethyl-thiolation reaction and synthesis of radioligand for medicinal PET imaging of l'α-synuclein

    International Nuclear Information System (INIS)

    Alazet, Sebastien

    2015-01-01

    Part 1: More and more applications for fluorinated molecules are being found in various fields, from materials to life sciences. In recent years, a growing interest has emerged in the association of the trifluoromethyl group with heteroatoms such as CF3O or CF3S. The CF3S moiety is of particular interest, because of its high hydrophobicity parameter (π=1.44). Consequently compounds bearing this group are important targets for various applications, in particular in medicinal chemistry and agrochemistry. However, the majority of previous methods described in the literature use toxic reagents under harsh conditions. Trifluoromethane-sulfenamides (1. and 2. generation) have demonstrated their potential in the electrophilic trifluoromethyl-thiolations. Because of their interesting reactivity, these two generations of shelf-stable reagents are now in the toolbox of organic chemists for the trifluoromethyl-thiolation of molecules, providing a convenient method to pursue less toxic pathways. Part 2: α-synuclein aggregation is a neuro-pathological hallmark of many neuro-degenerative diseases including Parkinson's disease (PD) and dementia with Lewy bodies (DLB), collectively termed synucleinopathies. PET imaging can reflect the amount and distribution of alpha-synuclein aggregates in the brain and would be advantageous to use for specific diagnosis of synucleinopathies in pre-symptomatic stages of disease. We focused our interest onto benzimidazole derivatives as small, planar and π-delocalized compounds to design radiotracers of synuclein aggregates. Compounds based on the association of benzimidazole moiety, rigid linker (alkyne and triazole) and another aromatic part have been designed. The radiolabeling could be performed by nucleophilic substitution with K18F during the last step. With this convergent strategy, we could have access to a large series of molecules to be evaluated. (author)

  9. Radioligand binding analysis of α 2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding.

    Science.gov (United States)

    Phan, Jenny-Ann; Landau, Anne M; Jakobsen, Steen; Wong, Dean F; Gjedde, Albert

    2017-11-22

    We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [ 11 C]yohimbine binding in brain to quantify the density and affinity of α 2 adrenoceptors under condition of changing radioligand binding to plasma proteins. We obtained dynamic PET recordings from brain of Spraque Dawley rats at baseline, followed by pharmacological challenge with unlabeled yohimbine (0.3 mg/kg). The challenge with unlabeled ligand failed to diminish radioligand accumulation in brain tissue, due to the blocking of radioligand binding to plasma proteins that elevated the free fractions of the radioligand in plasma. We devised a method that graphically resolved the masking of unlabeled ligand binding by the increase of radioligand free fractions in plasma. The Extended Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50-60% in the presence of unlabeled ligand. The kinetic unmasking of inhibited binding reflected in the increase of the reference volume of distribution yielded estimates of receptor saturation consistent with the binding of unlabeled ligand.

  10. Preparation of a potential positron emission tomographic radioligand for the dopamine transporter

    International Nuclear Information System (INIS)

    Mueller, L.; Halldin, C.; Foged, C.; Karlsson, P.; Hall, H.; Swahn, C.G.; Suzdak, P.D.; Hohlweg, R.; Nielsen, E.B.; Frade, L.

    1994-01-01

    NNC 12-0722 (1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-methyl piperazine) is a new selective inhibitor of the dopamine transporter. [ 11 C]NNC 12-0722 was prepared by N-methylation of the desmethyl compound with [ 11 C]methyl iodide. The total radiochemical yield of [ 11 C]NNC 12-0722 was 40%-50% with an overall synthesis time of 30-35 min. The radiochemical purity was higher than 99% and the specific radioactivity about 1500 Ci/mmol (55 GBq/μmol). Autoradiographic examination of [ 11 C]NNC 12-0722 binding on whole hemisphere cryosections from human brain post mortem demonstrated specific binding in the caudate nucleus and putamen. In a positron emission tomographic examination of [ 11 C]NNC 12-0722 in a cynomolgus monkey there was a rapid uptake of radioactivity in the brain. In the striatum, a region with a high density of dopamine transporters, the radioactivity was two times higher than in the cerebellum. These results indicate that [ 11 C]NNC 12-0722 may be a useful radioligand for labelling of the dopamine transporter in man. (orig.)

  11. In vitro and in vivo characterisation of nor-{beta}-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, K.A. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)]|[Kuopio University Hospital, Clinical Physiology, FIN-70210 Kuopio (Finland); Halldin, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Hall, H. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Lundkvist, C. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Ginovart, N. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Swahn, C.G. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden); Farde, L. [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm (Sweden)

    1997-06-10

    Radiolabelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ({beta}-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2{beta}-Carbomethoxy-3{beta}-(4-iodophenyl)nortropane (nor-{beta}-CIT) is a des-methyl analogue of {beta}-CIT, which in vitro has tenfold higher affinity (IC{sub 50}=0.36 nM) to the serotonin transporter than {beta}-CIT (IC{sub 50}=4.2 nM). Nor-{beta}-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-{beta}-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [{sup 125}I]nor-{beta}-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 {mu}M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [{sup 11}C]nor-{beta}-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [{sup 11}C]nor-{beta}-CIT were 20%-40% higher than those previously obtained with [{sup 11}C]{beta}-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-{beta}-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain. (orig.). With 4 figs.

  12. In vitro and in vivo characterisation of nor-β-CIT: a potential radioligand for visualisation of the serotonin transporter in the brain

    International Nuclear Information System (INIS)

    Bergstroem, K.A.; Halldin, C.; Hall, H.; Lundkvist, C.; Ginovart, N.; Swahn, C.G.; Farde, L.

    1997-01-01

    Radiolabelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2β-Carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT) is a des-methyl analogue of β-CIT, which in vitro has tenfold higher affinity (IC 50 =0.36 nM) to the serotonin transporter than β-CIT (IC 50 =4.2 nM). Nor-β-CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor-β-CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [ 125 I[nor-β-CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 μM) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [ 11 C[nor-β-CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [ 11 C[nor-β-CIT were 20%-40% higher than those previously obtained with [ 11 C[β-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor-β-CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain. (orig.). With 4 figs

  13. Radioligand binding analysis of α 2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

    DEFF Research Database (Denmark)

    Phan, Jenny-Ann; Landau, Anne M.; Jakobsen, Steen

    2017-01-01

    We describe a novel method of kinetic analysis of radioligand binding to neuroreceptors in brain in vivo, here applied to noradrenaline receptors in rat brain. The method uses positron emission tomography (PET) of [11C]yohimbine binding in brain to quantify the density and affinity of α 2...... Inhibition Plot introduced here yielded an estimate of the volume of distribution of non-displaceable ligand in brain tissue that increased with the increase of the free fraction of the radioligand in plasma. The resulting binding potentials of the radioligand declined by 50-60% in the presence of unlabeled...

  14. Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D{sub 2} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Halldin, Christer E-mail: christer.halldin@neuro.ks.se; Dolle, Frederic; Swahn, Carl-Gunnar; Olsson, Hans; Lundkvist, Per Karlsson; Hall, Haakan; Sandell, Johan; Vaufrey, Camilla; Loc' h, Christian; Franzoise; Crouzel, Christian; Maziere, Bernard; Farde, Lars

    1999-07-01

    Epidepride {l_brace}(S)-(-)-N-([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide= {r_brace} binds with a picomolar affinity (K{sub i}=24 pM) to the dopamine D{sub 2} receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D{sub 2} receptors with single photon emission computed tomography (SPECT). Our aim was to label epidepride with carbon-11 for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted with the optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [{sup 11}C]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/{mu}mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [{sup 11}C]epidepride binding. The fraction of unchanged [{sup 11}C]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [{sup 11}C]epidepride. The availability of [{sup 11}C]epidepride allows the PET-verification of the data obtained from quantitation studies with

  15. [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

  16. [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

  17. [{sup 11}C]S.L.(25.1188), a new radioligand to study the monoamine oxidase type B with PET: preclinical characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Saba, W.; Valette, H.; Peyronneau, M.A.; Bramoulle, Y.; Coulon, C.; Dolle, F.; Bottlaender, M. [Service Hospitalier Frederic Joliot, IIBM/DSV, 91 - Orsay (France); Curet, O.; George, P. [Sanofi-Aventis, 92 - Bagneux (France)

    2008-02-15

    Introduction. - Monoamine oxidase (M.A.O.) is a flavin containing enzyme, that catalyzes the oxidative deamination of various amines and neurotransmitters. Two isoforms exist, M.A.O.-A and M.A.O.-B. Variations in M.A.O. activity may be associated to human disease such as Parkinson and Alzheimer disease. Few radiotracers have been developed for M.A.O. PET studies such as [{sup 11}C]deprenyl, an irreversible M.A.O.-B inhibitor. Recently an oxazolidinone derivative, S.L.- 25.1188 ((S)-5-methoxy-methyl-3-[6-(4,4,4-tri-fluoro butoxy)- benzo[d]isoxazol-3-yl]-oxazolidin-2-one), belonging to a new generation of selective and reversible M.A.O.-B inhibitors was developed and showed in vitro a high selectivity for M.A.O.B. [1]. The aim of this study was to characterize [{sup 11}C]S.L.- 25.1188 as radioligand for in vivo PET examination of M.A.O.-B. Materials and methods. - PET studies of the brain distribution were carried out in male Papio anubis baboons. Selectivity and reversibility of [{sup 11}C]S.L.-25.1188 binding for M.A.O.-B was assessed by pre-treatment or displacement experiments (30 min before and after tracer injection, respectively) using reference ligands for M.A.O.-B (deprenyl: 2 mg/kg i.v. and lazabemide: 0.5 mg/kg i.v.) or by displacement experiments using unlabelled S.L.-25.1188 (1 mg/kg, i.v., 30 min after tracer injection). Distribution volume (D.V.) was calculated using 2-tissue-compartment model. The saturable binding following pre-treatment with deprenyl was considered as the specific binding. Results. - After injection, [1{sup 1C}]S.L.-25.1188 presents a rapid phase of distribution in blood (about 5 min), followed by a elimination with T1/2 of 75 min. The Blood to plasma concentration ratio was constant during the experimentation (0.9 {+-} .04) consistent with a similar kinetic of [{sup 11}C]S.L.- 25.1188 in both blood and plasma. Metabolism analysis showed that [{sup 11}C]S.L.-25.1188 is stable in vivo. In the brain, uptake in different areas was

  18. Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635 - explanation of high signal contrast in PET and an aid to biomathematical modelling

    International Nuclear Information System (INIS)

    Osman, Safiye; Lundkvist, Camilla; Pike, Victor W.; Halldin, Christer; McCarron, Julie A.; Swahn, Carl-Gunnar; Farde, Lars; Ginovart, Nathalie; Luthra, Sajinder K.; Gunn, Roger N.; Bench, Christopher J.; Sargent, Peter A.; Grasby, Paul M.

    1998-01-01

    N-(2-(4-(2-Methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), labelled in its amido carbonyl group with 11 C (t 1/2 = 20.4 min), is a promising radioligand for the study of brain 5-HT 1A receptors with positron emission tomography (PET). Thus, in PET experiments in six cynomolgus monkeys and seven healthy male volunteers, [carbonyl- 11 C]WAY-100635 was taken up avidly by brain. Radioactivity was retained in regions rich in 5-HT 1A receptors, such as occipital cortex, temporal cortex and raphe nuclei, but cleared rapidly from cerebellum, a region almost devoid of 5-HT 1A receptors. [Carbonyl- 11 C]WAY-100635 provides about 3- and 10-fold higher signal contrast (receptor-specific to nonspecific binding) than [O-methyl- 11 C]WAY-100635 in receptor-rich areas of monkey and human brain, respectively. To elucidate the effect of label position on radioligand behaviour and to aid in the future biomathematical interpretation of the kinetics of regional cerebral radioactivity uptake in terms of receptor-binding parameters, HPLC was used to measure [carbonyl- 11 C]WAY-100635 and its radioactive metabolites in plasma at various times after intravenous injection. Radioactivity cleared rapidly from monkey and human plasma. Parent radioligand represented 19% of the radioactivity in monkey plasma at 47 min and 8% of the radioactivity in human plasma at 40 min. [Carbonyl- 11 C]desmethyl-WAY-100635 was below detectable limits in monkey plasma and at most a very minor radioactive metabolite in human plasma. [ 11 C]Cyclohexanecarboxylic acid was identified as a significant radioactive metabolite. In human plasma this maximally represented 21% of the radioactivity at 10 min after radioligand injection. All other major radioactive metabolites in monkey and human plasma were even more polar. No-carrier-added [carbonyl- 11 C]cyclohexanecarboxylic acid was prepared in the laboratory and after intravenous administration into cynomolgus monkey was

  19. PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013.

    Science.gov (United States)

    Kulkarni, Harshad R; Singh, Aviral; Schuchardt, Christiane; Niepsch, Karin; Sayeg, Manal; Leshch, Yevgeniy; Wester, Hans-Juergen; Baum, Richard P

    2016-10-01

    A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with 68 Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with 177 Lu-PSMA ligands. 68 Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring. Our comprehensive experience over the last 3 years using different radioligands indicates that PRLT is highly effective for the treatment of mCRPC, even in advanced cases, and potentially lends a significant benefit to overall and progression-free survival. Additionally, significant improvement in clinical symptoms and excellent palliation of pain can be achieved. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  20. [O-methyl-{sup 11}C]{beta}-CIT-FP, a potential radioligand for quantitation of the dopamine transporter: Preparation, autoradiography, metabolite studies, and positron emission tomography examinations

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla; Halldin, Christer; Swahn, Carl-Gunnar; Hall, Haakan; Karlsson, Per; Nakashima, Yoshifumi; Wang, Shaoyin; Milius, Richard A.; Neumeyer, John L.; Farde, Lars

    1995-10-01

    {beta}-CIT-FP [N-(3-fluoropropyl)-2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane] is a cocaine analogue with a high affinity for the dopamine transporter. [O-methyl-{sup 11}C]{beta}-CIT-FP ([{sup 11}C]{beta}-CIT-FP) was prepared byO -alkylation of the free acid with [{sup 11}C]methyl iodide. The total radiochemical yield of [{sup 11}C]{beta}-CIT-FP was 50 to 60% with an overall synthesis time of 30 min. The radiochemical purity was >99%, and the specific radioactivity at time of injection was about 37 GBq/{mu}mol (1000 Ci/mmol). Autoradiographic examination of [{sup 11}C]{beta}-CIT-FP binding in human brain postmortem demonstrated specific binding in the caudate nucleus and putamen. Positron emission tomography (PET) examination of [{sup 11}C]{beta}-CIT-FP in a Cynomolgus monkey demonstrated accumulation in the striatum with a striatum-to-cerebellum ratio of about 8 after 60 min. Equilibrium in the striatum was attained within 70 to 90 min. The radioactivity ratios of thalamus/cerebellum and neocortex/cerebellum were about 2 and 1.5, respectively. In a displacement experiment, radioactivity in the striatum but not in the cerebellum was reduced after injection of {beta}-CIT, indicating that striatal radioactivity following injection of [{sup 11}C]{beta}-CIT-FP is associated with dopamine transporter sites and that the binding is reversible. The fraction of the total radioactivity in plasma representing [{sup 11}C]{beta}-CIT-FP determined by high-performance liquid chromatography (HPLC) was 84% at 15 min and 50% at 95 min. [{sup 11}C]{beta}-CIT-FP should be a useful PET radioligand for the quantitation of dopamine transporters in the human brain in vivo.

  1. [{sup 18}F]L.B.T.-999, a new radioligand to study the dopamine transporter with PET: characterization in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Saba, W.; Schollhorn, M.A.; Valette, H.; Dolle, F.; Bottlaender, M. [Service Hospitalier Frederic Joliot, DRM/DSV, 91 - Orsay (France); Chalon, S.; Garreau, L.; Emond, P.; Guilloteau, D. [Institut National de la Sante et de la Recherche Medicale (INSERM), U619, 37 - Tours (France); Deloye, J.B. [Cyclopharma, 63 - Clermont Ferrand (France)

    2008-02-15

    The dopamine transporter (D.A.T.) is the main regulator of the synaptic concentration of dopamine in the brain and plays a key role in many neurological and psychiatric diseases. The goal of the study was to characterize the properties of [{sup 18}F]L.B.T.-999 in baboons. Regional brain distribution was examined in vitro by autoradiographic studies on brain sections and in vivo by PET. Results of in vitro autoradiographic studies were in agreement with the localisation of the D.A.T. and revealed high level of [{sup 18}F]L.B.T.-999 binding in the putamen and caudate, moderate level in the midbrain, and low level in the cortex and cerebellum. In PET study, the time course of the concentration of [{sup 18}F]L.B.T.-999 in different regions of the brain showed that the highest accumulation of [{sup 18}F]L.B.T.-999 was observed in the striatum with a peak uptake at 50 min (maximum = 5.7 {+-} 1.7 and 4.7 {+-}1.0% I.D./100 ml in putamen and caudate nucleus respectively, n 5). The radioactivity uptake peaked at 8 min in the midbrain (2.3 {+-} 1.2% I.D./100 ml) and decreased rapidly as a function of time. The lowest uptake was observed in the cortex (0.62 {+-}0.1 % I.D./100 ml, at 50 min) and in the cerebellum (0.44 {+-} 0.08% I.D./100 ml, at 50 min). In the test retest studies (n = 3) the variability of the uptake was 5% in the putamen and 6% in the caudate. Following HPLC analysis of plasma samples, [{sup 18}F]L.B.T.-999 was rapidly metabolized. Unchanged [{sup 18}F]L.B.T.-999 accounted for around 21% and 7% of the radioactivity at 30 and 120 min post-injection respectively. The region to cerebellum radioactivity ratio was calculated. This ratio reached a maximum at 110 min post injection (22.1 {+-} 4.6 and 18.8 {+-} 2.1 in the putamen and the caudate respectively) and remained stable during the time of the PET scan (4 h). This ratio was 4.21 {+-} 0.92, 2.0 {+-} 0.3 and 1.6 {+-} 0.2 in the midbrain, thalamus, and cortical structure at 110 min post-injection. Binding

  2. Radiosynthesis and in vivo evaluation of [{sup 11}C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A

    Energy Technology Data Exchange (ETDEWEB)

    De Bruyne, Sylvie [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium); La Regina, Giuseppe [Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universita di Roma, I-00185 Rome (Italy); Staelens, Steven [IBITECH-Medisip, Ghent University-IBBT, 9000 Ghent (Belgium); Wyffels, Leonie [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium); Deleye, Steven [IBITECH-Medisip, Ghent University-IBBT, 9000 Ghent (Belgium); Silvestri, Romano [Istituto Pasteur, Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universita di Roma, I-00185 Rome (Italy); De Vos, Filip [Laboratory for Radiopharmacy, Ghent University, 9000 Ghent (Belgium)], E-mail: filipx.devos@ugent.be

    2010-05-15

    Introduction: Since MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [{sup 11}C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties. Methods: The radiolabelling of [{sup 11}C]-RS 2315 and [{sup 11}C]-RS 2360 was accomplished by alkylation of their amide precursors with [{sup 11}C]CH{sub 3}I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [{sup 11}C]-RS 2360. Results: Both tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [{sup 11}C]-RS 2360 was more stable than [{sup 11}C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [{sup 11}C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [{sup 11}C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points. Conclusions: [{sup 11}C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [{sup 11}C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.

  3. Radiosynthesis and in vivo evaluation of [11C]-labelled pyrrole-2-carboxamide derivates as novel radioligands for PET imaging of monoamine oxidase A

    International Nuclear Information System (INIS)

    De Bruyne, Sylvie; La Regina, Giuseppe; Staelens, Steven; Wyffels, Leonie; Deleye, Steven; Silvestri, Romano; De Vos, Filip

    2010-01-01

    Introduction: Since MAO-A is an enzyme involved in the metabolism of neurotransmitters, fluctuations in MAO-A functionality are associated with psychiatric and neurological disorders as well as with tobacco addiction and behaviour. This study reports the radiolabelling of two [ 11 C]-labelled pyrrole-2-carboxamide derivates, RS 2315 and RS 2360, along with the characterization of their in vivo properties. Methods: The radiolabelling of [ 11 C]-RS 2315 and [ 11 C]-RS 2360 was accomplished by alkylation of their amide precursors with [ 11 C]CH 3 I. Biodistribution, blocking and metabolite studies of both tracers were performed in NMRI mice. Finally, a PET study in Sprague-Dawley rats was performed for [ 11 C]-RS 2360. Results: Both tracers were obtained in a radiochemical yield of approximately 30% with radiochemical purity of >98%. Biodistribution studies showed high brain uptake followed by rapid brain clearance for both radiotracers. In the brain, [ 11 C]-RS 2360 was more stable than [ 11 C]-RS 2315. Blocking studies in mice could not demonstrate specificity of [ 11 C]-RS 2315 towards MAO-A or MAO-B. The blocking and imaging study with [ 11 C]-RS 2360 on the other hand indicated specific binding in MAO-A at the earliest time points. Conclusions: [ 11 C]-RS 2315 displayed a high nonspecific binding and is therefore not suitable for visualization of MAO-A in vivo. [ 11 C]-RS 2360 on the other hand has potential for mapping MAO-A since specific binding is demonstrated.

  4. The potential of carbon-11 and fluorine-18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

    International Nuclear Information System (INIS)

    Damont, Annelaure; Roeda, Dirk; Dolle, Frederic

    2013-01-01

    The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is up-regulated in the brain of subjects suffering from neuro-degenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to micro-glia activation making thus the TSPO a marker of choice of neuro-inflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980's with the preparation of the 3-iso-quinolinecarboxamide [ 11 C]PK11195. To date, an impressive number of promising compounds - [ 11 C]PK11195-challengers - have been developed; some radioligands - for example, [ 11 C]PBR28, [ 11 C]DPA-713, [ 18 F]FEDAA1106 and [ 18 F]DPA-714 - are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [ 11 C]methylations using [ 11 C]MeI or [ 11 C]MeOTf and SN2- type nucleophilic aliphatic [ 18 F]fluorinations - two processes illustrating the state-of-the-art arsenal of reactions that involves these two short-lived radioisotopes - but alternative processes, such as [ 11 C]carbonylations using [ 11 C]CO and [ 11 C]COCl 2 as well as SNAr-type nucleophilic [ 18 F]fluorinations, have also been reported and as such, reviewed herein. (authors)

  5. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)nAChR bind......Small-molecule α(7) nicotinic acetylcholine receptor (α(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled α(7)nAChR PET tracer would be important for in vivo quantification of α(7)n...

  6. 11C-NS14492 as a novel PET radioligand for imaging cerebral alpha7 nicotinic acetylcholine receptors: in vivo evaluation and drug occupancy measurements

    DEFF Research Database (Denmark)

    Ettrup, Anders; Mikkelsen, Jens D; Lehel, Szabolcs

    2011-01-01

    Small-molecule a(7) nicotinic acetylcholine receptor (a(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled a(7)nAChR PET tracer would be important for in vivo quantification of a(7)nAChR bind......Small-molecule a(7) nicotinic acetylcholine receptor (a(7)nAChR) agonists are currently validated for use as treatment for cognitive disturbances in schizophrenia and in Alzheimer disease. A suitable radiolabeled a(7)nAChR PET tracer would be important for in vivo quantification of a(7)n...

  7. Preclinical evaluation and quantification of [(18)F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    OpenAIRE

    Casteels, Cindy; Koole, Michel; Celen, Sofie; Bormans, Guy; Van Laere, Koen

    2012-01-01

    PURPOSE: [(18)F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [(18)F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. METHODS: Dynamic small-animal PET scans with [(18)F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blo...

  8. Synthesis, radiolabeling and in vivo evaluation of [{sup 11}C]RAL-01, a potential phosphodiesterase 5 radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsen, Steen [PET Centre, Aarhus University Hospitals, 8000 Aarhus (Denmark)]. E-mail: steen@pet.auh.dk; Kodahl, Gitte Munkebo [PET Centre, Aarhus University Hospitals, 8000 Aarhus (Denmark); Olsen, Aage Kristian [PET Centre, Aarhus University Hospitals, 8000 Aarhus (Denmark); Cumming, Paul [PET Centre, Aarhus University Hospitals, 8000 Aarhus (Denmark); Centre for Functionally Integrative Neuroscience, Aarhus University, Aarhus (Denmark)

    2006-07-15

    Very few tracers are available for imaging studies of second messenger systems. We developed a radiosynthesis for the phosphodiesterase (PDE) 5 inhibitor [{sup 11}C]RAL-01. Whole body distribution studies using positron emission tomography (PET) revealed a time-dependant passage through the liver and accumulation of radioactivity in the bile of the Landrace pig. Displaceable binding was readily discerned in the myocardium, and traces of binding were seen in pulmonary tissue, consistent with the use of this class of drug in the treatment of pulmonary hypertension and heart failure. [{sup 11}C]RAL-01 readily entered the brain and obtained an equilibrium distribution volume of 4-5 ml g{sup -1}. Mean parametric images suggested the presence of a small displaceable binding component, but this binding was not significant in the present group of three pigs. Thus, [{sup 11}C]RAL-01 shows considerable promise for PET studies of biliary elimination and of PDE5 binding in the cardiovascular system. However, analogues of higher affinity may be required for investigations of central nervous system binding sites.

  9. [{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

    2010-03-15

    The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 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{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 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 [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

  10. Preclinical evaluation and quantification of [18F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    International Nuclear Information System (INIS)

    Casteels, Cindy; Koole, Michel; Laere, Koen van; Celen, Sofie; Bormans, Guy

    2012-01-01

    [ 18 F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [ 18 F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [ 18 F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V T ) of [ 18 F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [ 18 F]MK-9470 in arterial plasma samples was 80 ± 23 % at 10 min, 38 ± 30 % at 40 min and 13 ± 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V T values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability (≤10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [ 18 F]MK-9470 V T , but was correlated. A correlation between [ 18 F]MK-9470 V T and SUV in the brain was also found (R 2 = 0.26-0.33; p ≤ 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [ 18 F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  11. Preclinical evaluation and quantification of [{sup 18}F]MK-9470 as a radioligand for PET imaging of the type 1 cannabinoid receptor in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Casteels, Cindy [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); University Hospital Gasthuisberg, Division of Nuclear Medicine, Leuven (Belgium); Koole, Michel; Laere, Koen van [K.U. Leuven, University Hospital Leuven, Division of Nuclear Medicine, Leuven (Belgium); K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); Celen, Sofie; Bormans, Guy [K.U. Leuven, MoSAIC, Molecular Small Animal Imaging Center, Leuven (Belgium); K.U. Leuven, Laboratory for Radiopharmacy, Leuven (Belgium)

    2012-09-15

    [{sup 18}F]MK-9470 is an inverse agonist for the type 1 cannabinoid (CB1) receptor allowing its use in PET imaging. We characterized the kinetics of [{sup 18}F]MK-9470 and evaluated its ability to quantify CB1 receptor availability in the rat brain. Dynamic small-animal PET scans with [{sup 18}F]MK-9470 were performed in Wistar rats on a FOCUS-220 system for up to 10 h. Both plasma and perfused brain homogenates were analysed using HPLC to quantify radiometabolites. Displacement and blocking experiments were done using cold MK-9470 and another inverse agonist, SR141716A. The distribution volume (V{sub T}) of [{sup 18}F]MK-9470 was used as a quantitative measure and compared to the use of brain uptake, expressed as SUV, a simplified method of quantification. The percentage of intact [{sup 18}F]MK-9470 in arterial plasma samples was 80 {+-} 23 % at 10 min, 38 {+-} 30 % at 40 min and 13 {+-} 14 % at 210 min. A polar radiometabolite fraction was detected in plasma and brain tissue. The brain radiometabolite concentration was uniform across the whole brain. Displacement and pretreatment studies showed that 56 % of the tracer binding was specific and reversible. V{sub T} values obtained with a one-tissue compartment model plus constrained radiometabolite input had good identifiability ({<=}10 %). Ignoring the radiometabolite contribution using a one-tissue compartment model alone, i.e. without constrained radiometabolite input, overestimated the [{sup 18}F]MK-9470 V{sub T}, but was correlated. A correlation between [{sup 18}F]MK-9470 V{sub T} and SUV in the brain was also found (R {sup 2} = 0.26-0.33; p {<=} 0.03). While the presence of a brain-penetrating radiometabolite fraction complicates the quantification of [{sup 18}F]MK-9470 in the rat brain, its tracer kinetics can be modelled using a one-tissue compartment model with and without constrained radiometabolite input. (orig.)

  12. Synthesis and biological evaluation of I-125/I-123-labelled analogues of citalopram and escitalopram as potential radioligands for imaging of the serotonin transporter

    DEFF Research Database (Denmark)

    Madsen, Jacob; Elfving, Betina; Frokjaer, Vibe G.

    2011-01-01

    Two novel radioligands for the serotonin transporter (SERT), [I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-2) and S-[I-125]{3-[5-iodo-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-1-yl]-propyl}-dimethylamine ([I-125]-(S)-2) were synthesized in a ...... of the radioligand in imaging cortical SERT distribution in vivo. These data suggest that the iodine-labelled derivatives of citalopram and escitalopram are not superior to another SPECT tracer for the SERT, namely [I-123] ADAM....

  13. Synthesis and evaluation of [11C]Cimbi-806 as a potential PET ligand for 5-HT7 receptor imaging

    DEFF Research Database (Denmark)

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

    2012-01-01

    )-N,N-dimethylethanamine ([(11)C]Cimbi-806) as a radioligand for imaging brain 5-HT(7) receptors with positron emission tomography (PET). Precursor and reference compound was synthesized and subsequent (11)C-labelling with [(11)C]methyltriflate produced [(11)C]Cimbi-806 in specific activities ranging from 50 to 300 GBq...... of appropriate in vivo blocking with a 5-HT(7) receptor selective compounds renders the conclusion that [(11)C]Cimbi-806 is not an appropriate PET radioligand for imaging the 5-HT(7) receptor in vivo....

  14. Radioligand Recognition of Insecticide Targets.

    Science.gov (United States)

    Casida, John E

    2018-04-04

    Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH + ubiquinone oxidoreductase. Pyrethroids and other Na + channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

  15. PET radioligand injection for pig neuroimaging

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen; Munk, Ole Lajord; Landau, Anne M.

    2018-01-01

    Pigs are useful models in neuroimaging studies with positron emission tomography. Radiolabeled ligands are injected intravenously at the start of the scan and in pigs, the most easily accessible route of administration is the ear vein. However, in brain studies the short distance between the brai...

  16. Potential Applications of PET/MR Imaging in Cardiology.

    Science.gov (United States)

    Ratib, Osman; Nkoulou, René

    2014-06-01

    Recent advances in hybrid PET/MR imaging have opened new perspectives for cardiovascular applications. Although cardiac MR imaging has gained wider adoption for routine clinical applications, PET images remain the reference in many applications for which objective analysis of metabolic and physiologic parameters is needed. In particular, in cardiovascular diseases-more specifically, coronary artery disease-the use of quantitative and measurable parameters in a reproducible way is essential for the management of therapeutic decisions and patient follow-up. Functional MR images and dynamic assessment of myocardial perfusion from transit of intravascular contrast medium can provide useful criteria for identifying areas of decreased myocardial perfusion or for assessing tissue viability from late contrast enhancement of scar tissue. PET images, however, will provide more quantitative data on true tissue perfusion and metabolism. Quantitative myocardial flow can also lead to accurate assessment of coronary flow reserve. The combination of both modalities will therefore provide complementary data that can be expected to improve the accuracy and reproducibility of diagnostic procedures. But the true potential of hybrid PET/MR imaging may reside in applications beyond the domain of coronary artery disease. The combination of both modalities in assessment of other cardiac diseases such as inflammation and of other systemic diseases can also be envisioned. It is also predicted that the 2 modalities combined could help characterize atherosclerotic plaques and differentiate plaques with a high risk of rupture from stable plaques. In the future, the development of new tracers will also open new perspectives in evaluating myocardial remodeling and in assessing the kinetics of stem cell therapy in myocardial infarction. New tracers will also provide new means for evaluating alterations in cardiac innervation, angiogenesis, and even the assessment of reporter gene technologies

  17. Radioligand assay in reproductive biology

    International Nuclear Information System (INIS)

    Korenman, S.G.; Sherman, B.M.

    1975-01-01

    Radioligand assays have been developed for the principal reproductive steroids and peptide hormones. Specific binding reagents have included antibodies, plasma binders, and intracellular receptors. In each assay, problems of specificity, sensitivity, and nonspecific inhibitors were encountered. Many features of the endocrine physiology in childhood, during puberty, and in adulthood have been characterized. Hormonal evaluations of endocrine disorders of reproduction are characterized on the basis of their characteristic pathophysiologic alterations. (U.S.)

  18. Dual-time FDG-PET/CT in patients with potential breast cancer recurrence

    DEFF Research Database (Denmark)

    Baun, Christina; Falch Braas, Kirsten; Gerke, Oke

    Dual-time FDG-PET/CT in patients with potential breast cancer recurrence: head-to-head comparison with CT and bonescintigraphy......Dual-time FDG-PET/CT in patients with potential breast cancer recurrence: head-to-head comparison with CT and bonescintigraphy...

  19. Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central α2-adrenoceptors

    International Nuclear Information System (INIS)

    Hume, S.P.; Hirani, E.; Opacka-Juffry, J.; Osman, S.; Myers, R.; Gunn, R.N.; McCarron, J.A.; Pike, V.W.; Clark, R.D.; Melichar, J.; Nutt, D.J.

    2000-01-01

    Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central α 2 -adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of α 2 -adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [ 11 C]RS-79948-197 11 C]RS-15385-197 3 H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon-11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of ∝5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90-120 min after radioligand injection, encouraged the development of [O-methyl- 11 C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of α 2 -adrenoceptors in human brain, it was concluded that [O-methyl- 11 C]RS-15385

  20. Difference in brain distributions of carbon 11-labeled 4-hydroxy-2(1H)-quinolones as PET radioligands for the glycine-binding site of the NMDA ion channel

    Energy Technology Data Exchange (ETDEWEB)

    Fuchigami, Takeshi [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Haradahira, Terushi [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan)], E-mail: terushi@niu.ac.jp; Fujimoto, Noriko [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Okauchi, Takashi; Maeda, Jun; Suzuki, Kazutoshi; Suhara, Tetsuya [Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555 (Japan); Yamamoto, Fumihiko; Sasaki, Shigeki; Mukai, Takahiro [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan); Yamaguchi, Hiroshi [Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Ogawa, Mikako [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Magata, Yasuhiro [Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Molecular Imaging Frontier Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192 (Japan); Maeda, Minoru [Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582 (Japan)

    2008-02-15

    High-affinity iodine- and ethyl-C-5 substituted analogs of 4-hydroxy-3-(3-[{sup 11}C]methoxyphenyl)-2(1H)-quinolone ([{sup 11}C]4HQ) were synthesized as new positron emission tomography radioligands for the glycine-binding sites of the N-methyl-D-aspartate (NMDA) ion channel. Although both radioligands showed high in vitro specific binding to rat brain slices, their binding characteristics were quite different from each other. 5-Ethyl-[{sup 11}C]4HQ (5Et-[{sup 11}C]4HQ) showed higher in vitro binding in the forebrain regions than in the cerebellum, bindings that were strongly inhibited by both glycine-site agonists and antagonists. In contrast, 5-iodo-[{sup 11}C]4HQ (5I-[{sup 11}C]4HQ) showed a homogeneous in vitro binding throughout the brain, which was inhibited by antagonists but not by agonists. This difference in in vitro binding between 5Et-[{sup 11}C]4HQ and 5I-[{sup 11}C]4HQ was quite similar to that previously observed between [{sup 11}C]L-703,717 and [{sup 11}C]4HQ, both glycine-site antagonists. In vivo brain uptakes of these {sup 11}C-labeled 4-hydroxyquinolones were examined in mice. Initial brain uptakes of 5Et- and 5I-[{sup 11}C]4HQ at 1 min after intravenous injections were comparable to that of [{sup 11}C]4HQ, but they were 1.3-2.1 times higher than that of [{sup 11}C]L-703,717. The treatment with an anticoagulant, warfarin, only slightly increased the initial uptakes of [{sup 11}C]4HQ and 5Et-[{sup 11}C]4HQ in contrast to [{sup 11}C]L-703,717. The in vivo regional brain distributions were slightly different between the two radioligands. Pretreatment with nonradioactive ligand (2 mg/kg) slightly inhibited the binding of 5Et-[{sup 11}C]4HQ (16-36% inhibition) but not that of 5I-[{sup 11}C]4HQ. In this study, it was found that a small structural change in [{sup 11}C]4HQ resulted in a major change in binding characteristics and distributions, suggesting the existence of two binding sites for [{sup 11}C]4-hydroxyquinolones on the NMDA ion channel

  1. PET

    DEFF Research Database (Denmark)

    Mariager, Rasmus Mølgaard; Schmidt, Regin; Heiberg, Morten Rievers

    PET handler om den hemmelige tjenestes arbejde under den kolde krig 1945-1989. Her fortæller Regin Schmidt, Rasmus Mariager og Morten Heiberg om de mest dramatiske og interessante sager fra PET's arkiv. PET er på flere måder en udemokratisk institution, der er sat til at vogte over demokratiet....... Dens virksomhed er skjult for offentligheden, den overvåger borgernes aktiviteter, og den registrerer følsomme personoplysninger. Historien om PET rejser spørgsmålet om, hvad man skal gøre, når befolkningen i et demokrati er kritisk indstillet over for overvågningen af lovlige politiske aktiviteter......, mens myndighederne mener, at det er nødvendigt for at beskytte demokratiet. PET er på en gang en fortælling om konkrete aktioner og begivenheder i PET's arbejde og et stykke Danmarkshistorie. Det handler om overvågning, spioner, politisk ekstremisme og international terrorisme.  ...

  2. Potential of [11C]DASB for measuring endogenous serotonin with PET: binding studies

    International Nuclear Information System (INIS)

    Lundquist, Pinelopi; Wilking, Helena; Hoeglund, A. Urban; Sandell, Johan; Bergstroem, Mats; Hartvig, Per; Langstroem, Bengt

    2005-01-01

    The serotonin transporter radioligand [ 11 C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, or [ 11 C]DASB, was examined in order to assess its potential for measuring fluctuations in endogenous serotonin concentrations with positron emission tomography. Binding characteristics of [ 11 C]DASB and the propensity for serotonin to displace the tracer were explored in rat brain homogenates. Experiments showed that serotonin displaced [ 11 C]DASB in vitro. Ex vivo experiments performed after tranylcypromine injection (3 or 15 mg/kg) showed a dose-dependent trend in radioactivity uptake and suggested that serotonin may compete with [ 11 C]DASB for transporter binding

  3. N-(N-benzylpiperidin-4-yl)-2-[18F]fluorobenzamide: A potential ligand for PET imaging of σ receptors

    International Nuclear Information System (INIS)

    Shiue Chyngyann; Shiue, Grace G.; Zhang, Sue X.; Wilder, Susan; Greenberg, Joel H.; Benard, Francois; Wortman, Jeffrey A.; Alavi, Abass A.

    1997-01-01

    Four nitro- and fluorobenzamides (1-4) have been synthesized in good yields from nitro- and fluoro-substituted benzoyl chloride with 4-amino-1-benzylpiperidine. In vitro studies showed that these compounds have high affinities to σ receptors. N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide (3), in particular, bound to σ receptors with high affinity (K i = 3.4 nM, guinea pig brain membranes) and high selectivity (σ-2/σ-1 = 120). It was, therefore, labeled with 18 F and evaluated as a σ receptor radioligand. N-(N-Benzylpiperidin-4-yl)-2-[ 18 F]fluorobenzamide (3a) was synthesized in one step by nucleophilic substitution of the 2-nitro precursor (1) with [ 18 F]fluoride in DMSO at 140 deg. C for 20 min followed by purification with HPLC in 4-10% yield (decay corrected). The synthesis time was 90 min and the specific activity was 0.4-1.0 Ci/μmol. Tissue distribution in mice revealed that the uptakes of 3a in the brain, heart, liver, lungs, spleen, kidneys and small intestine were high, and the radioactivity in these organs remained constant from 60 to 120 min post-injection. The radioactivity in the bone did not significantly increase, suggesting in vivo defluorination may not be the major route of metabolism of 3a in mice. Blocking studies with haloperidol in rats indicated that the uptake of compound 3a in the rat brain was selective to haloperidol-sensitive σ sites. These results suggest that compound 3a is a potent σ receptor radioligand and may be a potential ligand for PET imaging of σ receptors in humans

  4. N-(N-benzylpiperidin-4-yl)-2-[{sup 18}F]fluorobenzamide: A potential ligand for PET imaging of {sigma} receptors

    Energy Technology Data Exchange (ETDEWEB)

    Chyngyann, Shiue; Shiue, Grace G; Zhang, Sue X; Wilder, Susan; Greenberg, Joel H; Benard, Francois; Wortman, Jeffrey A; Alavi, Abass A

    1997-10-01

    Four nitro- and fluorobenzamides (1-4) have been synthesized in good yields from nitro- and fluoro-substituted benzoyl chloride with 4-amino-1-benzylpiperidine. In vitro studies showed that these compounds have high affinities to {sigma} receptors. N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide (3), in particular, bound to {sigma} receptors with high affinity (K{sub i} = 3.4 nM, guinea pig brain membranes) and high selectivity ({sigma}-2/{sigma}-1 = 120). It was, therefore, labeled with {sup 18}F and evaluated as a {sigma} receptor radioligand. N-(N-Benzylpiperidin-4-yl)-2-[{sup 18}F]fluorobenzamide (3a) was synthesized in one step by nucleophilic substitution of the 2-nitro precursor (1) with [{sup 18}F]fluoride in DMSO at 140 deg. C for 20 min followed by purification with HPLC in 4-10% yield (decay corrected). The synthesis time was 90 min and the specific activity was 0.4-1.0 Ci/{mu}mol. Tissue distribution in mice revealed that the uptakes of 3a in the brain, heart, liver, lungs, spleen, kidneys and small intestine were high, and the radioactivity in these organs remained constant from 60 to 120 min post-injection. The radioactivity in the bone did not significantly increase, suggesting in vivo defluorination may not be the major route of metabolism of 3a in mice. Blocking studies with haloperidol in rats indicated that the uptake of compound 3a in the rat brain was selective to haloperidol-sensitive {sigma} sites. These results suggest that compound 3a is a potent {sigma} receptor radioligand and may be a potential ligand for PET imaging of {sigma} receptors in humans.

  5. Simultaneous fMRI-PET of the opioidergic pain system in human brain

    DEFF Research Database (Denmark)

    Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M

    2014-01-01

    distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET......MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically...... data were acquired with an opioid radioligand, [(11)C]diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus...

  6. Characterization of bromine-76-labelled 5-bromo-6-nitroquipazine for PET studies of the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Lundkvist, Camilla E-mail: Lundkvis@shfj.cea.fr; Loc' h, Christian; Halldin, Christer; Bottlaender, Michel; Ottaviani, Michele; Coulon, Christine; Fuseau, Chantal; Mathis, Chester; Farde, Lars; Maziere, Bernard

    1999-07-01

    The development of suitable radioligands for brain imaging of the serotonin transporter is of great importance for the study of depression and other affective disorders. The potent and selective serotonin transporter ligand, 5-iodo-6-nitro-2-piperazinylquinoline, has been labelled with iodine-123 and used as a radioligand for single photon emission computerized tomography. To evaluate the potential of the bromine-76-labelled analogue, 5-bromo-6-nitroquipazine, as a radioligand for positron emission tomography (PET), its brain distribution and binding characteristics were examined in rats. In vivo brain distribution and ex vivo autoradiography demonstrated that [{sup 76}Br]5-bromo-6-nitroquipazine enters the brain rapidly. The regional brain distribution of [{sup 76}Br]5-bromo-6-nitroquipazine was consistent with the known distribution of serotonin transporters in the midbrain, pons, thalamus, striatum, and neocortex. Specific binding was inhibited by the selective serotonin reuptake inhibitor citalopram. The peripheral metabolism in plasma was rapid, but more than 90% of the radioactivity in brain represented unchanged radioligand 2 h postinjection (p.i.). A preliminary PET study was also performed in a baboon. Following the intravenous injection of [{sup 76}Br]5-bromo-6-nitroquipazine in a baboon, there was a conspicuous accumulation of radioactivity in thalamus, striatum, and pons. The radioactivity in these brain regions was 1.5 times higher than in the cerebellum at 3 h and 2.5-4 times higher at 24 h. A rapid metabolism of the radioligand in plasma was observed (38% unchanged after 5 min). The results indicate that [{sup 76}Br]5-bromo-6-nitroquipazine has potential for PET imaging of the serotonin transporter.

  7. PET measurements od dopaminergic pathways in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Perlmutter, J.S. [Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Neurology and Neurological Surgery, Anatomy and Neurobiology; Moerlein, S.M. [Washington Univ., St. Louis, MO (United States). School of Medicine. Dept. of Biochemistry and Molecular Biophysics, Mallinckrodt Institute of Radiology

    1999-06-01

    Position emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow of metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways. Measurements of radioligand binding 'in vivo' with PET reveals abnormalities associated with specific diseases and the actions of various drugs that effect the dopaminergic system. Finally, PET measurements of the uptake of analogues of levodopa provide clues to the function of dopamine pathways potentially important for diagnosis and treatment of disease like PD.

  8. Quantitative assessment of the physical potential of proton beam range verification with PET/CT

    Science.gov (United States)

    Knopf, A.; Parodi, K.; Paganetti, H.; Cascio, E.; Bonab, A.; Bortfeld, T.

    2008-08-01

    scanner. PET/CT range verification was found to be able to detect small range modifications in the presence of complex tissue inhomogeneities. This study indicates the physical potential of the PET/CT verification method to detect the full-range characteristic of the delivered dose in the patient.

  9. Quantitative assessment of the physical potential of proton beam range verification with PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Knopf, A; Paganetti, H; Cascio, E; Bortfeld, T [Department of Radiation Oncology, MGH and Harvard Medical School, Boston, MA 02114 (United States); Parodi, K [Heidelberg Ion Therapy Center, Heidelberg (Germany); Bonab, A [Department of Radiology, MGH and Harvard Medical School, Boston, MA 02114 (United States)

    2008-08-07

    PET scanner. PET/CT range verification was found to be able to detect small range modifications in the presence of complex tissue inhomogeneities. This study indicates the physical potential of the PET/CT verification method to detect the full-range characteristic of the delivered dose in the patient.

  10. Quantitative assessment of the physical potential of proton beam range verification with PET/CT.

    Science.gov (United States)

    Knopf, A; Parodi, K; Paganetti, H; Cascio, E; Bonab, A; Bortfeld, T

    2008-08-07

    PET scanner. PET/CT range verification was found to be able to detect small range modifications in the presence of complex tissue inhomogeneities. This study indicates the physical potential of the PET/CT verification method to detect the full-range characteristic of the delivered dose in the patient.

  11. Potential impact of 68Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas

    International Nuclear Information System (INIS)

    Nyuyki, Fonyuy; Plotkin, Michail; Michel, Roger; Steffen, Ingo; Fahdt, Daniel; Brenner, Winfried; Graf, Reinhold; Denecke, Timm; Geworski, Lilli; Wurm, Reinhard

    2010-01-01

    Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with 68 Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of 68 Ga-DOTATOC-PET/CT on the definition of the ''gross tumour volume'' (GTV) in meningiomas, in order to assess the potential value of this method. Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and 68 Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV CT/MRI was 22(±19)cm 3 ; GTV PET was 23(±20)cm 3 . Additional GTV, obtained as a result of PET was 9(±10)cm 3 and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7(±11)cm 3 ). Common GTV as obtained by both CT/MRI and PET was 15(±14)cm 3 . The mean bi-directional difference between the GTV CT/MRI and GTV PET accounted to 16(±15)cm 3 (93%, p 68 Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. 68 Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas. (orig.)

  12. PET application in psychiatry and psychopharmacology

    Energy Technology Data Exchange (ETDEWEB)

    Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)

    1999-07-01

    In the last few decades diagnostic and research tools in the medical field have made great advances, yet psychiatry has lacked sufficiently sensitive tools to measure the aberration of brain functions. Recently however, the development of Positron emission tomography (PET) techniques has made it possible to measure changes in neurochemical components in mental disorders and the effect of psychoactive drugs in living human brain. Most of the advancement in the psychiatric field has came from the development psychoactive drugs. Brain research involving identification of neurotransmission is largely based on compounds developed in psychopharmacology. Some of these compounds have been radiolabelled and used as radioligands for quantitative examination of neuroreceptors and other aspects of neurotransmission. Using PET, radioligand binding can now be examined in the human brain in vivo. PET techniques also allow examination of an unlabelled drug by examination of its interaction with a radioligand. So one potential of PET in psychiatry is to investigate the mechanism of psychoactive drugs. Antidepressants modulate serotonin transmission by inhibiting serotonin reuptake from the synaptic cleft. High affinity [{sup 3}H]imipramine binding sites in mammalian brain have been labelled to investigate serotonin transporters in living human brain by PET. Cyanoimipramine which is described as a potent serotonin reuptake inhibitor, was labelled with {sup 11}C. In a PET experiment with 6 healthy human subjects, a high accumulation of [{sup 11}C]cyanoimipramine was found in the thalamus and striatum and lowest accumulation was observed in the cerebellum, a region relatively void of serotonin transporters. The thalamus to cerebellum ratio was about 2 at 90 min after the injection of the tracer. Recently, [{sup 11}C]McN5652-X has been introduced as a better tracer for serotonin transporter imaging. Employing [{sup 11}C]McN5652-X in a PET study of 7 healthy human subjects, a high

  13. PET application in psychiatry and psychopharmacology

    International Nuclear Information System (INIS)

    Suhara, Tetsuya

    1999-01-01

    In the last few decades diagnostic and research tools in the medical field have made great advances, yet psychiatry has lacked sufficiently sensitive tools to measure the aberration of brain functions. Recently however, the development of Positron emission tomography (PET) techniques has made it possible to measure changes in neurochemical components in mental disorders and the effect of psychoactive drugs in living human brain. Most of the advancement in the psychiatric field has came from the development psychoactive drugs. Brain research involving identification of neurotransmission is largely based on compounds developed in psychopharmacology. Some of these compounds have been radiolabelled and used as radioligands for quantitative examination of neuroreceptors and other aspects of neurotransmission. Using PET, radioligand binding can now be examined in the human brain in vivo. PET techniques also allow examination of an unlabelled drug by examination of its interaction with a radioligand. So one potential of PET in psychiatry is to investigate the mechanism of psychoactive drugs. Antidepressants modulate serotonin transmission by inhibiting serotonin reuptake from the synaptic cleft. High affinity [ 3 H]imipramine binding sites in mammalian brain have been labelled to investigate serotonin transporters in living human brain by PET. Cyanoimipramine which is described as a potent serotonin reuptake inhibitor, was labelled with 11 C. In a PET experiment with 6 healthy human subjects, a high accumulation of [ 11 C]cyanoimipramine was found in the thalamus and striatum and lowest accumulation was observed in the cerebellum, a region relatively void of serotonin transporters. The thalamus to cerebellum ratio was about 2 at 90 min after the injection of the tracer. Recently, [ 11 C]McN5652-X has been introduced as a better tracer for serotonin transporter imaging. Employing [ 11 C]McN5652-X in a PET study of 7 healthy human subjects, a high accumulation was observed

  14. Potential medical applications of the plasma focus in the radioisotope production for PET imaging

    International Nuclear Information System (INIS)

    Roshan, M.V.; Razaghi, S.; Asghari, F.; Rawat, R.S.; Springham, S.V.; Lee, P.; Lee, S.; Tan, T.L.

    2014-01-01

    Devices other than the accelerators are desired to be investigated for generating high energy particles to induce nuclear reaction and positron emission tomography (PET) producing radioisotopes. The experimental data of plasma focus devices (PF) are studied and the activity scaling law for External Solid Target (EST) activation is established. Based on the scaling law and the techniques to enhance the radioisotopes production, the feasibility of generating the required activity for PET imaging is studied. - Highlights: • Short lived radioisotopes for PET imaging are produced in plasma focus device. • The scaling law of the activity induced with plasma focus energy is established. • The potential medical applications of plasma focus are studied

  15. Radioligands for brain 5-HT2 receptor imaging in vivo: why do we need them?

    International Nuclear Information System (INIS)

    Busatto, G.F.

    1996-01-01

    Recently, PET and SPET radiotracers with high specificity for 5-HT 2 receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT 2 receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

  16. Evaluation of [methyl-3H]L655,708 and [ethyl-3H]RY80 as putative PET ligands for central GABAA receptors containing α5 subunit

    International Nuclear Information System (INIS)

    Opacka-Juffry, J.; Hirani, E.; Dawson, G.R.; Luthra, S.K.; Hume, S.P.

    1999-01-01

    Two selective radioligands of gamma aminobutyric acid (GABA) A receptors containing the α5 subunit, [ 3 H]L655,708 and [ 3 H]RY80, were evaluated in rats as potential in vivo tracers for positron emission tomography (PET). Brain uptake index (BUI), a measure of first pass extraction, was moderate for [ 3 H]L655,708 (BUI of 59%) and good for [ 3 H]RY80 (BUI of 96%). This finding was consistent with their in vitro binding to plasma proteins of ∼76% and 50%, respectively. Following intravenous injection of either radioligand, radioactivity in plasma was measured and uptake characteristics were assessed in brain within a time period relevant to PET scanning (up to 90 min). Discrete brain regions, such as frontal cortex, striatum, hypothalamus, thalamus, hippocampus, colliculi, medulla, and cerebellum, were sampled and the temporal distribution of radioactivity analysed. Despite the reasonable delivery to the brain, neither of the radioligands had sufficient retention in the tissues rich in α5-containing GABA A receptors to achieve a good selective signal. For both radioligands, a maximal tissue:cerebellum ratio of 1.5 was seen in hippocampus at 10 min after injection. Thus, neither of the compounds studied shows potential for further development as an in vivo PET ligand

  17. Adenocarcinoma Prostate With Neuroendocrine Differentiation: Potential Utility of 18F-FDG PET/CT and 68Ga-DOTANOC PET/CT Over 68Ga-PSMA PET/CT.

    Science.gov (United States)

    Parida, Girish Kumar; Tripathy, Sarthak; Datta Gupta, Shreya; Singhal, Abhinav; Kumar, Rakesh; Bal, Chandrasekhar; Shamim, Shamim Ahmed

    2018-04-01

    Ga-PSMA PET/CT is the upcoming imaging modality for staging, restaging and response assessment of prostate cancer. However, due to neuroendocrine differentiation in some of patients with prostate cancer, they express somatostatin receptors instead of prostate specific membrane antigen. This can be exploited and other modalities like Ga-DOTANOC PET/CT and F-FDG PET/CT should be used in such cases for guiding management. We hereby discuss a similar case of 67-year-old man of adenocarcinoma prostate with neuroendocrine differentiation, which shows the potential pitfall of Ga-PSMA PET/CT imaging and benefit of Ga-DOTANOC PET/CT and F-FDG PET/CT in such cases.

  18. The degradation potential of PET bottles in the marine environment: An ATR-FTIR based approach

    Science.gov (United States)

    Ioakeimidis, C.; Fotopoulou, K. N.; Karapanagioti, H. K.; Geraga, M.; Zeri, C.; Papathanassiou, E.; Galgani, F.; Papatheodorou, G.

    2016-03-01

    The dominance and persistence of plastic debris in the marine environment are well documented. No information exists in respect to their lifespan in the marine environment. Nevertheless, the degradation potential of plastic litter items remains a critical issue for marine litter research. In the present study, polyethylene terephthalate bottles (PETs) collected from the submarine environment were characterized using ATR-FTIR in respect to their degradation potential attributed to environmental conditions. A temporal indication was used as indicative to the years of presence of the PETs in the environment as debris. PETs seem to remain robust for approximately fifteen years. Afterwards, a significant decrease of the native functional groups was recorded; some even disappear; or new-not typical for PETs-are created. At a later stage, using the PET time series collected from the Saronikos Gulf (Aegean Sea-E. Mediterranean), it was possible to date bottles that were collected from the bottom of the Ionian Sea (W. Greece). It is the first time that such a study has been conducted with samples that were actually degraded in the marine environment.

  19. Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru [Hunan Institute of Engineering, Hunan Xiangtan (China). College of Chemistry and Chemical Engineering; Xia, Jiao-yun [Changsha Univ. of Science and Technology (China). School of Chemistry and Biology Engineering

    2016-07-01

    The dopamine D{sub 4} receptor has been shown to play important roles in some central nervous system pathologies. Specific radioligands for the D{sub 4} receptor may be useful to understand the function of the D{sub 4} receptor and its correlations with various disorders. 2-(3-(4-(4-[{sup 18}F]Fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole ([{sup 18}F]4) was synthesized through a one-pot two-step procedure with total yield 18.6% (decay corrected). The specific activity of the radioligand was 112 GBq/μmol and its radiochemical purity was >95.0%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding evaluation and the K{sub i} value for the D{sub 4} receptor was determined to be 2.9±0.2 nM, and its selectivity for the dopamine D{sub 4} receptor is 709-fold versus D{sub 2long} receptor, 823-fold versus D{sub 3} receptor. The partition coefficient (Log D) of it was determined to be 2.6±0.1 through octanol-water partition experiment. The ligand presents desirable combination of lipophilicity, affinity and selectivity for the dopamine D{sub 4} receptor. The results suggested that the radioligand shows promises for the in vivo study of the dopamine D{sub 4} receptor.

  20. Clinical impact of Positron Emission Tomography (PET) on oncological patients and their potentially application context

    International Nuclear Information System (INIS)

    Alonso, O.

    2006-01-01

    (PET) Positron Emission Tomography is a technique of nuclear medicine that has ability of detecting cancer through mechanisms based on molecular alterations of neoplastic processes. This review describes the PET Oncology applications and discusses the potential application of this technology in the sanitary and national academic framework . The most widely used in Oncology plotter is an analogue of laglucosa labelled with fluo: 18F-2-fluoro-2-Deoxy-D-glucose (FDG). In this way, the PET detects tumour retention of FDG, due to the highest glycolytic of cancer cells. In addition, the PET allow the study of the entire body at the same exploratory and some teams are coupled to systems of axial tomography (PET-CT). By ET-FDG, it is possible to diagnose, staging and restaged the majority of cancers, with diagnostic accuracy close to 90 per cent higher than the values provided by the conventional imaging techniques such. It is also possible to know early response to cancer treatments and obtain relevant medical prognosis information. (author) [es

  1. Potential for PET scanning as an aid to heat transfer modeling

    International Nuclear Information System (INIS)

    Samulski, T.V.; Harris, C.; Winget, J.M.; Dewhirst, M.W.

    1987-01-01

    Positron Emission Tomography (PET) using /sup 68/Ga labelled microspheres (15μ diam.) for quantitative imaging of perfusion is being investigated for its potential to aid in verification of parameter estimation techniques. Such techniques have been used in bioheat transfer modeling where direct measurement of perfusion has not been possible. Perfusion is needed, to utilize bioheat transfer to predict temperatures between measured points during hyperthermia therapy. A preliminary study showing that PET could be used for verification of parameter estimation was done by heating a melanoma in a dog in which multiple thermometry catheters were placed in a central plane. Microspheres were injected at the end of a one hour heat treatment session before power down. CT and PET images of the same plane were aligned so that relative counts/pixel in 2 cm regions of interest of the PET image were measured along several catheter tracks. In all tracks measured an inverse correlation was shown between relative perfusion and temperature along the catheter during thermal steady state. These data strongly imply that PET scans obtained in the manner described bear relevance to bioheat transfer and for verification of perfusion in heated tissues as estimated by heat transfer modeling

  2. Potential of hybrid 18F-fluorocholine PET/MRI for prostate cancer imaging

    International Nuclear Information System (INIS)

    Perrot, Thomas de; Scheffler, Max; Vallee, Jean-Paul; Rager, Olivier; Ratib, Osman; Lord, Martin; Pusztaszeri, Marc; Iselin, Christophe

    2014-01-01

    To report the first results of hybrid 18 F-fluorocholine PET/MRI imaging for the detection of prostate cancer. This analysis included 26 consecutive patients scheduled for prostate PET/MRI before radical prostatectomy. The examinations were performed on a hybrid whole-body PET/MRI scanner. The MR acquisitions which included T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences were followed during the same session by whole-body PET scans. Parametric maps were constructed to measure normalized T2-weighted intensity (nT2), apparent diffusion coefficient (ADC), volume transfer constant (K trans ), extravascular extracellular volume fraction (v e ) and standardized uptake values (SUV). With pathology as the gold standard, ROC curves were calculated using logistic regression for each parameter and for the best combination with and without PET to obtain a MR model versus a PETMR model. Of the 26 patients initially selected, 3 were excluded due to absence of an endorectal coil (2 patients) or prosthesis artefacts (1 patient). In the whole prostate, the area under the curve (AUC) for SUV max , ADC, nT2, K trans and v e were 0.762, 0.756, 0.685, 0.611 and 0.529 with a best threshold at 3.044 for SUV max and 1.075 x 10 -3 mm 2 /s for ADC. The anatomical distinction between the transition zone and the peripheral zone showed the potential of the adjunctive use of PET. In the peripheral zone, the AUC of 0.893 for the PETMR model was significantly greater (p = 0.0402) than the AUC of 0.84 for the MR model only. In the whole prostate, no relevant correlation was observed between ADC and SUV max . The SUV max was not affected by the Gleason score. The performance of a hybrid whole-body 18 F-fluorocholine PET/MRI scan in the same session combined with a prostatic MR examination did not interfere with the diagnostic accuracy of the MR sequences. The registration of the PET data and the T2 anatomical MR sequence data allowed precise localization of hypermetabolic

  3. Potential of hybrid {sup 18}F-fluorocholine PET/MRI for prostate cancer imaging

    Energy Technology Data Exchange (ETDEWEB)

    Perrot, Thomas de; Scheffler, Max; Vallee, Jean-Paul [Geneva University Hospitals and University of Geneva, Division of Radiology, Geneve 14 (Switzerland); Rager, Olivier; Ratib, Osman [Geneva University Hospitals, Division of Nuclear Medicine, Geneva (Switzerland); Lord, Martin [University of Montreal Hospital Center, Division of Nuclear Medicine, Montreal (Canada); Pusztaszeri, Marc [Geneva University Hospitals, Division of Clinical Pathology, Geneva (Switzerland); Iselin, Christophe [Geneva University Hospitals, Division of Urologic Surgery, Geneva (Switzerland)

    2014-09-15

    To report the first results of hybrid {sup 18}F-fluorocholine PET/MRI imaging for the detection of prostate cancer. This analysis included 26 consecutive patients scheduled for prostate PET/MRI before radical prostatectomy. The examinations were performed on a hybrid whole-body PET/MRI scanner. The MR acquisitions which included T2-weighted, diffusion-weighted and dynamic contrast-enhanced sequences were followed during the same session by whole-body PET scans. Parametric maps were constructed to measure normalized T2-weighted intensity (nT2), apparent diffusion coefficient (ADC), volume transfer constant (K {sup trans}), extravascular extracellular volume fraction (v{sub e}) and standardized uptake values (SUV). With pathology as the gold standard, ROC curves were calculated using logistic regression for each parameter and for the best combination with and without PET to obtain a MR model versus a PETMR model. Of the 26 patients initially selected, 3 were excluded due to absence of an endorectal coil (2 patients) or prosthesis artefacts (1 patient). In the whole prostate, the area under the curve (AUC) for SUV{sub max}, ADC, nT2, K {sup trans} and v{sub e} were 0.762, 0.756, 0.685, 0.611 and 0.529 with a best threshold at 3.044 for SUV{sub max} and 1.075 x 10{sup -3} mm{sup 2}/s for ADC. The anatomical distinction between the transition zone and the peripheral zone showed the potential of the adjunctive use of PET. In the peripheral zone, the AUC of 0.893 for the PETMR model was significantly greater (p = 0.0402) than the AUC of 0.84 for the MR model only. In the whole prostate, no relevant correlation was observed between ADC and SUV{sub max}. The SUV{sub max} was not affected by the Gleason score. The performance of a hybrid whole-body {sup 18}F-fluorocholine PET/MRI scan in the same session combined with a prostatic MR examination did not interfere with the diagnostic accuracy of the MR sequences. The registration of the PET data and the T2 anatomical MR

  4. Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands.

    Science.gov (United States)

    Taylor, Nicholas J; Emer, Enrico; Preshlock, Sean; Schedler, Michael; Tredwell, Matthew; Verhoog, Stefan; Mercier, Joel; Genicot, Christophe; Gouverneur, Véronique

    2017-06-21

    Molecules labeled with fluorine-18 ( 18 F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18 F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18 F-fluorination of aryl boron reagents with 18 F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18 F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

  5. Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients

    International Nuclear Information System (INIS)

    Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer; Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel; Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars; Eriksdotter, Maria; Freund-Levi, Yvonne; Jeppsson, Fredrik

    2013-01-01

    The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [ 11 C]AZD2995 and [ 11 C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [ 3 H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [ 11 C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [ 11 C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [ 11 C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [ 11 C]AZD2995. However, the very low nonspecific binding of [ 11 C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)

  6. The 5-HT1A Receptor PET Radioligand 11C-CUMI-101 Has Significant Binding to α1-Adrenoceptors in Human Cerebellum, Limiting Its Use as a Reference Region.

    Science.gov (United States)

    Shrestha, Stal S; Liow, Jeih-San; Jenko, Kimberly; Ikawa, Masamichi; Zoghbi, Sami S; Innis, Robert B

    2016-12-01

    Prazosin, a potent and selective α 1 -adrenoceptor antagonist, displaces 25% of 11 C-CUMI-101 ([O-methyl- 11 C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione) binding in monkey cerebellum. We sought to estimate the percentage contamination of 11 C-CUMI-101 binding to α 1 -adrenoceptors in human cerebellum under in vivo conditions. In vitro receptor-binding techniques were used to measure α 1 -adrenoceptor density and the affinity of CUMI-101 for these receptors in human, monkey, and rat cerebellum. Binding potential (maximum number of binding sites × affinity [(1/dissociation constant]) was determined using in vitro homogenate binding assays in human, monkey, and rat cerebellum. 3 H-prazosin was used to determine the maximum number of binding sites, as well as the dissociation constant of 3 H-prazosin and the inhibition constant of CUMI-101. α 1 -adrenoceptor density and the affinity of CUMI-101 for these receptors were similar across species. Cerebellar binding potentials were 3.7 for humans, 2.3 for monkeys, and 3.4 for rats. Reasoning by analogy, 25% of 11 C-CUMI-101 uptake in human cerebellum reflects binding to α 1 -adrenoceptors, suggesting that the cerebellum is of limited usefulness as a reference tissue for quantification in human studies. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  7. Synthesis of [{sup 11}C]-S21007 a novel 5HT{sub 3} partial agonist as a potential tracer for PET studies

    Energy Technology Data Exchange (ETDEWEB)

    Guillouet, S.; Barre, L.; Gourand, F. [CEA Centre de Cyceron, 14 -Caen (France); Lasne, M.C. [Centre National de la Recherche Scientifique, 14 - Caen (France); Rault, S. [Caen Univ., 14 (France). Faculte de Pharmacie

    1996-04-01

    5HT{sub 3} receptors have been the focus of much research during the last decade. The presence of these receptors has been demonstrated in many neuronal tissues, both in periphery and in the CNS. The identification of selective agonists and antagonists for this receptor subtype has allowed the discovery of several important new therapeutic applications as the inhibition of pain, migraine, cytotoxic and radiation-induced emesis and treatment of psychoses and anxiety. The first 5HT{sub 3} antagonist labelled with a {beta}+ emitter atom was [{sup 11}C]MDL72222. The PET studies which have been performed with it in the brain of baboon (distribution, kinetics and binding) have established that it was not a good radioligand to detect a specific binding, due to its high lipophilicity. Other radioligands have been developed since, but their affinities for 5HT{sub 3} receptors PET studies have not been demonstrated. Among a series of of tricyclic piperazine derivatives synthesized, S21007 has been described as a novel selective and partial agonist which possesses a good affinity for 5HT{sub 3} receptors (IC{sub 50} = 1nM) versus other 5HT subtypes studied where IC{sub 50} > 1{mu}M. We report here the radiosynthesis of [{sup 11}C]S21007. (author).

  8. Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012

    Directory of Open Access Journals (Sweden)

    Susann Schröder

    2016-05-01

    Full Text Available Cyclic nucleotide phosphodiesterases (PDEs are a class of intracellular enzymes that inactivate the secondary messenger molecules, cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP. Thus, PDEs regulate the signaling cascades mediated by these cyclic nucleotides and affect fundamental intracellular processes. Pharmacological inhibition of PDE activity is a promising strategy for treatment of several diseases. However, the role of the different PDEs in related pathologies is not completely clarified yet. PDE-specific radioligands enable non-invasive visualization and quantification of these enzymes by positron emission tomography (PET in vivo and provide an important translational tool for elucidation of the relationship between altered expression of PDEs and pathophysiological effects as well as (pre-clinical evaluation of novel PDE inhibitors developed as therapeutics. Herein we present an overview of novel PDE radioligands for PET published since 2012.

  9. In vivo evaluation of [{sup 11}C]N-(2-chloro-5-thiomethylphenyl)-N'- (3-methoxy-phenyl)-N'-methylguanidine ([{sup 11}C]GMOM) as a potential PET radiotracer for the PCP/NMDA receptor

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. E-mail: rnw7@columbia.edu; Slifstein, Mark; Dumont, Filip; Zhao Jun; Chang, Raymond C.; Sudo, Yasuhiko; Sultana, Abida; Balter, Andrew; Laruelle, Marc

    2004-10-01

    The development of imaging methods to measure changes in NMDA ion channel activation would provide a powerful means to probe the mechanisms of drugs and device based treatments (e.g., ECT) thought to alter glutamate neurotransmission. To provide a potential NMDA/PCP receptor PET tracer, we synthesized the radioligand [{sup 11}C]GMOM (K{sub i} = 5.2 {+-}0.3 nM; log P = 2.34) and evaluated this ligand in vivo in awake male rats and isoflurane anesthetized baboons. In rats, the regional brain uptake of [{sup 11}C]GMOM ranged from 0.75{+-}0.13% ID/g in the medulla and pons to 1.15{+-}0.17% ID/g in the occipital cortex. MK801 (1 mg/kg i.v.) significantly reduced (24-28%) [{sup 11}C]GMOM uptake in all regions. D-serine (10 mg/kg i.v.) increased [{sup 11}C]GMOM %ID/g values in all regions (10-24%) reaching significance in the frontal cortex and cerebellum only. The NR2B ligand RO 25-6981 (10 mg/kg i.v.) reduced [{sup 11}C]GMOM uptake significantly (24-38%) in all regions except for the cerebellum and striatum. Blood activity was 0.11{+-}0.03 %ID/g in the controls group and did not vary significantly across groups. PET imaging in isoflurane-anesthetized baboons with high specific activity [{sup 11}C]GMOM provided fairly uniform regional brain distribution volume (V{sub T}) values (12.8-17.1 ml g{sup -1}). MK801 (0.5 mg/kg, i.v., n = 1, and 1.0 mg/kg, i.v., n = 1) did not significantly alter regional V{sub T} values, indicating a lack of saturable binding. However, the potential confounding effects associated with ketamine induction of anesthesia along with isoflurane maintenance must be considered because both agents are known to reduce NMDA ion channel activation. Future and carefully designed studies, presumably utilizing an optimized NMDA/PCP site tracer, will be carried out to further explore these hypotheses. We conclude that, even though [{sup 11}C]GMOM is not an optimized PCP site radiotracer, its binding is altered in vivo in awake rats as expected by modulation of

  10. Quantitative and Visual Assessments toward Potential Sub-mSv or Ultrafast FDG PET Using High-Sensitivity TOF PET in PET/MRI.

    Science.gov (United States)

    Behr, Spencer C; Bahroos, Emma; Hawkins, Randall A; Nardo, Lorenzo; Ravanfar, Vahid; Capbarat, Emily V; Seo, Youngho

    2018-06-01

    Newer high-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability to preserve diagnostic image quality with low count density, while maintaining a high raw photon detection sensitivity that would allow for a reduction in injected dose or rapid data acquisition. To assess this, we performed quantitative and visual assessments of the PET images acquired using a highly sensitive (23.3 cps/kBq) large field of view (25-cm axial) silicon photomultiplier (SiPM)-based TOF PET (400-ps timing resolution) integrated with 3 T-MRI in comparison to PET images acquired on non-TOF PET/x-ray computed tomography (CT) systems. Whole-body 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) PET/CT was acquired for 15 patients followed by whole body PET/magnetic resonance imaging (MRI) with an average injected dose of 325 ± 84 MBq. The PET list mode data from PET/MRI were reconstructed using full datasets (4 min/bed) and reduced datasets (2, 1, 0.5, and 0.25 min/bed). Qualitative assessment between PET/CT and PET/MR images were made. A Likert-type scale between 1 and 5, 1 for non-diagnostic, 3 equivalent to PET/CT, and 5 superior quality, was used. Maximum and mean standardized uptake values (SUV max and SUV mean ) of normal tissues and lesions detected were measured and compared. Mean visual assessment scores were 3.54 ± 0.32, 3.62 ± 0.38, and 3.69 ± 0.35 for the brain and 3.05 ± 0.49, 3.71 ± 0.45, and 4.14 ± 0.44 for the whole-body maximum intensity projections (MIPs) for 1, 2, and 4 min/bed PET/MR images, respectively. The SUV mean values for normal tissues were lower and statistically significant for images acquired at 4, 2, 1, 0.5, and 0.25 min/bed on the PET/MR, with values of - 18 ± 28 % (p PET/MR datasets. High-sensitivity TOF PET showed comparable but still better visual image quality even at a much reduced activity in comparison to lower-sensitivity non-TOF PET. Our data translates to a seven times

  11. Potential impact of {sup 68}Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Nyuyki, Fonyuy; Plotkin, Michail; Michel, Roger; Steffen, Ingo; Fahdt, Daniel; Brenner, Winfried [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Graf, Reinhold [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Denecke, Timm [Charite-Universitaetsmedizin Berlin, Department for Radiology, Campus Virchow, Berlin (Germany); Geworski, Lilli [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Medizinische Hochschule Hannover, Department for Radiation Safety and Medical Physics, Hannover (Germany); Wurm, Reinhard [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Klinikum Frankfurt (Oder), Department for Radiation Therapy and Radiooncology, Frankfurt (Germany)

    2010-02-15

    Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with {sup 68}Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of {sup 68}Ga-DOTATOC-PET/CT on the definition of the ''gross tumour volume'' (GTV) in meningiomas, in order to assess the potential value of this method. Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and {sup 68}Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV{sub CT/MRI} was 22({+-}19)cm{sup 3}; GTV{sub PET} was 23({+-}20)cm{sup 3}. Additional GTV, obtained as a result of PET was 9({+-}10)cm{sup 3} and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7({+-}11)cm{sup 3}). Common GTV as obtained by both CT/MRI and PET was 15({+-}14)cm{sup 3}. The mean bi-directional difference between the GTV{sub CT/MRI} and GTV{sub PET} accounted to 16({+-}15)cm{sup 3} (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. {sup 68}Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration

  12. Radioligands for brain 5-HT{sub 2} receptor imaging in vivo: why do we need them?

    Energy Technology Data Exchange (ETDEWEB)

    Busatto, G.F. [Section of Clinical Neuropharmacology, Dept. of Psychological Medicine, Inst. of Psychiatry, London (United Kingdom)

    1996-08-01

    Recently, PET and SPET radiotracers with high specificity for 5-HT{sub 2} receptors have been developed. These have been studied in baboons and humans with promising results, displaying a binding profile compatible with the brain distribution of 5-HT{sub 2} receptors. It is predicted that studies with the newly developed 5-HT radioligands will substantially increase knowledge about the pharmacology of brain disorders. (orig./MG)

  13. PET studies of potential chemotherapeutic agents: Pt. 10

    International Nuclear Information System (INIS)

    Conway, T.; Diksic, M.; McGill Univ., Montreal, PQ

    1991-01-01

    Carbon-11-labeled HECNU [1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea] a potential chemotherapeutic agent, has been prepared by the nitrosation of the corresponding carbon-11-labeled urea, HECU, [1-(2-chloroethyl)-3-(2-hydroxyethyl) urea]. The isomeric byproduct of nitrosation, 1-(2-chloroethyl)-3-nitroso-3-(2-hydroxyethyl) urea can be efficiently removed by preparative scale HPLC on a Partisil column. ( 11 C)-HECU was prepared by reacting ethanolamine with ( 11 C)-2-chloroethyl-isocyanate which was itself prepared by reacting ( 11 C)-phosgene with 2-chloroethylamine hydrochloride suspended in dioxane at 60-65 o C. This synthesis yielded ( 11 C)-HECNU with an average radiochemical purity of 98% in an average radiochemical yield of 18% relative to the radioactivity measured at the end of the 11 C-phosgene introduction. (author)

  14. Radioligand purification prior to routine receptor assays

    International Nuclear Information System (INIS)

    Le Goff, J.-M.; Berthois, Y.; Martin, P.-M.

    1988-01-01

    The need to repurify the commercially available radioligands [ 3 H]estradiol and [ 3 H]testosterone before use in routine assays was investigated. Storage of these products for 2 months after delivery led to appreciable degradation of [ 3 H]estradiol compared to [ 3 H]testosterone. Unexpectedly, TLC and even HPLC procedures were ineffective in completely restoring the purity of [ 3 H]-estradiol and the unremoved polar products induced important variations in our estrogen receptor assays. An increase in non-specific binding and a concomitant decrease in total binding were observed resulting in an underestimation of specific binding sites and of the affinity constant. In some cases Scatchard analysis was not possible. The authors therefore strongly recommend the repurification of low-stability radioligands and propose an economic time-saving procedure for the purification of [ 3 H]estradiol by solvent differential partition which requires no high-cost investment in apparatus. (author)

  15. Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael R; Frey, Kirk A; Vander Borght, Thierry; Sherman, Phillip S

    1996-05-01

    The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([{sup 11}C]dihydrotetrabenazine and [{sup 11}C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

  16. Potential enterotoxicity and antimicrobial resistance pattern of Aeromonas species isolated from pet turtles and their environment.

    Science.gov (United States)

    Wimalasena, S H M P; Shin, Gee-Wook; Hossain, Sabrina; Heo, Gang-Joon

    2017-05-23

    To investigate the potential enterotoxicity and antimicrobial resistance of aeromonads from pet turtles as a risk for human infection, one hundred and two Aeromonas spp. were isolated from the feces, skin and rearing environments of pet turtles and identified by biochemical and gyrB sequence analyses. Aeromonas enteropelogenes was the predominant species among the isolates (52.9%) followed by A. hydrophila (32.4%), A. dharkensis (5.9%), A. veronii (4.9%) and A. caviae (3.9%). Their potential enterotoxicities were evaluated by PCR assays for detecting genes encoding cytotoxic enterotoxin (act) and two cytotonic enterotoxins (alt and ast). 75.8% of A. hydrophila isolates exhibited the act + /alt + /ast + genotype, whereas 94.4% of A. enteropelogenes isolates were determined to be act - /alt - /ast - . In an antimicrobial susceptibility test, most isolates were susceptible to all tested antibiotics except amoxicillin, ampicillin, cephalothin, chloramphenicol and tetracycline. Non-susceptible isolates to penicillins (ampicillin and amoxicillin) and fluoroquinolones (ciprofloxacin and norfloxacin) were frequently observed among the A. enteropelogenes isolates. Few isolates were resistant to imipenem, amikacin, ceftriaxone and cefotaxime. Collectively, these results suggest that pet turtles may pose a public health risk of infection by enterotoxigenic and antimicrobial resistant Aeromonas strains.

  17. Synthesis and evaluation of 1-[l brace]1-[5-(2'-[[sup 18]F]fluoroethyl)-2-thienyl]cyclohexyl[r brace]piperidine as a potential in vivo radioligand for the NMDA receptor-channel complex. [N-methyl-D-aspartate receptor

    Energy Technology Data Exchange (ETDEWEB)

    Orita, Kazuhiro; Sasaki, Shigeki; Maeda, Minoru [Kyushu Univ., Fukuoka (Japan). Faculty of Pharmaceutical Sciences; Hashimoto, Atsushi; Nishikawa, Toru [National Inst. of Neuroscience, Tokyo (Japan); Yugami, Tomoko; Umezu, Kohei [Mitsubishi Kasei Corp., Yokohama (Japan). Research Center

    1993-10-01

    1-[l brace]1-[5-(2'-[[sup 18]F]Fluoroethyl)-2-thienyl]cyclohexyl[r brace]piperidine ([sup 18]FE-TCP) was prepared a fluorine-substituted analogue of the potent NMDA receptor channel blocker, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), by the mesylate displacement with [[sup 18]F]fluoride ion with isolated radiochemical yields of 6-12%, and the synthesis time including a two step HPLC purification was 120 min. The regional distribution in rat brain after i.v. injection of [sup 18]FE-TCP was heterogeneous and similar to the known distribution of phencyclidine recognition sites, with hippocampus-cerebellum, striatum-cerebellum and cerebral cortex-cerebellum concentration ratios of 2.08, 1.7 and 1.54, respectively, 15 min post-injection. Furthermore, this localized regional cerebral distribution was blocked by co-injection with the unlabelled FE-TCP or pretreatment with cis-2-hydroxymethyl-r-1-(N-piperidyl)-1-(2-thienyl)cyclohexane, with the greatest reductions seen in the hippocampus followed by the striatum and cerebral cortex. However, relatively low receptor binding affinity and high non-specific binding due to its high lipophilicity suggest that [sup 18]FE-TCP may not be a suitable radioligand for in vivo PET investigations of the NMDA receptor-channel complex. (Author).

  18. Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers.

    Science.gov (United States)

    Cho, Jongmin; Wang, Min; Gonzalez-Lepera, Carlos; Mawlawi, Osama; Cho, Sang Hyun

    2016-08-01

    . The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.

  19. Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jongmin, E-mail: jongmin.cho@okstate.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Wang, Min [Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Gonzalez-Lepera, Carlos [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Cho, Sang Hyun [Departments of Radiation Physics and Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States)

    2016-08-15

    signals from mostly decaying {sup 66}Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated. Conclusions: The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.

  20. Low background and high contrast PET imaging of amyloid-{beta} with [{sup 11}C]AZD2995 and [{sup 11}C]AZD2184 in Alzheimer's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Forsberg, Anton; Andersson, Jan; Varnaes, Katarina; Halldin, Christer [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Jureus, Anders; Swahn, Britt-Marie; Sandell, Johan; Julin, Per; Svensson, Samuel [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Cselenyi, Zsolt; Schou, Magnus; Johnstroem, Peter; Farde, Lars [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska Hospital, AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Eriksdotter, Maria; Freund-Levi, Yvonne [Karolinska Institutet, Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Stockholm (Sweden); Karolinska University Hospital, Department of Geriatric Medicine, Stockholm (Sweden); Jeppsson, Fredrik [AstraZeneca Research and Development, Neuroscience Research and Therapy Area, Soedertaelje (Sweden); Karolinska Institutet, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Stockholm (Sweden)

    2013-04-15

    The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-{beta} in Alzheimer's disease (AD). In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-{beta} PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [{sup 11}C]AZD2995 and [{sup 11}C]AZD2184 in three healthy control subjects and seven AD patients. AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-{beta}. [{sup 3}H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [{sup 11}C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [{sup 11}C]AZD2995 was greater in areas with lower amyloid-{beta} load, e.g. the hippocampus. Both AZD2995 and AZD2184 detect amyloid-{beta} with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [{sup 11}C]AZD2184 seems to be an amyloid-{beta} radioligand with higher uptake and better group separation when compared to [{sup 11}C]AZD2995. However, the very low nonspecific binding of [{sup 11}C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-{beta}. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy. (orig.)

  1. 11C-harmine as a potential PET tracer for ductal pancreas cancer: in vitro studies

    International Nuclear Information System (INIS)

    Herlin, G.; Persson, B.; Laangstroem, B.; Aspelin, P.; Bergstroem, M.

    2003-01-01

    Our objective was to find a tracer in diagnosing human pancreatic cancer using positron emission tomography (PET). For this purpose in vitro test of pancreatic tissues with autoradiography was used. Autoradiography was performed with 11 C-harmine (a MAO-A-inhibitor) with and without competitive inhibition. Tissue preparations were obtained from normal human pancreas and pancreatic cancer. The uptake was compared with rat brain or pig brain, tissues with high expression of MAO-A. Nine autoradiography studies on 16 samples from five different human pancreatic cancers gave a significant level of specific binding of 11 C-harmine in 13, and 3 samples did not give a significant level of specific binding of 11 C-harmine. All 16 samples were analysed with autoradiography. Compared with rat brain, the uptake in the human cancers varied between 9 and 43% except for one tissue preparation which had a too low value for measurement. This study shows expression of MAO-A in human pancreatic cancer. This is readily characterised in vitro. The potential use of 11 C-harmine in the diagnosis of pancreatic cancer using PET might be limited, but further PET studies are necessary. (orig.)

  2. Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

    International Nuclear Information System (INIS)

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

    2010-01-01

    Introduction: Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis. Methods: [ 18 F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 deg. C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results: In vitro stability studies demonstrated that [ 18 F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but 18 F-labeled rhodamines should accumulate in the heart. Conclusions: [ 18 F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18 F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

  3. Cryptosporidium spp. in pet birds: genetic diversity and potential public health significance.

    Science.gov (United States)

    Qi, Meng; Wang, Rongjun; Ning, Changshen; Li, Xiaoyu; Zhang, Longxian; Jian, Fuchun; Sun, Yanru; Xiao, Lihua

    2011-08-01

    To characterize the prevalence and assess the zoonotic transmission burden of Cryptosporidium species/genotypes in pet birds in Henan, China, 434 fecal samples were acquired from 14 families of birds in pet shops. The overall prevalence of Cryptopsoridium was 8.1% (35/434) by the Sheather's sugar flotation technique. The Cryptosporidium-positive samples were analyzed by DNA sequence analysis of the small subunit (SSU) rRNA gene. Three Cryptosporidium species and two genotypes were identified, including C. baileyi (18/35 or 51.4%) in five red-billed leiothrixes (Leiothrix lutea), four white Java sparrows (Padda oryzivora), four common mynas (Acridotheres tristis), two zebra finches (Taeniopygia guttata), a crested Lark (Galerida cristata), a Gouldian finch (Chloebia gouldiae), and a black-billed magpie (Pica pica); Cryptosporidium meleagridis (3/35 or 8.6%) in a Bohemian waxwing (Bombycilla garrulus), a Rufous turtle dove (Streptopelia orientalis), and a fan-tailed pigeon (Columba livia); Cryptosporidium galli (5/35 or 14.3%) in four Bohemian waxwings (Bombycilla garrulus) and a silver-eared Mesia (Leiothrix argentauris); Cryptosporidium avian genotype III (3/35 or 8.6%) in two cockatiels (Nymphicus hollandicus) and a red-billed blue magpie (Urocissa erythrorhyncha); and Cryptosporidium avian genotype V (6/35 or 17.1%) in six cockatiels (Nymphicus hollandicus). Among the pet birds, 12 species represented new hosts for Cryptosporidum infections. The presence of C. meleagridis raises questions on potential zoonotic transmission of cryptosporidiosis from pet birds to humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. In vitro and in vivo evaluation of [11C]MPEPy as a potential PET ligand for mGlu5 receptors

    International Nuclear Information System (INIS)

    Severance, Alin J.; Parsey, Ramin V.; Kumar, J.S. Dileep; Underwood, Mark D.; Arango, Victoria; Majo, Vattoly J.; Prabhakaran, Jaya; Simpson, Norman R.; Heertum, Ronald L. van; Mann, J. John

    2006-01-01

    Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR 5 ) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR 5 radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR 5 receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [ 11 C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [ 11 C]MPEPy as a PET radiotracer in humans

  5. Visual evaluation of kinetic characteristics of PET probe for neuroreceptors using a two-phase graphic plot analysis.

    Science.gov (United States)

    Ito, Hiroshi; Ikoma, Yoko; Seki, Chie; Kimura, Yasuyuki; Kawaguchi, Hiroshi; Takuwa, Hiroyuki; Ichise, Masanori; Suhara, Tetsuya; Kanno, Iwao

    2017-05-01

    Objectives In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compartment model (2-TCM), and binding parameters, including the total distribution volume (V T ), non-displaceable distribution volume (V ND ), and binding potential (BP ND ), can be determined from model parameters estimated by kinetic analysis. The stability of binding parameter estimates depends on the kinetic characteristics of radioligands. To describe these kinetic characteristics, we previously developed a two-phase graphic plot analysis in which V ND and V T can be estimated from the x-intercept of regression lines for early and delayed phases, respectively. In this study, we applied this graphic plot analysis to visual evaluation of the kinetic characteristics of radioligands for neuroreceptors, and investigated a relationship between the shape of these graphic plots and the stability of binding parameters estimated by the kinetic analysis with 2-TCM in simulated brain tissue time-activity curves (TACs) with various binding parameters. Methods 90-min TACs were generated with the arterial input function and assumed kinetic parameters according to 2-TCM. Graphic plot analysis was applied to these simulated TACs, and the curvature of the plot for each TAC was evaluated visually. TACs with several noise levels were also generated with various kinetic parameters, and the bias and variation of binding parameters estimated by kinetic analysis were calculated in each TAC. These bias and variation were compared with the shape of graphic plots. Results The graphic plots showed larger curvature for TACs with higher specific binding and slower dissociation of specific binding. The quartile deviations of V ND and BP ND determined by kinetic analysis were smaller for radioligands with slow dissociation. Conclusions The larger curvature of graphic plots for radioligands with slow dissociation might indicate a stable determination of V ND and BP ND by kinetic analysis. For

  6. Radioligand assay for biotin in liver tissues

    International Nuclear Information System (INIS)

    Rettenmaier, R.

    1979-01-01

    A radioligand assay for biotin in liver tissue is described. 3 H-biotin is used as tracer and avidin as binder. The biotin-loaded avidin is separated from free biotin on dextran-coated charcoal, which leaves the avidin-biotin complex in the supernatant liquid. Thus, the avidin-biotin complex can easily be utilized for determination of the radioactivity. Calibration with known additions of biotin in the range 0.25-8.0 ng per assay sample yields a linear logit-log plot. The biotin is extracted from liver tissues by enzymatic proteolysis with papain. This treatment is optimized to liberate the bound forms of the vitamin. Microbiological parallel assays with Lactobacillus plantarum were in good agreement with the radioligand assay giving a regression coefficient of 0.974(n=44). The coefficient of variation was found to be 4.2% in the range 500-1200 ng of biotin per g of liver tissue (n=46). The method is simple and reliable and allows the simultaneous analysis of a considerable number of samples. (Auth.)

  7. Preclinical evaluation of an 18F-labelled beta1-adrenoceptor selective radioligand based on ICI 89,406.

    Science.gov (United States)

    Law, Marilyn P; Wagner, Stefan; Kopka, Klaus; Renner, Christiane; Pike, Victor W; Schober, Otmar; Schäfers, Michael

    2010-05-01

    Radioligand binding studies indicate a down-regulation of myocardial beta(1)-adrenoceptors (beta(1)-AR) in cardiac disease which may or may not be associated with a decrease in beta(2)-ARs. We have chosen ICI 89,406, a beta(1)-selective AR antagonist, as the lead structure to develop new beta(1)-AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI). (S)-N-[2-[3-(2-Cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]-N'-[4-(2-[(18)F]fluoro-ethoxy)-phenyl]-urea ((S)-[(18)F]F-ICI) was synthesised. Myocardial uptake of radioactivity after intravenous injection of (S)-[(18)F]F-ICI into adult CD(1) mice or Wistar rats was assessed with positron emission tomography (PET) and postmortem dissection. Metabolism was assessed by high-performance liquid chromatography analysis of plasma and urine. The heart was visualised with PET after injection of (S)-[(18)F]F-ICI but neither unlabelled F-ICI nor propranolol (non-selective beta-AR antagonist) injected 15 min after (S)-[(18)F]F-ICI affected myocardial radioactivity. Ex vivo dissection demonstrated that predosing with propranolol or CGP 20712 (beta(1)-selective AR-antagonist) did not affect myocardial radioactivity. Radiometabolites rapidly appeared in plasma and both (S)-[(18)F]F-ICI and radiometabolites accumulated in urine. Myocardial uptake of (S)-[(18)F]F-ICI after intravenous injection was mainly at sites unrelated to beta(1)-ARs. (S)-[(18)F]F-ICI is not a suitable beta(1)-selective-AR radioligand for PET. (c) 2010 Elsevier Inc. All rights reserved.

  8. A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging

    Directory of Open Access Journals (Sweden)

    Jeongsoo Yoo

    2005-01-01

    Full Text Available Dubin-Johnson syndrome (DJS is caused by a deficiency of the human canalicular multispecific organic anion transporter (cMOAT. A new lipophilic copper-64 complex of 1,4,7-tris(carboxymethyl-10-(tetradecyl-1,4,7,10-tetraazadodecane (5 was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64Cu citrate in high radiochemical purity. In vivo uptake and clearance of the complex was determined through biodistribution studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR− rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas activity was accumulated continuously in the liver of TR− rats, it was not excreted into the small intestine. MicroPET studies of normal and TR rats were consistent with biodistribution data and showed dramatically different images. This study strongly suggests that cMOAT is involved in excretion of 64Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR− rats demonstrates that this new 64Cu complex may allow noninvasive diagnosis of DJS in humans.

  9. Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer.

    Science.gov (United States)

    Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

    2018-05-01

    The objective of this study was to investigate whether quantitative imaging features derived from combined 18 F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18 F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (≥Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver-operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18 F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. © 2018 by the Society of Nuclear Medicine and Molecular

  10. Radiosynthesis and autoradiographic evaluation of [{sup 11}C]NAD-299, a radioligand for visualization of the 5-HT{sub 1A} receptor

    Energy Technology Data Exchange (ETDEWEB)

    Sandell, Johan E-mail: Johan.Sandell@psyk.ks.se; Halldin, Christer; Hall, Haakan; Thorberg, Seth-Olov; Werner, Tom; Sohn, Daniel; Sedvall, Goeran; Farde, Lars

    1999-02-01

    The selective 5-HT{sub 1A} receptor antagonist NAD-299 ([R]-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide) was labeled with the positron emitting radionucldie carbon-11. The radioligand was synthesized from NAD-195 ([R]-3-N,N-dicyclobutylamino-8-fluoro-5-trifluoromethylsulfonyloxy-3, 4-dihydro-2H-1-benzopyran) in two radiochemical steps. A palladium-catalyzed reaction of NAD-195 and [{sup 11}C]cyanide was followed by hydrolysis of the carbon-11-labeled nitrile intermediate with basic hydrogen peroxide. The total radiochemical yield, based on [{sup 11}C]CO{sub 2} and corrected for decay, was 20-40%. The specific radioactivity was 24 GBq/{mu}mol (900 Ci/mmol) at end of synthesis, with a radiochemical purity better than 99% and a total synthesis time of 40-45 min. Autoradiographic examination of [{sup 11}C]NAD-299 binding in human brain postmortem demonstrated high binding in hippocampus, raphe nuclei, and neocortex. The binding in the hippocampus was higher than in the neocortex. Within the hippocampus, the densest binding was observed in the CA1 region. [{sup 11}C]NAD-299 binding was inhibited by addition of the 5-HT{sub 1A} receptor ligands WAY-100635, pindolol, ({+-})-8-OH-DPAT, 5-HT, and buspirone, leaving a low background of nonspecific binding. The results indicate that [{sup 11}C]NAD-299 binds specifically to 5-HT{sub 1A} receptors in the human brain in vitro and is a potential radioligand for positron emission tomography (PET) examination of 5-HT{sub 1A} receptors in vivo.

  11. Radiosynthesis and autoradiographic evaluation of [11C]NAD-299, a radioligand for visualization of the 5-HT1A receptor

    International Nuclear Information System (INIS)

    Sandell, Johan; Halldin, Christer; Hall, Haakan; Thorberg, Seth-Olov; Werner, Tom; Sohn, Daniel; Sedvall, Goeran; Farde, Lars

    1999-01-01

    The selective 5-HT 1A receptor antagonist NAD-299 ([R]-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran- 5-carboxamide) was labeled with the positron emitting radionucldie carbon-11. The radioligand was synthesized from NAD-195 ([R]-3-N,N-dicyclobutylamino-8-fluoro-5-trifluoromethylsulfonyloxy-3, 4-dihydro-2H-1-benzopyran) in two radiochemical steps. A palladium-catalyzed reaction of NAD-195 and [ 11 C]cyanide was followed by hydrolysis of the carbon-11-labeled nitrile intermediate with basic hydrogen peroxide. The total radiochemical yield, based on [ 11 C]CO 2 and corrected for decay, was 20-40%. The specific radioactivity was 24 GBq/μmol (900 Ci/mmol) at end of synthesis, with a radiochemical purity better than 99% and a total synthesis time of 40-45 min. Autoradiographic examination of [ 11 C]NAD-299 binding in human brain postmortem demonstrated high binding in hippocampus, raphe nuclei, and neocortex. The binding in the hippocampus was higher than in the neocortex. Within the hippocampus, the densest binding was observed in the CA1 region. [ 11 C]NAD-299 binding was inhibited by addition of the 5-HT 1A receptor ligands WAY-100635, pindolol, (±)-8-OH-DPAT, 5-HT, and buspirone, leaving a low background of nonspecific binding. The results indicate that [ 11 C]NAD-299 binds specifically to 5-HT 1A receptors in the human brain in vitro and is a potential radioligand for positron emission tomography (PET) examination of 5-HT 1A receptors in vivo

  12. [11C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure

    International Nuclear Information System (INIS)

    Croteau, Etienne; Tremblay, Sébastien; Gascon, Suzanne; Dumulon-Perreault, Véronique; Labbé, Sébastien M.; Rousseau, Jacques A.; Cunnane, Stephen C.; Carpentier, André C.; Bénard, François; Lecomte, Roger

    2014-01-01

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic–reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [ 11 C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. Methods: A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [ 14 C]-Acetoacetate, a non-positron (β −) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [ 11 C]-acetoacetate (β +) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(−) (n = 15) and treated Dox(+) (n = 6) rats. The uptake rate (K 1 ) and myocardial clearance rate (k 2 or k mono ) were extracted. Results: [ 14 C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p < 0.05). PET kinetic analysis of [ 11 C]-acetoacetate showed that rate constants K 1 , k 2 and k mono were decreased in Dox(+) (p < 0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p < 0.001). Conclusion: Radioactive acetoacetate ex vivo analysis [ 14 C], and in vivo kinetic [ 11 C] studies provided evidence that [ 11 C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest–stress protocol), [ 11 C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [ 11 C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [ 11 C]-acetoacetate in cardiac pathophysiology

  13. Metabolism and quantification of [18F]DPA-714, a new TSPO positron emission tomography radioligand

    International Nuclear Information System (INIS)

    Peyronneau, Marie-Anne; Saba, Wadad; Goutal, Sebastien; Damont, Annelaure; Dolle, Frederic; Bottlaender, Michel; Valette, Heric; Kassiou, Michael

    2013-01-01

    [ 18 F]DPA-714 [N,N-diethyl-2-(2-(4-(2[ 18 F]-fluoroethoxy)phenyl) 5,7-dimethyl-pyrazolo[1,5a]pyrimidin-3-yl)acetamide] is a new radioligand currently used for imaging the 18-kDa translocator protein in animal models of neuro-inflammation and recently in humans. The biodistribution by positron emission tomography (PET) in baboons and the in vitro and in vivo metabolism of [ 18 F]DPA-714 were investigated in rats, baboons, and humans. Whole-body PET experiments showed a high uptake of radioactivity in the kidneys, heart, liver, and gallbladder. The liver was a major route of elimination of [ 18 F]DPA-714, and urine was a route of excretion for radio-metabolites. In rat and baboon plasma, high-performance liquid chromatography (HPLC) metabolic profiles showed three major radio-metabolites accounting for 85% and 89% of total radioactivity at 120 minutes after injection, respectively. Rat microsomal incubations and analyses by liquid chromatography-mass spectrometry (LC-MS) identified seven metabolites, characterized as O-de-ethyl, hydroxyl, and N-de-ethyl derivatives of nonradioactive DPA-714, two of them having the same retention times than those detected in rat and baboon plasma. The third plasma radio-metabolite was suggested to be a carboxylic acid compound that accounted for 15% of the rat brain radioactivity. O-de-ethylation led to a nonradioactive compound and [ 18 F] fluoroacetic acid. Human CYP3A4 and CYP2D6 were shown to be involved in the oxidation of the radioligand. Finally an easy, rapid, and accurate method-indispensable for PET quantitative clinical studies - for quantifying [ 18 F]DPA-714 by solid-phase extraction was developed. In vivo, an extensive metabolism of [ 18 F]DPA-714 was observed in rats and baboons, identified as [ 18 F]de-ethyl, [ 18 F]hydroxyl, and [ 18 F]carboxylic acid derivatives of [ 18 F]DPA-714. The main route of excretion of the unchanged radioligand in baboons was hepatobiliary while that of radio-metabolites was the urinary

  14. PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

    International Nuclear Information System (INIS)

    Bernards, Nicholas

    2014-01-01

    The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [ 18 F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [ 18 F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [ 18 F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [ 18 F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [ 18 F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [ 18 F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author) [fr

  15. Brain imaging of serotonin 4 receptors in humans with [11C]SB207145-PET

    DEFF Research Database (Denmark)

    Marner, Lisbeth; Gillings, Nic; Madsen, Karine

    2010-01-01

    Pharmacological stimulation of the serotonin 4 (5-HT(4)) receptor has shown promise for treatment of Alzheimer's disease and major depression. A new selective radioligand, [(11)C]SB207145, for positron emission tomography (PET) was used to quantify brain 5-HT(4) receptors in sixteen healthy......(max) was in accordance with post-mortem brain studies (Spearman's r=0.83, p=0.04), and the regional binding potentials, BP(ND), were on average 2.6 in striatum, 0.42 in prefrontal cortex, and 0.91 in hippocampus. We found no effect of sex but a decreased binding with age (p=0.046). A power analysis showed that, given......-HT(4) receptor binding in human brain can be reliably assessed with [(11)C]SB207145, which is encouraging for future PET studies of drug occupancy or patients with neuropsychiatric disorders....

  16. Potential impact of 68Ga-PSMA-11 PET/CT on prostate cancer definitive radiation therapy planning.

    Science.gov (United States)

    Calais, Jérémie; Kishan, Amar U; Cao, Minsong; Fendler, Wolfgang P; Eiber, Matthias; Herrmann, Ken; Ceci, Francesco; Reiter, Robert E; Matthew, Rettig B; Hegde, John V; Shaverdian, Narek; King, Christopher R; Steinberg, Michael L; Czernin, Johannes; Nickols, Nicholas G

    2018-04-13

    Background: Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) detects PCa metastasis with superior accuracy with potential impact definitive radiation therapy (RT) planning for non-metastatic PCa. Objectives: i) To determine how often definitive PCa RT planning based on standard target volumes cover 68 Ga-PSMA-11 PET/CT defined disease, and ii) To assess the potential impact of 68 Ga-PSMA-11 PET/CT on definitive PCa RT planning. Patients and Methods: This is a post-hoc analysis of an intention to treat population of 73 patients with localized PCa without prior local therapy who underwent 68 Ga-PSMA PET/CT for initial staging as part of an Investigational New Drug trial. 11/73 were intermediate-risk (15%), 33/73 were high-risk (45%), 22/73 were very high risk (30%), and 7/73 were N1 (9.5%). Clinical target volumes (CTVs) that included the prostate, seminal vesicles, and pelvic lymph nodes (LNs) using Radiation Therapy Oncology Group (RTOG) consensus guidelines were contoured on the CT portion of the PET/CT by a radiation oncologist blinded to the PET findings. 68 Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. PSMA-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had PSMA-positive primary prostate lesion(s). 25/73 (34%) and 7/73 (9.5%) had PSMA-positive pelvic nodal and distant metastases, respectively. The sites of nodal metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper-diaphragm (4%), and presacral (1.5%). The median size of the nodal lesions was 6 mm (range 4-24 mm). RT planning based on the CTVs covered 69/73 (94.5%) of primary disease and 20/25 (80%) of

  17. Quantitative assessment of the physical potential of proton beam range verification with PET/CT

    NARCIS (Netherlands)

    Knopf, A; Parodi, K.; Paganetti, Harald; Lo Cascio, E; Bonab, A; Bortfeld, Thomas

    2008-01-01

    A recent clinical pilot study demonstrated the feasibility of offline PET/CT range verification for proton therapy treatments. In vivo PET measurements are challenged by blood perfusion, variations of tissue compositions, patient motion and image co-registration uncertainties. Besides these

  18. Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

    DEFF Research Database (Denmark)

    Persson, Morten; Nedergaard, Mette K; Brandt-Larsen, Malene

    2016-01-01

    an orthotopic xenograft model of glioblastoma. Tumor growth was monitored using bioluminescence imaging. Five to six weeks after inoculation, all mice were scanned with small-animal PET/CT using two new uPAR PET ligands ((64)Cu-NOTA-AE105 and (68)Ga-NOTA-AE105) and, for comparison, O-(2-(18)F...

  19. Preliminary studies with (/sup 18/F)haloperidol: a radioligand for in vivo studies of the dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Tewson, T J; Raichle, M E; Welch, M J [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

    1980-06-16

    The authors report a synthesis of (/sup 18/F)haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system.

  20. Preliminary studies with [18F]haloperidol: a radioligand for in vivo studies of the dopamine receptors

    International Nuclear Information System (INIS)

    Tewson, T.J.; Raichle, M.E.; Welch, M.J.

    1980-01-01

    The authors report a synthesis of [ 18 F]haloperidol of sufficiently high specific activity to permit the mapping of dopamine receptors in vivo in man using PET. The preliminary work with this radioligand in vivo in monkeys clearly suggests that haloperidol enters brain from blood by means of carrier-mediated, facilitated diffusion rather than simple diffusion. This rather surprising observation not only assumes special importance in the interpretation of in vivo pharmacokinetic data on dopamine receptors in man or animals but may also be important in considerations of the possible mode of action of this drug on the central nervous system. (Auth.)

  1. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Gottingen minipig

    DEFF Research Database (Denmark)

    Kornum, B.R.; Lind, N.M.; Gillings, N.

    2009-01-01

    This study investigates 5-hydroxytryptamine 4 (5-HT(4)) receptor binding in the minipig brain with positron emission tomography (PET), tissue homogenate-binding assays, and autoradiography in vitro. The cerebral uptake and binding of the novel 5-HT(4) receptor radioligand [(11)C]SB207145 in vivo...... was modelled and the outcome compared with postmortem receptor binding. Different models for quantification of [(11)C]SB207145 binding were evaluated: One-tissue and two-tissue compartment kinetic modelling, Logan arterial input, and three different reference tissue models. We report that the pig...... model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...

  2. A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

    International Nuclear Information System (INIS)

    Finnema, Sjoerd J.; Seneca, Nicholas; Farde, Lars; Shchukin, Evgeny; Sovago, Judit; Gulyas, Balazs; Wikstroem, Hakan V.; Innis, Robert B.; Neumeyer, John L.; Halldin, Christer

    2005-01-01

    This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D 2 -like receptor agonist (R)-2- 11 CH 3 O-N-n-propylnorapomorphine ([ 11 C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D 2 receptor (D 2 R). MNPA is a selective D 2 -like receptor agonist with a high affinity (K i =0.17 nM). [ 11 C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [ 11 C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D 2 R, with a maximum striatum-to-cerebellum ratio of 2.23±0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37±0.06 at 72 min. The pretreatment study demonstrated high specific binding to D 2 R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [ 11 C]MNPA has potential as an agonist radioligand for the D 2 -like receptor and has potential for examination of the high-affinity state of the D 2 R in human subjects and patients with neuropsychiatric disorders

  3. Application of cross-species PET imaging to assess neurotransmitter release in brain.

    Science.gov (United States)

    Finnema, Sjoerd J; Scheinin, Mika; Shahid, Mohammed; Lehto, Jussi; Borroni, Edilio; Bang-Andersen, Benny; Sallinen, Jukka; Wong, Erik; Farde, Lars; Halldin, Christer; Grimwood, Sarah

    2015-11-01

    This review attempts to summarize the current status in relation to the use of positron emission tomography (PET) imaging in the assessment of synaptic concentrations of endogenous mediators in the living brain. Although PET radioligands are now available for more than 40 CNS targets, at the initiation of the Innovative Medicines Initiative (IMI) "Novel Methods leading to New Medications in Depression and Schizophrenia" (NEWMEDS) in 2009, PET radioligands sensitive to an endogenous neurotransmitter were only validated for dopamine. NEWMEDS work-package 5, "Cross-species and neurochemical imaging (PET) methods for drug discovery", commenced with a focus on developing methods enabling assessment of changes in extracellular concentrations of serotonin and noradrenaline in the brain. Sharing the workload across institutions, we utilized in vitro techniques with cells and tissues, in vivo receptor binding and microdialysis techniques in rodents, and in vivo PET imaging in non-human primates and humans. Here, we discuss these efforts and review other recently published reports on the use of radioligands to assess changes in endogenous levels of dopamine, serotonin, noradrenaline, γ-aminobutyric acid, glutamate, acetylcholine, and opioid peptides. The emphasis is on assessment of the availability of appropriate translational tools (PET radioligands, pharmacological challenge agents) and on studies in non-human primates and human subjects, as well as current challenges and future directions. PET imaging directed at investigating changes in endogenous neurochemicals, including the work done in NEWMEDS, have highlighted an opportunity to further extend the capability and application of this technology in drug development.

  4. [18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey

    International Nuclear Information System (INIS)

    Hostetler, Eric D.; Sanabria-Bohórquez, Sandra; Fan Hong; Zeng, Zhizhen; Gammage, Linda; Miller, Patricia; O'Malley, Stacey; Connolly, Brett; Mulhearn, James; Harrison, Scott T.; Wolkenberg, Scott E.; Barrow, James C.; Williams, David L.; Hargreaves, Richard J.; Sur, Cyrille; Cook, Jacquelynn J.

    2011-01-01

    Introduction: An 18 F-labeled positron emission tomography (PET) tracer for amyloid plaque is desirable for early diagnosis of Alzheimer's disease, particularly to enable preventative treatment once effective therapeutics are available. Similarly, such a tracer would be useful as a biomarker for enrollment of patients in clinical trials for evaluation of antiamyloid therapeutics. Furthermore, changes in the level of plaque burden as quantified by an amyloid plaque PET tracer may provide valuable insights into the effectiveness of amyloid-targeted therapeutics. This work describes our approach to evaluate and select a candidate PET tracer for in vivo quantification of human amyloid plaque. Methods: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood–brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with 18 F and evaluated in vivo. Baseline PET scans in rhesus monkey were conducted to evaluate the regional distribution and kinetics of each tracer using tracer kinetic modeling methods. High binding potential in cerebral white matter and cortical grey matter was considered an unfavorable feature of the candidate tracers. Results: [ 18 F]MK-3328 showed the most favorable combination of low in vivo binding potential in white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log D=2.91) and high affinity for human amyloid plaques (IC 50 =10.5±1.3 nM). Conclusions: [ 18 F]MK-3328 was identified as a promising PET tracer for in vivo quantification of amyloid plaques, and further evaluation in humans is warranted.

  5. PET imaging of adenosine A2A receptors

    NARCIS (Netherlands)

    Zhou, Xiaoyun

    2017-01-01

    This thesis describes the development and evaluation of [11C]preladenant as a novel radioligand for in vivo imaging of adenosine A2A receptors in the brain with positron-emission tomography (PET). The 11C-labeled drug [11C]preladenant was produced with high radiochemical yield and specific activity.

  6. PET Centre and Centre for Functionally Integrative Neuroscience, Aarhus University

    DEFF Research Database (Denmark)

    Cumming, Paul; Pedersen, Mads Damgaard; Minuzzi, Luciano

    2006-01-01

    The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 bin...

  7. Characterisation of [11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

    Energy Technology Data Exchange (ETDEWEB)

    Riss P. J.; Fowler J.; Riss, P.J.; Hooker, J.M.; Shea, C.; Xu, Y.; Carter, P.; Warner, D.; Ferrari V.; Kim, S.W.; Aigbirhio, F.I.; Fowler, J.S.; Roesch, F.

    2011-10-25

    N-(4-fluorobut-2-yn-1-yl)-2{beta}-carbomethoxy-3{beta}-(4{prime}-tolyl)nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [{sup 11}C]PR04.MZ ([{sup 11}C]-1) has been developed using GMP compliant equipment. An adult female Papioanubis baboon was studied using a test-retest protocol with [{sup 11}C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (fP), plasma input functions and metabolic degradation of the radiotracer [{sup 11}C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (VT) and non-displaceable binding potentials (BPND) for various brain regions and the blood were obtained from kinetic modelling. [{sup 11}C]-1 shows promising results as aselective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

  8. Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results

    International Nuclear Information System (INIS)

    Dietlein, M.; Weber, K.; Moka, D.; Theissen, P.; Schicha, H.

    2000-01-01

    Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost

  9. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    Science.gov (United States)

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

    2014-05-01

    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; pholes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Synthesis of Sulochrin-125I and Its Binding Affinity as α-Glucosidase Inhibitor using Radioligand Binding Assay (RBA Method

    Directory of Open Access Journals (Sweden)

    W. Lestari

    2014-04-01

    Full Text Available Most of diabetics patients have type 2 diabetes mellitus or non insulin dependent diabetes mellitus. Treatment type 2 diabetes mellitus can be done by inhibiting α-glucosidase enzyme which converts carbohydrates into glucose. Sulochrin is one of the potential compounds which can inhibit the function of α-glucosidase enzyme. This study was carried out to obtain data of sulochrin binding with α-glucosidase enzyme as α-glucosidase inhibitor using Radioligand Binding Assay (RBA method. Primary reagent required in RBA method is labeled radioactive ligand (radioligand. In this study, the radioligand was sulochrin-125I and prior to sulochrin-125I synthesis, the sulochrin-I was synthesized. Sulochrin-I and sulochrin-125I were synthesized and their bindings were studied using Radioligand Binding Assay method. Sulochrin-I was synthesized with molecular formula C17H15O7I and molecular weight 457.9940. Sulochrin-125I was synthesized from sulochrin-I by isotope exchange method. From the RBA method, dissociation constant (Kd and maximum binding (Bmax were obtained 26.316 nM and Bmax 9.302 nM respectively. This low Kd indicated that sulochrin was can bind to α-glucosidase

  11. Tiny Turtles Purchased at Pet Stores are a Potential High Risk for Salmonella Human Infection in the Valencian Region, Eastern Spain.

    Science.gov (United States)

    Marin, Clara; Vega, Santiago; Marco-Jiménez, Francisco

    2016-07-01

    Turtles may be considered unsafe pets, particularly in households with children. This study aimed to assess Salmonella carriage by turtles in pet stores and in private ownership to inform the public of the potential health risk, enabling informed choices around pet selection. During the period between September and October 2013, 24 pet stores and 96 private owners were sampled in the Valencian Region (Eastern Spain). Salmonella identification procedure was based on ISO 6579: 2002 recommendations (Annex D). Salmonella strains were serotyped in accordance with Kauffman-White-Le-Minor technique. The rate of isolation of Salmonella was very high from pet store samples (75.0% ± 8.8%) and moderate for private owners (29.0% ± 4.6%). Serotyping revealed 18 different serotypes among two Salmonella enterica subspecies: S. enterica subsp. enterica and S. enterica subsp. diarizonae. Most frequently isolated serotypes were Salmonella Typhimurium (39.5%, 17/43) and Salmonella Pomona (9.3%, 4/43). Serotypes identified have previously been reported in turtles, and child Salmonella infections associate with pet turtle exposure. The present study clearly demonstrates that turtles in pet stores, as well as in private owners, could be a direct or indirect source of a high risk of human Salmonella infections. In addition, pet stores should advise their customers of the potential risks associated with reptile ownership.

  12. Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging

    Directory of Open Access Journals (Sweden)

    Genchel Tove

    2007-07-01

    Full Text Available Abstract Background The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171. Methods [1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethyl-2-phenylpiperidin-3-amine (I and (2S,3S-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl-4H-1,2,4-triazol-4-ylphenylethylpiperidin-3-amine (II was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171. Results All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II had no specific binding in striatum. Ligand (I had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171. Conclusion The propyl-analogue (II cannot be used for detecting changes in NK1-ligand levels, while further studies should be

  13. Serotonin transporter occupancy by escitalopram and citalopram in the non-human primate brain: a [(11)C]MADAM PET study.

    Science.gov (United States)

    Finnema, Sjoerd J; Halldin, Christer; Bang-Andersen, Benny; Bundgaard, Christoffer; Farde, Lars

    2015-11-01

    A number of serotonin receptor positron emission tomography (PET) radioligands have been shown to be sensitive to changes in extracellular serotonin concentration, in a generalization of the well-known dopamine competition model. High doses of selective serotonin reuptake inhibitors (SSRIs) decrease serotonin receptor availability in monkey brain, consistent with increased serotonin concentrations. However, two recent studies on healthy human subjects, using a single, lower and clinically relevant SSRI dose, showed increased cortical serotonin receptor radioligand binding, suggesting potential decreases in serotonin concentration in projection regions when initiating treatment. The cross-species differential SSRI effect may be partly explained by serotonin transporter (SERT) occupancy in monkey brain being higher than is clinically relevant. We here determine SERT occupancy after single doses of escitalopram or citalopram by conducting PET measurements with [(11)C]MADAM in monkeys. Relationships between dose, plasma concentration and SERT occupancy were estimated by one-site binding analyses. Binding affinity was expressed as dose (ID50) or plasma concentration (K i) where 50 % SERT occupancy was achieved. Estimated ID50 and K i values were 0.020 mg/kg and 9.6 nmol/L for escitalopram and 0.059 mg/kg and 9.7 nmol/L for citalopram, respectively. Obtained K i values are comparable to values reported in humans. Escitalopram or citalopram doses nearly saturated SERT in previous monkey studies which examined serotonin sensitivity of receptor radioligands. PET-measured cross-species differential effects of SSRI on cortical serotonin concentration may thus be related to SSRI dose. Future monkey studies using SSRI doses inducing clinically relevant SERT occupancy may further illuminate the delayed onset of SSRI therapeutic effects.

  14. Development of a PET tracer for imaging EGFR tyrosine kinase: evaluation of the suitability of PKI166

    International Nuclear Information System (INIS)

    Kernchen, R.; Brust, P.; Krause, M.; Baumann, M.

    2002-01-01

    The suitability of PKI166 for the development of a PET tracer for imaging EGFR tyrosine kinase was investigated. Binding studies using EGFR positive tumour tissue and tritiated PKI166 as the radioligand indicated a low binding affinity of PKI166 to the target tissue. PKI166 is therefore not recommended for PET tracer development. (orig.)

  15. Cerebral lesions and event-related potential P300 using positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Sakai, Yasujiro; Okamoto, Kazuma; Tanaka, Makoto; Kondoh, Susumu; Hirai, Shunsaku

    1993-01-01

    To determine what lesions are involved in prolonging event-related potential P300 latency, regional cerebral blood flow (rCBF) and metabolism were investigated by positron emission tomography (PET) in a total of 40 patients with neurologic diseases (12 with chronic cerebrovascular disorder, 9 with spino-cerebellar degeneration, 4 with Alzheimer's type dementia, 4 with amyotrophic lateral sclerosis, and 11 with miscellaneous diseases). There was inverse correlation between rCBF and P300 latency in terms of any of the whole, left, and right hemispheres: P300 latency was associated with decreased rCBF. This was more noticeable in the cerebral cortex than white matter and in the right than left hemisphere, although there was no significant difference between them. In none of the regions, however, was there significant correlation between cerebral oxygen consumption and P300 latency. When the right and left frontal, temporal, parietal and occipital cortexes, thalamus, putamen, and caudatum were examined as regions of interest, there was significantly inverse correlation between rCBF and P300 latency in all regions except for the occipital cortex. This was more noticeable on the right than the left side, although no significant difference was observed. Cerebral oxygen consumption in these lesions did not correlate with P300 latency. In the study on bilateral rCBF difference, decreased rCBF confined to the right parietal lobe, bilateral thalamus and bilateral temporal lobes was found to be associated with a significantly prolonged P300 latency. Thus, rCBF in these regions seemed to be particularly responsible for P300 latency. (N.K.)

  16. Cerebral lesions and event-related potential P300 using positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Yasujiro; Okamoto, Kazuma; Tanaka, Makoto; Kondoh, Susumu; Hirai, Shunsaku (Gunma Univ., Maebashi (Japan). School of Medicine)

    1993-06-01

    To determine what lesions are involved in prolonging event-related potential P300 latency, regional cerebral blood flow (rCBF) and metabolism were investigated by positron emission tomography (PET) in a total of 40 patients with neurologic diseases (12 with chronic cerebrovascular disorder, 9 with spino-cerebellar degeneration, 4 with Alzheimer's type dementia, 4 with amyotrophic lateral sclerosis, and 11 with miscellaneous diseases). There was inverse correlation between rCBF and P300 latency in terms of any of the whole, left, and right hemispheres: P300 latency was associated with decreased rCBF. This was more noticeable in the cerebral cortex than white matter and in the right than left hemisphere, although there was no significant difference between them. In none of the regions, however, was there significant correlation between cerebral oxygen consumption and P300 latency. When the right and left frontal, temporal, parietal and occipital cortexes, thalamus, putamen, and caudatum were examined as regions of interest, there was significantly inverse correlation between rCBF and P300 latency in all regions except for the occipital cortex. This was more noticeable on the right than the left side, although no significant difference was observed. Cerebral oxygen consumption in these lesions did not correlate with P300 latency. In the study on bilateral rCBF difference, decreased rCBF confined to the right parietal lobe, bilateral thalamus and bilateral temporal lobes was found to be associated with a significantly prolonged P300 latency. Thus, rCBF in these regions seemed to be particularly responsible for P300 latency. (N.K.).

  17. 64Cu-PSMA-617 PET/CT Imaging of Prostate Adenocarcinoma: First In-Human Studies.

    Science.gov (United States)

    Grubmüller, Bernhard; Baum, Richard P; Capasso, Enza; Singh, Aviral; Ahmadi, Yasaman; Knoll, Peter; Floth, Andreas; Righi, Sergio; Zandieh, Shahin; Meleddu, Carlo; Shariat, Shahrokh F; Klingler, Hans Christoph; Mirzaei, Siroos

    2016-10-07

    The prostate-specific membrane antigen (PSMA) is a cell surface protein, which is overexpressed in nearly all cases of prostate cancer (PCa). PET imaging with 68 Ga-PSMA-HBED-CC has recently found widespread application in the diagnosis of recurrent PCa. In this study, the diagnostic potential of 64 Cu-labeled PSMA ligand (PSMA-617) PET in patients with PCa has been investigated. The study was conducted simultaneously at two nuclear medicine centers, Austria (Vienna, Center 1) and Germany (Bad Berka, Center 2). The patients (n = 29) included in this study were referred for PET (Center 1, 21 patients) or PET/CT (Center 2, 8 patients) imaging with either a high suspicion of recurrent disease or for possible surgical or PSMA radioligand therapy planning. PET images of the whole body were performed at 1 hour p.i. and additional images of the pelvis at 2 hours p.i. In 23 of 29 patients, at least one focus of pathological tracer uptake suspicious for primary disease in the prostate lobe or recurrent disease was detected. Among healthy organs, the salivary glands, kidneys, and liver showed the highest radiotracer uptake. Lesions suspicious for PCa were detected with excellent contrast as early as 1 hour p.i. with high detection rates even at low prostate-specific antigen (PSA) levels. The preliminary results of this study demonstrate the high potential of 64 Cu-PSMA ligand PET/CT imaging in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. The acquired PET images showed an excellent resolution of the detected lesions with very high lesion-to- background contrast. Furthermore, the long half-life of 64 Cu allows distribution of the tracer to clinical PET centers that lack radiochemistry facilities for the preparation of 68 Ga-PSMA ligand (satellite concept).

  18. Radioiodinated SB 207710 as a radioligand in vivo: imaging of brain 5-HT{sub 4} receptors with SPET

    Energy Technology Data Exchange (ETDEWEB)

    Pike, Victor W. [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); PET Radiopharmaceutical Sciences Section, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3 C346A, 10 Center Drive, MD 20892-1003, Bethesda (United States); Halldin, Christer; Nobuhara, Kenji; Swahn, Carl-Gunnar; Karlsson, Per; Olsson, Hans; Larsson, Stig; Schnell, Per-Olof; Farde, Lars [Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska Hospital, 17176, Stockholm (Sweden); Hiltunen, Julka [MAP Medical Technologies, Oy, Tikkakoski (Finland); Mulligan, Rachel S. [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Institute of Psychiatry, SE 8AF, De Crespigny Park, Denmark Hill, London (United Kingdom); Centre for PET, Austin and Repatriation Medical Centre, Studley Road, Melbourne VIC 3084 (Australia); Hume, Susan P.; Hirani, Ella [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Imaging Research Solutions Ltd., Cyclotron Building, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Whalley, Jaqueline [MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, Ducane Road, W12 0NN, London (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, SE 8AF, De Crespigny Park, Denmark Hill, London (United Kingdom); Institute of Nuclear Medicine, Royal Free and University College, Medical School, Mortimer Street, W1N 8AA, London (United Kingdom); Ell, Peter J. [Institute of Nuclear Medicine, Royal Free and University College, Medical School, Mortimer Street, W1N 8AA, London (United Kingdom)

    2003-11-01

    Single-photon emission tomography (SPET) and positron emission tomography (PET), when coupled to suitable radioligands, are uniquely powerful for investigating the status of neurotransmitter receptors in vivo. The serotonin subtype-4 (5-HT{sub 4}) receptor has discrete and very similar distributions in rodent and primate brain. This receptor population may play a role in normal cognition and memory and is perhaps perturbed in some neuropsychiatric disorders. SB 207710 [(1-butyl-4-piperidinylmethyl)-8-amino-7-iodo-1,4-benzodioxan-5-carboxylate] is a selective high-affinity antagonist at 5-HT{sub 4} receptors. We explored radioiodinated SB 207710 as a possible radioligand for imaging 5-HT{sub 4} receptors in vivo. Rats were injected intravenously with iodine-125 labelled SB 207710, euthanised at known times and dissected to establish radioactivity content in brain tissues. Radioactivity entered brain but cleared rapidly and to a high extent from blood and plasma. Between 45 and 75 min after injection, the ratios of radioactivity concentration in each of 12 selected brain tissues to that in receptor-poor cerebellum correlated with previous measures of 5-HT{sub 4} receptor density distribution in vitro. The highest ratio was about 3.4 in striatum. SB 207710 was labelled with iodine-123 by an iododestannylation procedure. A cynomolgus monkey was injected intravenously with [{sup 123}I]SB 207710 and examined by SPET. Maximal whole brain uptake of radioactivity was 2.3% of the injected dose at 18 min after radioligand injection. Brain images acquired between 9 and 90 min showed high radioactivity uptake in 5-HT{sub 4} receptor-rich regions, such as striatum, and low uptake in receptor-poor cerebellum. At 169 min the ratio of radioactivity concentration in striatum to that in cerebellum was 4.0. In a second SPET experiment, the cynomolgus monkey was pretreated with a selective 5-HT{sub 4} receptor antagonist, SB 204070, at 20 min before [{sup 123}I]SB 207710 injection

  19. Evaluation of the novel 5-HT4 receptor PET ligand [11C]SB207145 in the Göttingen minipig

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Lind, Nanna M; Gillings, Nic

    2009-01-01

    This study investigates 5-hydroxytryptamine 4 (5-HT(4)) receptor binding in the minipig brain with positron emission tomography (PET), tissue homogenate-binding assays, and autoradiography in vitro. The cerebral uptake and binding of the novel 5-HT(4) receptor radioligand [(11)C]SB207145 in vivo...... was modelled and the outcome compared with postmortem receptor binding. Different models for quantification of [(11)C]SB207145 binding were evaluated: One-tissue and two-tissue compartment kinetic modelling, Logan arterial input, and three different reference tissue models. We report that the pig...... model provides stable and precise estimates of the binding potential in all regions. The binding potentials calculated for striatum, midbrain, and cortex from the PET data were highly correlated with 5-HT(4) receptor concentrations determined in brain homogenates from the same regions, except...

  20. Scalene muscle uptake: a potential pitfall in head and neck PET/CT

    International Nuclear Information System (INIS)

    Jacene, Heather A.; Goudarzi, Behnaz; Wahl, Richard L.

    2008-01-01

    To describe increased 2-deoxy-2-[ 18 F] fluoro-D-glucose (FDG) uptake in the scalene muscles in a large population of patients referred for evaluation with FDG positron emission tomography/computed tomography (PET/CT) imaging. The study met criteria for institutional review board exemption. FDG PET/CT images from 410 patients (179 males; mean age 56.8 years, range 6-88) were retrospectively reviewed for the presence or absence of FDG uptake in the neck that corresponded to the scalene muscles on the concurrent CT scan. Medical records were reviewed and data including age, sex, smoking history, reason for referral, and history of obstructive airways disease, thoracotomy, and thoracic radiation were recorded and evaluated. One hundred and forty-seven of the 410 scans (36%) demonstrated increased FDG uptake on PET that corresponded to the scalene muscles on the CT scan. The uptake was most often bilateral, symmetrical, and linear (n = 117). Other patterns of scalene muscle uptake included unilateral and linear uptake (n = 27) and unilateral and focal uptake (n = 3). Scalene muscle uptake was more common in patients referred for evaluation of lung carcinomas compared to other types of tumors (52% vs. 32%, p = 0.05). Linear FDG uptake in scalene muscles is a commonly seen pattern on PET/CT. This finding should be recognized as a distinct entity and not misinterpreted on transverse images as metastatic disease. (orig.)

  1. Evaluation of potential PET imaging probes for the orexin 2 receptors

    International Nuclear Information System (INIS)

    Wang, Changning; Wilson, Colin M.; Moseley, Christian K.; Carlin, Stephen M.; Hsu, Shirley; Arabasz, Grae; Schroeder, Frederick A.; Sander, Christin Y.; Hooker, Jacob M.

    2013-01-01

    A wide range of central nervous system (CNS) disorders, particularly those related to sleep, are associated with the abnormal function of orexin (OX) receptors. Several orexin receptor antagonists have been reported in recent years, but currently there are no imaging tools to probe the density and function of orexin receptors in vivo. To date there are no published data on the pharmacokinetics (PK) and accumulation of some lead orexin receptor antagonists. Evaluation of CNS pharmacokinetics in the pursuit of positron emission tomography (PET) radiotracer development could be used to elucidate the association of orexin receptors with diseases and to facilitate the drug discovery and development. To this end, we designed and evaluated carbon-11 labeled compounds based on diazepane orexin receptor antagonists previously described. One of the synthesized compounds, [ 11 C]CW4, showed high brain uptake in rats and further evaluated in non-human primate (NHP) using PET-MR imaging. PET scans performed in a baboon showed appropriate early brain uptake for consideration as a radiotracer. However, [ 11 C]CW4 exhibited fast kinetics and high nonspecific binding, as determined after co-administration of [ 11 C]CW4 and unlabeled CW4. These properties indicate that [ 11 C]CW4 has excellent brain penetrance and could be used as a lead compound for developing new CNS-penetrant PET imaging probes of orexin receptors

  2. Revolutionary impact of PET and PET-CT on the day-to-day practice of medicine and its great potential for improving future health care

    International Nuclear Information System (INIS)

    Basu, S.; Alavi, A.

    2009-01-01

    In this communication, we present an overview of the impact and advantages of PET and PET-CT fusion imaging in the practice of medicine. We also discuss the evolution of this promising molecular imaging technique since its inception and the future prospects of the combined structure-function approach. Superior contrast resolution, accurate quantification and above all optimal image quality aid in improved diagnosis of many serious disorders including cancer. We speculate that this powerful imaging approach will almost completely replace most other conventional methods in the future. Currently, 18[F]-fluorodeoxyglucose (FDG) is the main radiopharmaceutical employed for PET studies around the globe. With the availability of high quality PET images on a routine basis in most centres around the world and the likelihood that several other useful PET tracers will be approved in the near future for routine clinical applications, this technique will likely become essential in almost any medical disorder. (authors)

  3. High throughput static and dynamic small animal imaging using clinical PET/CT: potential preclinical applications

    International Nuclear Information System (INIS)

    Aide, Nicolas; Desmonts, Cedric; Agostini, Denis; Bardet, Stephane; Bouvard, Gerard; Beauregard, Jean-Mathieu; Roselt, Peter; Neels, Oliver; Beyer, Thomas; Kinross, Kathryn; Hicks, Rodney J.

    2010-01-01

    The objective of the study was to evaluate state-of-the-art clinical PET/CT technology in performing static and dynamic imaging of several mice simultaneously. A mouse-sized phantom was imaged mimicking simultaneous imaging of three mice with computation of recovery coefficients (RCs) and spillover ratios (SORs). Fifteen mice harbouring abdominal or subcutaneous tumours were imaged on clinical PET/CT with point spread function (PSF) reconstruction after injection of [18F]fluorodeoxyglucose or [18F]fluorothymidine. Three of these mice were imaged alone and simultaneously at radial positions -5, 0 and 5 cm. The remaining 12 tumour-bearing mice were imaged in groups of 3 to establish the quantitative accuracy of PET data using ex vivo gamma counting as the reference. Finally, a dynamic scan was performed in three mice simultaneously after the injection of 68 Ga-ethylenediaminetetraacetic acid (EDTA). For typical lesion sizes of 7-8 mm phantom experiments indicated RCs of 0.42 and 0.76 for ordered subsets expectation maximization (OSEM) and PSF reconstruction, respectively. For PSF reconstruction, SOR air and SOR water were 5.3 and 7.5%, respectively. A strong correlation (r 2 = 0.97, p 2 = 0.98; slope = 0.89, p 2 = 0.96; slope = 0.62, p 68 Ga-EDTA dynamic acquisition. New generation clinical PET/CT can be used for simultaneous imaging of multiple small animals in experiments requiring high throughput and where a dedicated small animal PET system is not available. (orig.)

  4. Preclinical evaluation and test-retest studies of [{sup 18}F]PSS232, a novel radioligand for targeting metabotropic glutamate receptor 5 (mGlu{sub 5})

    Energy Technology Data Exchange (ETDEWEB)

    Milicevic Sephton, Selena; Mueller Herde, Adrienne; Keller, Claudia; Ruedisuehli, Sonja; Schibli, Roger; Kraemer, Stefanie D.; Ametamey, Simon M. [Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Zurich (Switzerland); Mu, Linjing [University Hospital Zuerich, Department of Nuclear Medicine, Zuerich (Switzerland); Auberson, Yves [Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel (Switzerland)

    2015-01-15

    A novel, {sup 18}F-labelled metabotropic glutamate receptor subtype 5 (mGlu{sub 5}) derivative of [{sup 11}C]ABP688 ([{sup 11}C]1), [{sup 18}F]PSS232 ([{sup 18}F]5), was evaluated in vitro and in vivo for its potential as a PET agent and was used in test-retest reliability studies The radiosynthesis of [{sup 18}F]5 was accomplished via a one-step reaction using a mesylate precursor. In vitro stability was determined in PBS and plasma, and with liver microsomal enzymes. Metabolite studies were performed using rat brain extracts, blood and urine. In vitro autoradiography was performed on horizontal slices of rat brain using 1 and 8, antagonists for mGlu{sub 5} and mGlu{sub 1}, respectively. Small-animal PET, biodistribution, and test-retest studies were performed in Wistar rats. In vivo, dose-dependent displacement studies were performed using 6 and blocking studies with 7. [{sup 18}F]5 was obtained in decay-corrected maximal radiochemical yield of 37 % with a specific activity of 80 - 400 GBq/μmol. Treatment with rat and human microsomal enzymes in vitro for 60 min resulted in 20 % and 4 % of hydrophilic radiometabolites, respectively. No hydrophilic decomposition products or radiometabolites were found in PBS or plasma. In vitro autoradiography on rat brain slices showed a heterogeneous distribution consistent with the known distribution of mGlu{sub 5} with high binding to hippocampal and cortical regions, and negligible radioactivity in the cerebellum. Similar distribution of radioactivity was found in PET images. Under displacement conditions with 6, reduced [{sup 18}F]5 binding was found in all brain regions except the cerebellum. 7 reduced binding in the striatum by 84 % on average. Test-retest studies were reproducible with a variability ranging from 6.8 % to 8.2 %. An extended single-dose toxicity study in Wistar rats showed no compound-related adverse effects. The new mGlu{sub 5} radiotracer, [{sup 18}F]5, showed specific and selective in vitro and in vivo

  5. Radiosynthesis and in vivo evaluation of [{sup 11}C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A

    Energy Technology Data Exchange (ETDEWEB)

    Plisson, Christophe, E-mail: Christophe.2.plisson@gsk.com [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Salinas, Cristian [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Weinzimmer, David; Labaree, David; Lin, Shu-Fei; Ding, Yu-Shin [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Jakobsen, Steen [Aarhus PET Centre, Aarhus Sygehus, Norrebrogade 44, DK-8000 Aarhus C (Denmark); Smith, Paul W. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom); Eiji, Kawanishi [Medicinal Chemistry Research Laboratories II, Research Division, Mitsubishi Tanabe Pharma Corporation, Saitama 335-8505 (Japan); Carson, Richard E. [Yale University PET Center, Yale University School of Medicine, PO Box 208048 New Haven, CT (United States); Gunn, Roger N.; Rabiner, Eugenii A. [GlaxoSmithKline, Clinical Imaging Centre Hammersmith Hospital, London, W12 0NN (United Kingdom)

    2011-08-15

    Introduction: The aim of this study was to evaluate a newly reported positron emission tomography (PET) radioligand [{sup 11}C]MP-10, a potent and selective inhibitor of the central phosphodiesterase 10A enzyme (PDE10A) in vivo, using PET. Methods: A procedure was developed for labeling MP-10 with carbon-11. [{sup 11}C]MP-10 was evaluated in vivo both in the pig and baboon brain. Results: Alkylation of the corresponding desmethyl compound with [{sup 11}C]methyl iodide produced [{sup 11}C]MP-10 with good radiochemical yield and specific activity. PET studies in the pig showed that [{sup 11}C]MP-10 rapidly entered the brain reaching peak tissue concentration at 1-2 min postadministration, followed by washout from the tissue. Administration of a selective PDE10A inhibitor reduced the binding in all brain regions to the levels of the cerebellum, demonstrating the saturability and selectivity of [{sup 11}C]MP-10 binding. In the nonhuman primate, the brain tissue kinetics of [{sup 11}C]MP-10 were slower, reaching peak tissue concentrations at 30-60 min postadministration. In both species, the observed rank order of regional brain signal was striatum>diencephalon>cortical regions=cerebellum, consistent with the known distribution and concentration of PDE10A. [{sup 11}C]MP-10 brain kinetics were well described by a two-tissue compartment model, and estimates of total volume of distribution (V{sub T}) were obtained. Blocking studies with unlabeled MP-10 revealed the suitability of the cerebellum as a reference tissue and enabled the estimation of regional binding potential (BP{sub ND}) as the outcome measure of specific binding. Quantification of [{sup 11}C]MP-10 binding using the simplified reference tissue model with cerebellar input function produced BP{sub ND} estimates consistent with those obtained by the two-tissue compartment model. Conclusion: We demonstrated that [{sup 11}C]MP-10 possesses good characteristics for the in vivo quantification of the PDE10A in the

  6. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18f]fluorobenzoate

    International Nuclear Information System (INIS)

    Jonson, Stephanie D.; Welch, Michael J.

    1999-01-01

    Cholesteryl-p-[ 18 F]fluorobenzoate ([ 18 F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [ 18 F]CFB. The synthesis of [ 18 F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [ 18 F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [ 18 F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [ 18 F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [ 18 F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [ 18 F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [ 18 F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders

  7. Preclinical Evaluation of 18F-RO6958948, 11C-RO6931643, and 11C-RO6924963 as Novel PET Radiotracers for Imaging Tau Aggregates in Alzheimer Disease.

    Science.gov (United States)

    Honer, Michael; Gobbi, Luca; Knust, Henner; Kuwabara, Hiroto; Muri, Dieter; Koerner, Matthias; Valentine, Heather; Dannals, Robert F; Wong, Dean F; Borroni, Edilio

    2018-04-01

    Tau aggregates and amyloid-β (Aβ) plaques are key histopathologic features in Alzheimer disease (AD) and are considered targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. This article describes the preclinical in vitro and in vivo characterization of 3 novel compounds-RO6958948, RO6931643, and RO6924963-that bind specifically to tau aggregates and have the potential to become PET tracers for future human use. Methods: RO6958948, RO6931643, and RO6924963 were identified as high-affinity competitors at the 3 H-T808 binding site on native tau aggregates in human late-stage AD brain tissue. Binding of tritiated compounds to brain tissue sections of AD patients and healthy controls was analyzed by macro- and microautoradiography and by costaining of tau aggregates and Aβ plaques on the same tissue section using specific antibodies. All 3 tracer candidates were radiolabeled with a PET nuclide and tested in vivo in tau-naïve baboons to assess brain uptake, distribution, clearance, and metabolism. Results: 3 H-RO6958948, 3 H-RO6931643, and 3 H-RO6924963 bound with high affinity and specificity to tau aggregates, clearly lacking affinity for concomitant Aβ plaques in human AD Braak V tissue sections. The specificity of all 3 radioligands for tau aggregates was supported, first, by binding patterns in AD sections comparable to the tau-specific radioligand 3 H-T808; second, by very low nonspecific binding in brain tissue devoid of tau pathology, excluding significant radioligand binding to any other central nervous system target; and third, by macroscopic and microscopic colocalization and quantitative correlation of radioligand binding and tau antibody staining on the same tissue section. RO6958948, RO6931643, and RO6924963 were successfully radiolabeled with a PET nuclide at high specific activity, radiochemical purity, and yield. After intravenous administration of 18 F-RO6958948, 11 C-RO6931643, and 11 C-RO6924963 to

  8. In vivo evaluation of PEGylated 64Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

    International Nuclear Information System (INIS)

    Petersen, Anncatrine Luisa; Andresen, Thomas Lars; Henriksen, Jonas Rosager; Binderup, Tina; Hag, Anne Mette; Kjaer, Andreas; Elema, Dennis Ringkjoebing; Rasmussen, Palle Hedengran

    2016-01-01

    The objective of this study was to evaluate the potential of PEGylated 64 Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated 177 Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and 64 Cu- and 177 Lu-loading efficiency. The tumor imaging potential of 64 Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The 64 Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of 177 Lu-liposomes. High remote loading efficiency (>95 %) was obtained for both 64 Cu and 177 Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the 64 Cu-liposomes estimated an acceptable total effective dose of 3.3.10 -2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177 Lu-liposomes. The overall preclinical profile of PEGylated 64 Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of 64 Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated 64 Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for 177 Lu-liposomes and the preliminary

  9. In vivo evaluation of PEGylated {sup 64}Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Anncatrine Luisa; Andresen, Thomas Lars [Technical University of Denmark, Department of Micro- and Nanotechnology, Lyngby (Denmark); Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Henriksen, Jonas Rosager [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Department of Chemistry, Lyngby (Denmark); Binderup, Tina; Hag, Anne Mette; Kjaer, Andreas [University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Elema, Dennis Ringkjoebing [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark); Rasmussen, Palle Hedengran [Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark)

    2016-05-15

    The objective of this study was to evaluate the potential of PEGylated {sup 64}Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated {sup 177}Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and {sup 64}Cu- and {sup 177}Lu-loading efficiency. The tumor imaging potential of {sup 64}Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The {sup 64}Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of {sup 177}Lu-liposomes. High remote loading efficiency (>95 %) was obtained for both {sup 64}Cu and {sup 177}Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the {sup 64}Cu-liposomes estimated an acceptable total effective dose of 3.3.10{sup -2} mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic {sup 177}Lu-liposomes. The overall preclinical profile of PEGylated {sup 64}Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of {sup 64}Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated {sup 64}Cu-liposomes in a clinical research programme. The high absorbed tumor dose

  10. Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA- 714, and 11C-PK11195 in a Rat Model of Acute Neuro-inflammation

    International Nuclear Information System (INIS)

    Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B.; Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B.; Chauveau, F.; Boutin, H.; James, M.; Kassiou, M.; Kassiou, M.

    2009-01-01

    Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, 11 C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and 18 F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: 11 C-DPA-713 and 18 F-DPA-714, as well as the classic radioligand 11 C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: 11 C-DPA-713 and 18 F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, 18 F-DPA-714 performed better than 11 C-DPA-713 and 11 C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: 18 F-DPA-714 appears to be an attractive alternative to 11 C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with 18 F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. 18 F-DPA-714 will be further evaluated in longitudinal studies of neuro-inflammatory conditions such as are encountered in stroke or neuro

  11. Radioligand imaging of α4β2* nicotinic acetylcholine receptors in Alzheimer’s disease and Parkinson’s disease

    International Nuclear Information System (INIS)

    Meyer, P. M.; Tiepolt, S.; Barthel, H.; Hesse, S.; Sabri, O.

    2014-01-01

    The α4β2 * nicotinic acetylcholine receptors (α4β2 * -nAChR) are highly abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as memory, learning and attention as well as mood and motor function. Post mortem studies suggest that abnormalities of α4β2 * -nAChRs are closely linked to histopathological hallmarks of Alzheimer’s disease (AD), such as amyloid aggregates/oligomers and tangle pathology and of Parkinson’s disease (PD) such as Lewy body pathology and the nigrostriatal dopaminergic deficit. In this review we summarize and discuss nicotinic receptor imaging findings of 2-[18F]FA-85380 PET, [ 11 C]nicotine PET and 5-[ 123 I]IA-85380 SPECT studies investigating α4β2 * -nAChR binding in vivo and their relationship to mental dysfunction in the brain of patients with AD and patients out of the spectrum of Lewy body disorders such as PD and Lewy body dementia (DLB). Furthermore, recent developments of novel α4β2*-nAChR-specific PET radioligands, such as (-)[ 18 F]Flubatine or [ 18 F]AZAN are summarized. We conclude that α4β2*-nAChR-specific PET might become a biomarker for early diagnostics and drug developments in patients with AD, DLB and PD, even at early or prodromal stages.

  12. Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M{sub 1} and M{sub 2} muscarinic acetylcholine receptors in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Bergstroem, K.A. [Dept. of Clinical Neuroscience, Psychiatry and Nuclear Medicine Sections, Karolinska Institutet, Karolinska Hospital, Stockholm (Sweden); Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio (Finland); Halldin, C.; Okubo, Yoshiro; Nobuhara, Kenji; Swahn, C.G.; Karlsson, P.; Larsson, S.; Schnell, P.O.; Farde, L. [Dept. of Clinical Neuroscience, Psychiatry and Nuclear Medicine Sections, Karolinska Institutet, Karolinska Hospital, Stockholm (Sweden); Savonen, A.; Hiltunen, Jukka [MAP Medical Technologies Oy, Tikkakoski (Finland); McPherson, D.; Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Laboratory (ORNL), TN (United States)

    1999-11-01

    Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-{alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (Z-IQNP) has high affinity to the M{sub 1}and M {sub 2} muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[ {sup 123}I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[ {sup 123}I]IQNP binding in all these regions. The percentage of unchanged Z-[ {sup 123}I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[ {sup 123}I]IQNP showed higher uptake in M {sub 2}-rich regions, compared with previously obtained results with E-[ {sup 123}I]IQNP. In conclusion, the radioactivity distribution from Z-[ {sup 123}I]IQNP in monkey brain indicates that Z-[ {sup 123}I]IQNP binds to the M {sub 1}- and M {sub 2}-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET. (orig.)

  13. Synthesis of 1-[11C]-D,L-homocysteine thiolactone: a potential tracer for myocardial ischemia using PET

    International Nuclear Information System (INIS)

    Hamacher, K.; Hanus, J.

    1989-01-01

    The synthesis of 1-[ 11 C]-D,L-homocysteine thiolactone, a potential tracer for PET imaging of ischemic heart regions, is described. The labelling is achieved by reaction of [ 11 C]carbon dioxide with α-lithiated S-(tetrahydro-pyran-2-yl)3-thiopropylisonitrile. Deprotection of the mercapto group and lactonisation of the resulting thioamino acid is accomplished in an acid catalysed reaction. The radiochemical yield obtained is 10 to 15% and the synthesis time, including the HPLC purification is about 45 min. (author)

  14. Characterization of membrane potential-dependent uptake of the novel PET tracer 18F-fluorobenzyl triphenylphosphonium cation

    International Nuclear Information System (INIS)

    Madar, Igal; Ravert, Hayden; Abro, Masroor; Pomper, Martin; Dannals, Robert; Frost, James J.; Nelkin, Barry

    2007-01-01

    Mitochondrial dysfunction has been attributed a critical role in the etiology and pathogenesis of numerous diseases, and is manifested by alterations of the organelle's membrane potential (Δψ m ). This suggests that Δψ m measurement can be highly useful for diagnostic purposes. In the current study, we characterized the capability of the novel PET agent 18 F-fluorobenzyl triphenylphosphonium ( 18 F-FBnTP) to assess Δψ m , compared with the well-established voltage sensor 3 H-tetraphenylphosphonium ( 3 H-TPP). 18 F-FBnTP and 3 H-TPP uptake under conditions known to alter Δψ m and plasma membrane potential (Δψ p ) was assayed in the H345 lung carcinoma cell line. 18 F-FBnTP biodistribution was assessed in CD1 mice using dynamic PET and ex vivo gamma well counting. 18 F-FBnTP and 3 H-TPP demonstrated similar uptake kinetics and plateau concentrations in H345 cells. Stepwise membrane depolarization resulted in a linear decrease in 18 F-FBnTP cellular uptake, with a slope (-0.58±0.06) and correlation coefficient (0.94±0.07) similar (p>0.17) to those measured for 3 H-TPP (-0.63±0.06 and 0.96±0.05, respectively). Selective collapse of Δψ m caused a substantial decrease in cellular uptake for 18 F-FBnTP (81.6±8.1%) and 3 H-TPP (85.4±6.7%), compared with control. Exposure to the proapoptotic staurosporine, known to collapse Δψ m , resulted in a decrease of 68.7±10.1% and 71.5±8.4% in 18 F-FBnTP and 3 H-TPP cellular uptake, respectively. 18 F-FBnTP accumulated mainly in kidney, heart and liver. 18 F-FBnTP is a mitochondria-targeting PET radiopharmaceutical responsive to alterations in membrane potential with voltage-dependent performance similar to that of 3 H-TPP. 18 F-FBnTP is a promising new voltage sensor for detection of physiological and pathological processes associated with mitochondrial dysfunction, such as apoptosis, using PET. (orig.)

  15. Serotonin-1A receptors in major depression quantified using PET: controversies, confounds, and recommendations.

    Science.gov (United States)

    Shrestha, Saurav; Hirvonen, Jussi; Hines, Christina S; Henter, Ioline D; Svenningsson, Per; Pike, Victor W; Innis, Robert B

    2012-02-15

    The serotonin-1A (5-HT(1A)) receptor is of particular interest in human positron emission tomography (PET) studies of major depressive disorder (MDD). Of the eight studies investigating this issue in the brains of patients with MDD, four reported decreased 5-HT(1A) receptor density, two reported no change, and two reported increased 5-HT(1A) receptor density. While clinical heterogeneity may have contributed to these differing results, methodological factors by themselves could also explain the discrepancies. This review highlights several of these factors, including the use of the cerebellum as a reference region and the imprecision of measuring the concentration of parent radioligand in arterial plasma, the method otherwise considered to be the 'gold standard'. Other potential confounds also exist that could restrict or unexpectedly affect the interpretation of results. For example, the radioligand may be a substrate for an efflux transporter - like P-gp - at the blood-brain barrier; furthermore, the binding of the radioligand to the receptor in various stages of cellular trafficking is unknown. Efflux transport and cellular trafficking may also be differentially expressed in patients compared to healthy subjects. We believe that, taken together, the existing disparate findings do not reliably answer the question of whether 5-HT(1A) receptors are altered in MDD or in subgroups of patients with MDD. In addition, useful meta-analysis is precluded because only one of the imaging centers acquired all the data necessary to address these methodological concerns. We recommend that in the future, individual centers acquire more thorough data capable of addressing methodological concerns, and that multiple centers collaborate to meaningfully pool their data for meta-analysis. Published by Elsevier Inc.

  16. In vivo assessment of [11C]MRB as a prospective PET ligand for imaging the norepinephrine transporter

    International Nuclear Information System (INIS)

    Severance, Alin J.; Milak, Matthew S.; Dileep Kumar, J.S.; Arango, Victoria; Parsey, Ramin V.; Prabhakaran, Jaya; Majo, Vattoly J.; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J.J.

    2007-01-01

    Antagonism of norepinephrine reuptake is now an important pharmacological strategy in the treatment of anxiety and depressive disorders, and many antidepressants have substantial potential occupancy of the norepinephrine transporter (NET) at recommended dosages. Despite the importance of understanding this transporter's role in psychiatric disease and treatment, a suitable radioligand for studying NET has been slow to emerge. (S,S)-Methylreboxetine (MRB) is among the more promising ligands recently adapted for positron emission tomography (PET), and the present study aimed to evaluate its potential for use in higher primates. Affinities for various brain targets were determined in vitro. PET studies were conducted in baboon under both test-retest and blocking conditions using 1 mg/kg nisoxetine. MRB has sixfold higher affinity for NET than the serotonin transporter, and negligible affinity for other sites. PET studies in baboons showed little regional heterogeneity in binding and were minimally affected by pretreatment with the NET antagonist nisoxetine. Despite improvement over previous ligands for imaging NET in vivo, the low signal to noise ratio indicates [ 11 C]MRB lacks sensitivity and reliability as a PET radiotracer in humans. (orig.)

  17. Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? – From Chinese healthcare system perspective

    International Nuclear Information System (INIS)

    Wang, Yu-ting; Huang, Gang

    2012-01-01

    Objectives: The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Methods: Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Results: Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800 RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B–A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B–A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. Conclusions: The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making.

  18. Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? - From Chinese healthcare system perspective

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu-ting, E-mail: wangyuting_330@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (China); Huang, Gang, E-mail: huang2802@163.com [Department of Nuclear Medicine, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (China); Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences - CAS (China)

    2012-08-15

    Objectives: The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Methods: Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Results: Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800 RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B-A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B-A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. Conclusions: The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making.

  19. Is FDG PET/CT cost-effective for pre-operation staging of potentially operative non-small cell lung cancer? - From Chinese healthcare system perspective.

    Science.gov (United States)

    Wang, Yu-ting; Huang, Gang

    2012-08-01

    The remarkable morbidity and mortality of lung cancer in the large population address major economic challenges to Chinese healthcare system. This study aims to assess the cost-effectiveness of fluorodeoxyglucose positron emission tomography (FDG PET)/CT for staging patients with non-small cell lung cancer (NSCLC) in China. Management of potentially operative NSCLC was modeled on decision analysis employing data in China. The strategies compared were conventional CT staging (strategy A), additional PET/CT in all patients (strategy B) or only in patients with normal-sized lymph nodes on CT (strategy C). Published medical data for Chinese patients was extracted. The costs corresponded to reimbursement by Chinese public health provider in 2010. Uncertainly of employed parameters was calculated in sensitivity analysis. Taking strategy A as baseline, the incremental cost-effectiveness ratio (ICER) of strategy B was 23,800RMB ($3500) per life year saved, which was acceptable in views of a developing country as China; while strategy C exhibited some loss of life years. Sensitivity analysis suggested the ICER (B-A) was raised more remarkably by a deterioration of PET specificity than by that of its sensitivity. The ICER was turned negative by PET specificity lower than 0.79. Economically, PET cost was proportional to the ICER (B-A), and decrease of palliative therapy cost could reduce both the ICER and overall cost. The PET/CT strategy is potentially cost-effective for management of NSCLC in China. Patients with nodal-positive CT results are not suggested to be excluded from further PET/CT. Furthermore, maintaining high specificity of PET in clinical scenarios is crucial. Prospective trials are warranted to transfer these results into policy making. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Read the Label First: Protect Your Pets

    Science.gov (United States)

    Learn about the importance of reading pet products labels before purchasing and using any product to insure the safety of your pets. Find tips for ways to reduce the changes of pets accessing potentially dangerous products.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  2. The Z-isomer of 11 beta-methoxy-17 alpha-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

    NARCIS (Netherlands)

    Rijks, L. J.; Boer, G. J.; Endert, E.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1997-01-01

    The potential of both stereoisomers of 11 beta-methoxy-17 alpha-[123I] iodovinylestradiol (E- and Z-[123I]MIVE) as suitable radioligands for imaging of estrogen receptor (ER)-positive human breast tumours was studied. The 17 alpha-[123I]iodovinylestradiol derivatives were prepared stereospecifically

  3. (11)C-MK-8278 PET as a tool for pharmacodynamic brain occupancy of histamine 3 receptor inverse agonists.

    Science.gov (United States)

    Van Laere, Koenraad J; Sanabria-Bohórquez, Sandra M; Mozley, David P; Burns, Donald H; Hamill, Terence G; Van Hecken, Anne; De Lepeleire, Inge; Koole, Michel; Bormans, Guy; de Hoon, Jan; Depré, Marleen; Cerchio, Kristine; Plalcza, John; Han, Lingling; Renger, John; Hargreaves, Richard J; Iannone, Robert

    2014-01-01

    The histamine 3 (H3) receptor is a presynaptic autoreceptor in the central nervous system that regulates the synthesis and release of histamine and modulates the release of other major neurotransmitters. H3 receptor inverse agonists (IAs) may be efficacious in the treatment of various central nervous system disorders, including excessive daytime sleepiness, attention deficit hyperactivity disorder, Alzheimer disease, ethanol addiction, and obesity. Using PET and a novel high-affinity and selective radioligand (11)C-MK-8278, we studied the tracer biodistribution, quantification, and brain H3 receptor occupancy (RO) of MK-0249 and MK-3134, 2 potential IA drugs targeting cerebral H3 receptors, in 6 healthy male subjects (age, 19-40 y). The relationship among H3 IA dose, time on target, and peripheral pharmacokinetics was further investigated in 15 healthy male volunteers (age, 18-40 y) with up to 3 PET scans and 3 subjects per dose level. The mean effective dose for (11)C-MK-8278 was 5.4 ± 1.1 μSv/MBq. Human brain kinetics showed rapid high uptake and fast washout. Binding potential values can be assessed using the pons as a reference region, with a test-retest repeatability of 7%. Drug RO data showed low interindividual variability per dose (mean RO SD, 2.1%), and a targeted 90% RO can be reached for both IAs at clinically feasible doses. (11)C-MK-8278 is a useful novel PET radioligand for determination of human cerebral H3 receptor binding and allows highly reproducible in vivo brain occupancy of H3-targeting drugs, hereby enabling the evaluation of novel compounds in early development to select doses and schedules.

  4. Cellulose nanocrystals obtained from office waste paper and their potential application in PET packing materials.

    Science.gov (United States)

    Lei, Wanqing; Fang, Changqing; Zhou, Xing; Yin, Qian; Pan, Shaofei; Yang, Rong; Liu, Donghong; Ouyang, Yun

    2018-02-01

    Annually a tremendous amount of office waste paper (OWP) is discarded creating environmental pollution. Therefore, how to make this paper from waste to wealth and use it in new approaches have become a meaningful and challenging work. In this work, OWP being a cellulose rich biomass was employed for the production of cellulose nanocrystals (CNCs) by acid hydrolysis with different acid concentrations but without subjecting OWP to alkali and bleaching treatments. The testing results showed that CNCs prepared using sulfuric acid concentration of 59% with respect to OWP had the highest crystallinity and this concentration was the transition concentration for the production of opaque CNCs film with convoluted nanofibers to transparent one with orientated nanofibers. Besides, CNCs prepared using acid concentration of 65% coated on PET sheet not only had a better water vapor barrier property but also was on a par with the transparency of PET, which was hopeful to be used as coating materials in packaging materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. In vivo imaging of neuroinflammation in the rodent brain with [{sup 11}C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, Fabien [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Universite Lyon 1, Creatis, CNRS UMR 5220, INSERM U630, INSA Lyon, Lyon (France); Boutin, Herve [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Camp, Nadja van; Tavitian, Bertrand [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Thominiaux, Cyrille; Dolle, Frederic [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Hantraye, Philippe [CEA, DSV, IBM, MIRCEN, Fontenay-aux-Roses (France); Rivron, Luc [Sanofi-Aventis, GMPK-Global Isotope Chemistry and Metabolite Synthesis Department (ICMS), Paris (France); Marguet, Frank; Castel, Marie-Noelle; Rooney, Thomas; Benavides, Jesus [Sanofi-Aventis, CNS Department, Paris (France)

    2011-03-15

    Neuroinflammation is involved in neurological disorders through the activation of microglial cells. Imaging of neuroinflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive biomarker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuroprotective effects. Here we report the radiolabelling of SSR180575 with {sup 11}C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats. The image contrast and the binding of [{sup 11}C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [{sup 11}C]PK11195. Competition studies demonstrate that [{sup 11}C]SSR180575 has high specific binding for the TSPO. [{sup 11}C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuroinflammation in animal models and in the clinic. (orig.)

  6. Cerebral monoamine oxidase A inhibition in tobacco smokers confirmed with PET and [11C]Befloxatone

    International Nuclear Information System (INIS)

    Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch.; Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch.; Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch.; Berlin, I.; Gregoire, M.C.; Bottlaender, M.; Roumenov, D.; Dolle, F.; Bourgeois, S.; Artiges, E.; Trichard, Ch.

    2009-01-01

    The inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [ 11 C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [ 11 C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco. (authors)

  7. CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Ganeshan, B.; Miles, K.A.; Shortman, R.; Afaq, A.; Ardeshna, K.M.; Groves, A.M.; Kayani, I.; Babikir, S.

    2017-01-01

    The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. (orig.)

  8. Dual time point FDG-PET/CT imaging...; Potential tool for diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Zytoon, A.A.; Murakami, K.; El-Kholy, M.R.; El-Shorbagy, E.

    2008-01-01

    Aim: This prospective study was designed to assess the utility of the dual time point imaging technique using 2- [ 18 F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) to detect primary breast cancer and to determine whether it is useful for the detection of small and non-invasive cancers, as well as cancers in dense breast tissue. Methods: One hundred and eleven patients with newly diagnosed breast cancer underwent two sequential PET/CT examinations (dual time point imaging) for preoperative staging. The maximum standardized uptake value (SUVmax) of FDG was measured from both time points. The percentage change in SUVmax (ΔSUVmax%) between time points 1 (SUVmax1) and 2 (SUVmax2) was calculated. The patients were divided into groups: invasive (n = 82), non invasive (n = 29); large (>10 mm; n = 80), small (≤10 mm; n = 31); tumours in dense breasts (n = 61), and tumours in non-dense breasts (n = 50). The tumour:background (T:B) ratios at both time points were measured and the ΔSUVmax%, ΔT:B% values were calculated. All PET study results were correlated with the histopathology results. Results: Of the 111 cancer lesions, 88 (79.3%) showed an increase and 23 (20.7%) showed either no change [10 (9%)] or a decrease [13 (11.7%)] in the SUVmax over time. Of the 111 contralateral normal breasts, nine (8.1%) showed an increase and 102 (91.9%) showed either no change [17 (15.3%)] or a decrease [85 (76.6%)] in the SUVmax over time. The mean ± SD of SUVmax1, SUVmax2, Δ%SUVmax were 4.9 ± 3.6, 6.0 ± 4.5, and 22.6 ± 13.1% for invasive cancers, 4.1 ± 3.8, 4.4 ± 4.8, and -2.4 ± 18.5% for non-invasive cancers, 2.3 ± 1.9, 2.7 ± 2.3, and 12.9 ± 21.1% for small cancers, 5.6 ± 3.7, 6.8 ± 4.8, and 17.3 ± 17.1% for large cancers, 4.9 ± 3.7, 5.8 ± 4.8, and 15.1 ± 17.6% for cancers in dense breast, and 4.5 ± 3.6, 5.4 ± 4.5, and 17.2 ± 19.2% for cancers in non-dense breast. The receiver-operating characteristic (ROC) analysis

  9. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

    International Nuclear Information System (INIS)

    Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H.; Ted Treves, S.; Packard, Alan B.

    2010-01-01

    There is considerable interest in developing an 18 F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99m Tc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18 F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99m Tc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18 F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18 F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2'-[ 18 F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [ 18 F]fluoroethyltosylate in acetonitrile at 165 deg. C for 30 min using [ 18 F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K 2 CO 3 , and [ 18 F]NaF in acetonitrile for 10 min at 90 deg. C. The product was purified by semi-preparative HPLC to produce the 2'-[ 18 F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min.

  10. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

    Science.gov (United States)

    Heinrich, Tobias K.; Gottumukkala, Vijay; Snay, Erin; Dunning, Patricia; Fahey, Frederic H; Treves, S. Ted; Packard, Alan B.

    2009-01-01

    There is considerable interest in developing an 18F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with 99mTc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an 18F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like 99mTc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether 18F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the 18F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2′-[18F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [18F]fluoroethyltosylate in acetonitrile at 165°C for 30 min.using [18F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K2CO3, and [18F]NaF in acetonitrile for 10 min. at 90°C. The product was purified by semi-preparative HPLC to produce the 2′-[18F]-fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/μmol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min. PMID:19783150

  11. Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich, Tobias K.; Gottumukkala, Vijay [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Snay, Erin; Dunning, Patricia [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Fahey, Frederic H.; Ted Treves, S. [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Packard, Alan B. [Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, 300 Longwood Ave., Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States)], E-mail: alan.packard@childrens.harvard.edu

    2010-01-15

    There is considerable interest in developing an {sup 18}F-labeled PET myocardial perfusion agent. Rhodamine dyes share several properties with {sup 99m}Tc-MIBI, the most commonly used single-photon myocardial perfusion agent, suggesting that an {sup 18}F-labeled rhodamine dye might prove useful for this application. In addition to being lipophilic cations, like {sup 99m}Tc-MIBI, rhodamine dyes are known to accumulate in the myocardium and are substrates for Pgp, the protein implicated in MDR1 multidrug resistance. As the first step in determining whether {sup 18}F-labeled rhodamines might be useful as myocardial perfusion agents for PET, our objective was to develop synthetic methods for preparing the {sup 18}F-labeled compounds so that they could be evaluated in vivo. Rhodamine B was chosen as the prototype compound for development of the synthesis because the ethyl substituents on the amine moieties of rhodamine B protect them from side reactions, thus eliminating the need to include (and subsequently remove) protecting groups. The 2'-[{sup 18}F]fluoroethyl ester of rhodamine B was synthesized by heating rhodamine B lactone with [{sup 18}F]fluoroethyltosylate in acetonitrile at 165 deg. C for 30 min using [{sup 18}F]fluoroethyl tosylate, which was prepared by the reaction of ethyleneglycol ditosylate with Kryptofix 2.2.2, K{sub 2}CO{sub 3}, and [{sup 18}F]NaF in acetonitrile for 10 min at 90 deg. C. The product was purified by semi-preparative HPLC to produce the 2'-[{sup 18}F]fluoroethylester in >97% radiochemical purity with a specific activity of 1.3 GBq/{mu}mol, an isolated decay corrected yield of 35%, and a total synthesis time of 90 min.

  12. Adenosine A{sub 2A} receptor imaging with [{sup 11}C]KF18446 PET in the rat brain after quinolinic acid lesion. Comparison with the dopamine receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi; Ogi, Nobuo; Hayakawa, Nobutaka [Tokyo Metropolitan Inst. of Gerontology, Tokyo (Japan). Positron Medical Center] [and others

    2002-11-01

    We proposed [{sup 11}C]KF18446 as a selective radioligand for mapping the adenosine A{sub 2A} receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [{sup 11}C]KF18446 PET can detect the change in the striatal adenosine A{sub 2A} receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [{sup 11}C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [{sup 11}C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [{sup 11}C] raclopride binding to dopamine D{sub 2} receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [{sup 11}C]SCH23390 binding to dopamine D{sub 1} receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [{sup 11}C]KF18446 PET can detect change in the adenosine A{sub 2A} receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum. (author)

  13. [{sup 18}F]DPA-714, [{sup 18}F]PBR111 and [{sup 18}F]FEDAA1106-Selective radioligands for imaging TSPO 18 kDa with PET: Automated radiosynthesis on a TRACERLAb FX-FN synthesizer and quality controls

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnast, Bertrand, E-mail: bertrand.kuhnast@cea.fr [CEA, I2BM, Service Hospitalier Frederic Joliot, 4 Place du General Leclerc, F-91401, Orsay Cedex (France); Damont, Annelaure; Hinnen, Francoise; Catarina, Tony; Demphel, Stephane; Le Helleix, Stephane; Coulon, Christine; Goutal, Sebastien; Gervais, Philippe; Dolle, Frederic [CEA, I2BM, Service Hospitalier Frederic Joliot, 4 Place du General Leclerc, F-91401, Orsay Cedex (France)

    2012-03-15

    Imaging of TSPO 18 kDa with PET is more and more considered as a relevant biomarker of inflammation in numerous diseases. Development of new radiotracers for TSPO 18 kDa has seen acceleration in the last years and the challenge today is to make available large amounts of such a radiotracer in compliance with GMP standards for application in humans. We present in this technical note automated productions of [{sup 18}F]DPA-714, [{sup 18}F]PBR111 and [{sup 18}F]FEDAA1106, three promising radiotracers for TSPO 18 kDa imaging, using a TRACERlab FX-FN synthesizer. This note also includes the quality control data of the validation batches for the manufacturing qualification of clinical production of [{sup 18}F]DPA-714. - Highlights: Black-Right-Pointing-Pointer Protein TSPO 18 kDa is recognized as a biomarker of inflammation involved in many diseases. Black-Right-Pointing-Pointer Radiotracers targeting TSPO prepared in compliance with GMPs are mandatory as new imaging tools. Black-Right-Pointing-Pointer An automated radiosynthesis of promising radiotracers and full QC have been implemented.

  14. MO-AB-BRA-06: Dynamic FLT PET for Investigating Potential Synergistic Therapeutic Targets During Anti-Angiogenic Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Scarpelli, M; Perlman, S; Liu, G [University of Wisconsin-Madison, Madison, WI (United States); Simoncic, U [Jozef Stefan Institute, Ljubljana (Slovenia); Jeraj, R [University of Wisconsin-Madison, Madison, WI (United States); Jozef Stefan Institute, Ljubljana (Slovenia)

    2016-06-15

    Purpose: Novel treatment strategies for metastatic cancer patients involve synergistically combining treatments with the hope of improving outcomes. This study investigated changes in tumor proliferative and vascular characteristics derived from dynamic [F-18]FLT PET during antiangiogenic treatment with the goal of identifying synergistic treatment opportunities. Methods: Patients with various solid cancers underwent continuous three-week cycles of anti-angiogenic treatment with intermittent dosing (two-weeks-on/one-week-off). Patients received up to six dynamic FLT PET/CT scans (days 0, 14, and 21 of cycle 1 (C1) and cycle 3 (C3)). Tumor proliferative (Kflt, net uptake rate) and vascular parameters (K1 blood-to-tissue transfer; Vb, vascular fraction) were calculated using a two-tissue compartment four-rate parameter kinetic model. Relative changes in these parameters, from day 0 to 14 (TxResp) and day 14 to 21 (offTxResp), were calculated. Significant differences were tested using Wilcoxon signed-rank test and significant correlations were tested using Spearman correlation. Results: Thirty patients were evaluable for C1 offTxResp with median values for Kflt, K1, and Vb of +30%, +35% and +30%, respectively. The fractions of patients with positive C1 offTxResp were: 21/30 for Ki, 24/30 for K1, 21/30 for Vb, and 12/30 had positive offTxResp for all three kinetic parameters. The offTxResp in C3 was not significantly different from C1 for any of the kinetic parameters. Significant correlations were found between TxResp and offTxResp in C1 for Kflt (ρ=-0.52, p=0.014), K1 (ρ=−0.61, p=0.003) and Vb (ρ=−0.80, p<0.001). Similar correlations were found for Kflt (ρ=-1, p=0.017) and K1 (ρ=−1, p=0.017) for the five patients evaluable in C3. Conclusion: Dynamic FLT PET showed evidence of distinct vascular and proliferative increases during off treatment weeks that could potentially be targeted with synergistic therapy. Early changes in kinetic parameters were

  15. Cardiac sympathetic neuronal imaging using PET

    International Nuclear Information System (INIS)

    Lautamaeki, Riikka; Tipre, Dnyanesh; Bengel, Frank M.

    2007-01-01

    Balance of the autonomic nervous system is essential for adequate cardiac performance, and alterations seem to play a key role in the development and progression of various cardiac diseases. PET imaging of the cardiac autonomic nervous system has advanced extensively in recent years, and multiple pre- and postsynaptic tracers have been introduced. The high spatial and temporal resolution of PET enables noninvasive quantification of neurophysiologic processes at the tissue level. Ligands for catecholamine receptors, along with radiolabeled catecholamines and catecholamine analogs, have been applied to determine involvement of sympathetic dysinnervation at different stages of heart diseases such as ischemia, heart failure, and arrhythmia. This review summarizes the recent findings in neurocardiological PET imaging. Experimental studies with several radioligands and clinical findings in cardiac dysautonomias are discussed. (orig.)

  16. Synthesis of 18F labeled clotrimazole derivatives as a potential PET imaging agent

    International Nuclear Information System (INIS)

    Jung, Soon Jae; Kim, In Jong; Park, Jeong Hoon; Lee, Heung Nae; Kim, Sang Wook; Hur, Min Goo; Choi, Sang Moo; Yang, Seung Dae; Yu, Kook Hyun

    2010-01-01

    Clotrimazole [1- -1H-imidazole, CLT] has been reported to inhibit the proliferation of vascular endothelial and act as an in vitro anti-VEGF drug. It is also shown to inhibit angiogenesis in an animal model. The radioisotope labeled clotrimazole derivative can be utilized to monitor the physiologic processes of cancer. In this study, we synthesized [ 18 F]fluoride labeled clotrimazole derivatives as a new tumor imaging agent for PET. The references were prepared by a refluxing with clotrimazole and an excess of fluoroalkyltosylate in acetonitrile for 36 h and clotrimazole reacted with ditosylalkane to give precursors. [ 18 ]Fluoride labeled reaction was performed with precursor in Kryptofix[2.2.2]/K 2 CO 3 for 10 min at 80 .deg. C. The radiolabeling mixture was passed through a silica Sep-Pak cartridge to remove 18 F - . The [ 18 ]F-clotrimazole derivatives were synthesized with a 20 ∼ 25% yield. In the radiofluoriantion step, we used acetonitrile and DMSO as a solvent and observed a higher at the acetonitrile (25%) reaction compared with the DMSO reaction (5%)

  17. Localization and prediction of malignant potential in recurrent pheochromocytoma/paraganglioma (PCC/PGL) using 18F-FDG PET/CT.

    Science.gov (United States)

    Fikri, Ahmad Saad Fathinul; Kroiss, A; Ahmad, A Z F; Zanariah, H; Lau, W F E; Uprimny, C; Donnemiller, E; Kendler, D; Nordin, A J; Virgolini, I J

    2014-06-01

    To our knowledge, data are lacking on the role of 18F-FDG PET/CT in the localization and prediction of neuroendocrine tumors, in particular the pheochromocytoma/paraganglioma (PCC/PGL) group. To evaluate the role of 18F-FDG PET/CT in localizing and predicting the malignant potential of PCC/PGL. Twenty-three consecutive patients with a history of PCC/PGL, presenting with symptoms related to catecholamine excess, underwent 18F-FDG PET/CT. Final confirmation of the diagnosis was made using the composite references. PET/CT findings were analyzed on a per-lesion basis and a per-patient basis. Tumor SUVmax was analyzed to predict the dichotomization of patient endpoints for the local disease and metastatic groups. We investigated 23 patients (10 men, 13 women) with a mean age of 46.43 ± 3.70 years. Serum catecholamine levels were elevated in 82.60% of these patients. There were 136 sites (mean SUVmax: 16.39 ± 3.47) of validated disease recurrence. The overall sensitivities for diagnostic CT, FDG PET, and FDG PET/CT were 86.02%, 87.50%, and 98.59%, respectively. Based on the composite references, 39.10% of patients had local disease. There were significant differences in the SUVmax distribution between the local disease and metastatic groups; a significant correlation was noted when a SUVmax cut-off was set at 9.2 (Plocalization of recurrent tumors. Tumor SUVmax is a potentially useful predictor of malignant tumor potential. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and potential toxicity.

    Science.gov (United States)

    Bach, Cristina; Dauchy, Xavier; Severin, Isabelle; Munoz, Jean-François; Etienne, Serge; Chagnon, Marie-Christine

    2013-08-15

    The purpose of this study was to investigate the impact of temperature on the release of PET-bottle constituents into water and to assess the potential health hazard using in vitro bioassays with bacteria and human cell lines. Aldehydes, trace metals and other compounds found in plastic packaging were analysed in PET-bottled water stored at different temperatures: 40, 50, and 60°C. In this study, temperature and the presence of CO2 increased the release of formaldehyde, acetaldehyde and antimony (Sb). In parallel, genotoxicity assays (Ames and micronucleus assays) and transcriptional-reporter gene assays for estrogenic and anti-androgenic activity were performed on bottled water extracts at relevant consumer exposure levels. As expected, and in accordance with the chemical formulations specified for PET bottles, neither phthalates nor UV stabilisers were present in the water extracts. However, 2,4-di-tert-butylphenol, a degradation compound of phenolic antioxidants, was detected. In addition, an intermediary monomer, bis(2-hydroxyethyl)terephthalate, was found but only in PET-bottled waters. None of the compounds are on the positive list of EU Regulation No. 10/2011. However, the PET-bottled water extracts did not induce any cytotoxic, genotoxic or endocrine-disruption activity in the bioassays after exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Synthesis, in vitro and in vivo evaluation of [11C]MMTP: a potential PET ligand for mGluR1 receptors

    DEFF Research Database (Denmark)

    Prabhakaran, Jaya; Majo, Vattoly J; Milak, Matthew S

    2010-01-01

    Synthesis, in vitro and in vivo evaluation of [O-methyl-(11)C]dimethylamino-3(4-methoxyphenyl)-3H-pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-one (1), a potential imaging agent for mGluR1 receptors using PET are described. Synthesis of the corresponding desmethyl precursor 2 was achieved...... selectively labeled mGluR1 receptors in slide-mounted sections of postmortem human brain containing cerebellum, hippocampus, prefrontal cortex and striatum as demonstrated by in vitro autoradiography using phosphor-imaging. PET studies in anesthetized baboon show that [(11)C]1 penetrates the BBB...... and accumulates in cerebellum, a region reported to have higher expression of mGluR1. These findings suggest [(11)C]1 is a promising PET radiotracer candidate for mGluR1....

  20. PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

    Science.gov (United States)

    Gewirtz, Henry

    2017-12-01

    This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

  1. Synthesis, uptake mechanism characterization and biological evaluation of {sup 18}F labeled fluoroalkyl phenylalanine analogs as potential PET imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Wang Limin [Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104 (United States); Qu Wenchao; Lieberman, Brian P.; Ploessl, Karl [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung, Hank F., E-mail: kunghf@gmail.co [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)

    2011-01-15

    Introduction: Amino acids based tracers represent a promising class of tumor metabolic imaging agents with successful clinical applications. Two new phenylalanine derivatives, p-(2-[{sup 18}F]fluoroethyl)-L-phenylalanine (FEP, [{sup 18}F]2) and p-(3-[{sup 18}F]fluoropropyl)-L-phenylalanine (FPP, [{sup 18}F]3) were synthesized and evaluated in comparison to clinically utilized O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine (FET, [{sup 18}F]1). Methods: FEP ([{sup 18}F]2) and FPP ([{sup 18}F]3) were successfully synthesized by a rapid and efficient two-step nucleophilic fluorination of tosylate precursors and deprotection reaction. In vitro cell uptake studies were carried out in 9L glioma cells. In vivo studies, 9L tumor xenografts were implanted in Fisher 344 rats. Results: FEP ([{sup 18}F]2) and FPP ([{sup 18}F]3) could be efficiently labeled within 90 min with good enantiomeric purity (>95%), good yield (11-37%) and high specific activity (21-69 GBq/{mu}mol). Cell uptake studies showed FEP had higher uptake than FPP as well as reference ligand FET ([{sup 18}F]1). Uptake mechanism studies suggested that FEP is a selective substrate for system L and prefers its subtype LAT1. In vivo biodistribution studies demonstrated FEP had specific accumulation in tumor cells and tumor to background ratio reached 1.45 at 60 min. Small animal positron emission tomography (PET) imaging studies showed FEP was comparable to FET for imaging rats bearing 9L tumor model. FEP had high uptake in 9L tumor compared to surrounding tissue and was quickly excreted through urinary tract. Conclusion: Biological evaluations indicate that FEP ([{sup 18}F]2) is a potential useful tracer for tumor imaging with PET.

  2. Can Laws Be a Potential PET Image Texture Analysis Approach for Evaluation of Tumor Heterogeneity and Histopathological Characteristics in NSCLC?

    Science.gov (United States)

    Karacavus, Seyhan; Yılmaz, Bülent; Tasdemir, Arzu; Kayaaltı, Ömer; Kaya, Eser; İçer, Semra; Ayyıldız, Oguzhan

    2018-04-01

    We investigated the association between the textural features obtained from 18 F-FDG images, metabolic parameters (SUVmax , SUVmean, MTV, TLG), and tumor histopathological characteristics (stage and Ki-67 proliferation index) in non-small cell lung cancer (NSCLC). The FDG-PET images of 67 patients with NSCLC were evaluated. MATLAB technical computing language was employed in the extraction of 137 features by using first order statistics (FOS), gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), and Laws' texture filters. Textural features and metabolic parameters were statistically analyzed in terms of good discrimination power between tumor stages, and selected features/parameters were used in the automatic classification by k-nearest neighbors (k-NN) and support vector machines (SVM). We showed that one textural feature (gray-level nonuniformity, GLN) obtained using GLRLM approach and nine textural features using Laws' approach were successful in discriminating all tumor stages, unlike metabolic parameters. There were significant correlations between Ki-67 index and some of the textural features computed using Laws' method (r = 0.6, p = 0.013). In terms of automatic classification of tumor stage, the accuracy was approximately 84% with k-NN classifier (k = 3) and SVM, using selected five features. Texture analysis of FDG-PET images has a potential to be an objective tool to assess tumor histopathological characteristics. The textural features obtained using Laws' approach could be useful in the discrimination of tumor stage.

  3. Synthesis and radiolabelling of AG957 a potential tyrphostin PET radiotracer

    International Nuclear Information System (INIS)

    Ackermann, U.; Tochon-Danguy, H.J.; Sachinidis, J.; Burgess, A.W.; Scott, A.M.

    2000-01-01

    Full text: Signalling of tyrosine kinases is a critical component of intracellular regulation of growth and function. AG957 is an inhibitor of the c-ABL tyrosine kinase found in chronic myeloid leukemia, and the labelling of AG957 with a PET radiotracer would allow for the in vivo mapping of this receptor-kinase. Synthesis of the normethyl precursor of the tyrosine kinase inhibitor AG957 has been achieved by condensation of p-amino benzoic acid with 2,6 dihydroxy benzaldehyde and subsequent reduction of the imino function with sodium cyanoborohydride. The radiolabeling of this precursor using 11 C-methyliodide in basic conditions gave unsatisfactory yields because of decomposition of the starting material. We have therefore investigated the formation of 11 C-methyl esters using 11 Cmethanol and free carboxylic acids in the presence of either trimethylsilylchloride or boron trifluoride etherate as catalyst. P-amino benzoic acid, benzoic acid and salicylic acid were used as model compounds. Boron trifluoride etherate proved to be superior to trimethylsilylchloride giving good yields of the esters of the respective carboxylic acids when reacted with 11 C-methanol at 150 deg C. However, when this method was applied to desmethyl AG957, none of the desired product was obtained due to decomposition of the precursor at high temperatures. In light of these results we are planning to investigate the irreversible transesterification of enol esters with 11 C-methanol in the presence of a tin catalyst. This reaction is known to proceed smoothly at lower temperatures and should enable us to radiolabel the tyrosine kinase inhibitor 11 C-AG957. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  4. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [{sup 11}C]PE2I in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Maria-Joao [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France)]. E-mail: maria-joao.ribeiro@cea.fr; Ricard, Marcel [Service de Physique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif (France); Lievre, Marie-Angele [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Bourgeois, Sandrine [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Emond, Patrick [INSERM U316, Laboratoire de Biophysique medicale et pharmaceutique, UFR des Sciences Pharmaceutiques, 37200 Tours (France); Gervais, Philippe [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Dolle, Frederic [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France); Syrota, Andre [Service Hospitalier Frederic Joliot, Institut d' Imagerie Biomedicale, Direction des Sciences du Vivant, Commissariat a l' Energie Atomique, F-91406 Orsay (France)

    2007-05-15

    Introduction: This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2{beta}-carbomethoxy-3{beta}-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([{sup 11}C]PE2I). [{sup 11}C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans. Methods: In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321{+-}6 MBq of [{sup 11}C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. Results: Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [{sup 11}C]PE2I was estimated to be 6.4{+-}0.6 {mu}Sv/MBq. Conclusion: The amount of [{sup 11}C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study.

  5. Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [11C]PE2I in healthy volunteers

    International Nuclear Information System (INIS)

    Ribeiro, Maria-Joao; Ricard, Marcel; Lievre, Marie-Angele; Bourgeois, Sandrine; Emond, Patrick; Gervais, Philippe; Dolle, Frederic; Syrota, Andre

    2007-01-01

    Introduction: This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy-3β-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([ 11 C]PE2I). [ 11 C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans. Methods: In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321±6 MBq of [ 11 C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. Results: Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [ 11 C]PE2I was estimated to be 6.4±0.6 μSv/MBq. Conclusion: The amount of [ 11 C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study

  6. Interference of anaesthetics with radioligand binding in neuroreceptor studies

    International Nuclear Information System (INIS)

    Elfving, Betina; Knudsen, Gitte Moos; Bjoernholm, Berith

    2003-01-01

    Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin 2A receptor and the dopamine re-uptake site by use of [ 3 H]-(S)-citalopram, [ 18 F]altanserin and [ 125 I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean ± SD) of [ 3 H]-(S)-citalopram from 1.5±0.19 to 0.81±0.19 (P 18 F]altanserin. The [ 125 I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4±0.81 to 10.1±1.4, P<0.05) and isoflurane (from 12.4±0.81 to 9.5±1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated. (orig.)

  7. Potential for pet animals to harbor methicillin-resistant Staphylococcus aureus (MRSA) when residing with human MRSA patients

    Science.gov (United States)

    Morris, Daniel O.; Lautenbach, Ebbing; Zaoutis, Theoklis; Leckerman, Kateri; Edelstein, Paul H.; Rankin, Shelley C.

    2011-01-01

    Summary Colonization by methicillin-resistant Staphylococcus aureus (MRSA) may be persistent in people, and is horizontally transmissible. The scientific literature suggests that domestic pets may also participate in cross-transmission of MRSA within households. The objectives of this study were to evaluate the prevalence of and risk factors for MRSA carriage by pets residing in households with an MRSA-infected person. From 66 households in which an MRSA infected patient resided, we screened 47 dogs and 52 cats using a swab protocol. Isolates from pets and humans were genotyped using two techniques, and compared for concordance. Human participants completed a 22-question survey of demographic and epidemiologic data relevant to staphylococcal transmission. Eleven of 99 pets (11.5%) representing 9 (13.6%) of households were MRSA-positive, but in only 6 of these households were the human and animal-source strains genetically concordant. Human infection by strain USA 100 was significantly associated with pet carriage [OR = 11.4 (95% C.I. 1.7, 76.9); p=0.013]. Yet, for each day of delay in sampling the pet after the person’s MRSA diagnosis, the odds of isolating any type of MRSA from the pet decreased by 13.9% [(95% C.I. 2.6%, 23.8%); p=0.017)]. It may be concluded that pets can harbor pandemic strains of MRSA while residing in a household with an infected person. However, the source of MRSA to the pet cannot always be attributed to the human patient. Moreover, the rapid attrition of the odds of obtaining a positive culture from pets over time suggests that MRSA carriage may be fleeting. PMID:22233337

  8. Smoking-induced dopamine release studied with [11C]raclopride PET

    International Nuclear Information System (INIS)

    Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon

    2005-01-01

    It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [ 11 C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3±2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [ 11 C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r 2 =0.91, p=0.04). These data demonstrate that in vivo imaging with [ 11 C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking

  9. Smoking-induced dopamine release studied with [{sup 11}C]raclopride PET

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Cho, Sang Soo; Lee, Do Hoon [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2005-07-01

    It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with and regulates the activation of the dopaminergic neuron. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Four male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.3{+-}2.6 years) were enrolled in this study. Dopamine D2 receptor radioligand, [{sup 11}C]raclopride was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurements of plasma nicotine levels were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as striatal-cerebellar/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean change in binding potential between the baseline and smoking in caudate, Putamen and ventral striatum was 3.7 % , 4.0 % and 8.6 %, respectively. This indicated the striatal dopamine release by smoking. The reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (r{sup 2}=0.91, p=0.04). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

  10. Cerebral monoamine oxidase A inhibition in tobacco smokers confirmed with PET and [{sup 11}C]Befloxatone

    Energy Technology Data Exchange (ETDEWEB)

    Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [INSERM U797, Research Unit ' Neuroimaging and Psychiatry' , Orsay (France); Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [CEA, ' Neuroimaging and Psychiatry, U797 Unit, Hospital Department Frederic Joliot and Neurospin (France); Leroy, C.; Bragulat, V.; Penttila, J.; Artiges, E.; Martinot, J.L.; Trichard, Ch. [Paris sud University - Paris Descartes University, UMR U797 (France); Berlin, I. [Service de Pharmacologie, Hopital Pitie-Salpetriere - Universite Paris6 - INSERM U677, Paris (France); Gregoire, M.C.; Bottlaender, M.; Roumenov, D.; Dolle, F.; Bourgeois, S. [CEA, DSV, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Artiges, E.; Trichard, Ch. [Psychiatry Department, Orsay Hospital, Orsay (France)

    2009-07-01

    The inhibition of cerebral monoamine oxidases (MAOs) by cigarette smoke components could participate to the tobacco addiction. However, the actual extent of this inhibition in vivo in smokers is still poorly known. We investigated cerebral MAO-A availability in 7 tobacco-dependent subjects and 6 healthy nonsmokers, using positron emission tomography (PET) and the MAO-A selective radioligand [{sup 11}C]befloxatone. In comparison to nonsmokers, smokers showed a significant overall reduction of [{sup 11}C]befloxatone binding potential (BP) in cortical areas (average reduction, -60%) and a similar trend in caudate and thalamus (-40%). Our findings confirm a widespread inhibition of cerebral MAO-A in smokers. This mechanism may contribute to tobacco addiction and for a possible mood-modulating effect of tobacco. (authors)

  11. Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

    Science.gov (United States)

    Guo, Shien; Getsios, Denis; Hernandez, Luis; Cho, Kelly; Lawler, Elizabeth; Altincatal, Arman; Lanes, Stephan; Blankenburg, Michael

    2012-01-01

    The growing understanding of the use of biomarkers in Alzheimer's disease (AD) may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET), is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value. PMID:23326754

  12. Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

    Directory of Open Access Journals (Sweden)

    Shien Guo

    2012-01-01

    Full Text Available The growing understanding of the use of biomarkers in Alzheimer's disease (AD may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET, is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value.

  13. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin

    2012-01-01

    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  14. A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

    Science.gov (United States)

    Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

    2016-01-01

    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89 Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans -cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64 Cu-labeled tetrazine radioligand ( 64 Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful

  15. 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

  16. Quantitative analyses of regional [{sup 11}C]PE2I binding to the dopamine transporter in the human brain: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Jucaite, Aurelija [Karolinska Institutet, Department of Woman and Child Health, Stockholm (Sweden); Odano, Ikuo [Niigata University, Department of Sensory and Integrative Medicine, Asahimachi-dori Niigata (Japan); Olsson, Hans; Pauli, Stefan; Halldin, Christer; Farde, Lars [Karolinska Institutet, Psychiatry Section, Department of Clinical Neuroscience, Stockholm (Sweden)

    2006-06-15

    The dopamine transporter (DAT) is a plasma membrane protein of central interest in the pathophysiology of neuropsychiatric disorders and is known to be a target for psychostimulant drugs. [{sup 11}C]PE2I is a new radioligand which binds selectively and with moderate affinity to central DAT, as has been demonstrated in vitro by autoradiography and in vivo by positron emission tomography (PET). The aims of the present PET study were to quantify regional [{sup 11}C]PE2I binding to DAT in the human brain and to compare quantitative methods with regard to suitability for applied clinical studies. One PET measurement was performed in each of eight healthy male subjects. The binding potential (BP) values were obtained by applying kinetic compartment analysis, which uses the metabolite-corrected arterial plasma curve as an input function. They were compared with the BP values quantified by two reference tissue approaches, using cerebellum as a reference region representing free and non-specific radioligand binding. The radioactivity concentration was highest in the striatum, lower in the midbrain and very low in the cerebellum. The regional [{sup 11}C]PE2I binding could be interpreted by kinetic compartment models. However, the BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. We suggest that the difference may be explained by the inaccurate metabolite correction, small amounts of radioactive metabolites that could account for the presence of non-specific binding in the cerebellum and insufficient data acquisition time. (orig.)

  17. The importance of small polar radiometabolites in molecular neuroimaging: A PET study with [11C]Cimbi-36 labeled in two positions.

    Science.gov (United States)

    Johansen, Annette; Hansen, Hanne D; Svarer, Claus; Lehel, Szabolcs; Leth-Petersen, Sebastian; Kristensen, Jesper L; Gillings, Nic; Knudsen, Gitte M

    2018-04-01

    [ 11 C]Cimbi-36, a 5-HT 2A receptor agonist PET radioligand, contains three methoxy groups amenable to [ 11 C]-labeling. In pigs, [ 11 C]Cimbi-36 yields a polar (M1) and a less polar (M2) radiometabolite fraction, while changing the labeling to [ 11 C]Cimbi-36_5 yields only the M1 fraction. We investigate whether changing the labeling position of [ 11 C]Cimbi-36 eliminates M2 in humans, and if this changes the signal-to-background ratio. Six healthy volunteers each underwent two dynamic PET scans; after injection of [ 11 C]Cimbi-36, both the M1 and M2 fraction appeared in plasma, whereas only the M1 appeared after [ 11 C]Cimbi-36_5 injection. [ 11 C]Cimbi-36_5 generated higher uptake than [ 11 C]Cimbi-36 in both neocortex and cerebellum. With the simplified reference tissue model mean neocortical non-displaceable binding potential for [ 11 C]Cimbi-36 was 1.38 ± 0.07, whereas for [ 11 C]Cimbi-36_5, it was 1.18 ± 0.14. This significant difference can be explained by higher non-displaceable binding caused by demethylation products in the M1 fraction such as [ 11 C]formaldehyde and/or [ 11 C]carbon dioxide/bicarbonate. Although often considered without any impact on binding measures, we show that small polar radiometabolites can substantially decrease the signal-to-background ratio of PET radioligands for neuroimaging. Further, we find that [ 11 C]Cimbi-36 has a better signal-to-background ratio than [ 11 C]Cimbi-36_5, and thus will be more sensitive to changes in 5-HT 2A receptor levels in the brain.

  18. Whole-body biodistribution and radiation dosimetry in monkeys and humans of the phosphodiesterase 4 radioligand [11C](R)-rolipram: comparison of two-dimensional planar, bisected and quadrisected image analyses

    International Nuclear Information System (INIS)

    Sprague, David R.; Fujita, Masahiro; Ryu, Yong Hoon; Liow, Jeih-San; Pike, Victor W.; Innis, Robert B.

    2008-01-01

    Introduction: [ 11 C](R)-Rolipram is a selective radioligand for positron emission tomography (PET) imaging of phosphodiesterase 4, an enzyme that metabolizes 3',5'-cyclic adenosine monophosphate. The aim of this study was to estimate the human radiation absorbed dose of the radioligand based on its biodistribution in both monkeys and humans. Methods: Whole-body PET images were acquired for 2 h after injecting [ 11 C](R)-rolipram in eight healthy humans and three monkeys. The simple method of using a single two-dimensional (2D) planar image was compared to more time-consuming methods that used two (bisected) or four (quadrisected) tomographic images in the anteroposterior direction. Results: Effective dose was 4.8 μGy/MBq based on 2D planar images. The effective dose was only slightly lower by 1% and 5% using the bisected and quadrisected images, respectively. Nevertheless, the two tomographic methods may have more accurately estimated the exposure of some organs (e.g., kidneys) that are asymmetrically located in the body or have radioactivity that appears to overlap on 2D planar images. Monkeys had a different biodistribution pattern compared to humans (e.g., greater urinary excretion) such that their data overestimated the effective dose in humans by 40%. Conclusions: The effective dose of [ 11 C](R)-rolipram was modest and comparable to that of other 11 C-labeled radioligands. The simple and far less time-consuming 2D planar method provided accurate and somewhat more conservative estimates of effective dose than the two tomographic methods. Although monkeys are commonly used to estimate human radiation exposures, their data gave a considerable overestimation for this radioligand

  19. Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor

    DEFF Research Database (Denmark)

    Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D

    2015-01-01

    We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo evaluat...... evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970....

  20. Gastrointestinal helminth parasites of pet and stray dogs as a potential risk for human health in Bahir Dar town, north-western Ethiopia

    Directory of Open Access Journals (Sweden)

    Tadiwos Abere

    Full Text Available Aim: A cross-sectional study was carried out from November 2011 to April 2012 to determine the prevalence and species of gastrointestinal (GI helminth parasites in pet and stray dogs as a potential risk for human health in Bahir Dar town, northwestern Ethiopia. Materials and Methods: A total of 384 and 46 faecal samples were collected from pet and stray dogs, respectively and xamined by using standard coprologic techniques. Results: The overall prevalence of GI helminth infection in pet and stray dogs was 75.26 and 84.78%, respectively. The detected parasites with their frequencies in pet dogs were Ancylostoma caninum (78.89%, Toxocara canis (39.79%, Dipylidium caninum (29.75%, Strongyloides stercoralis (29.06%, Taeniidae (23.87% and Trichuris vulpis (7.95%. Stray dogs were found more likely to be polyparasitized and presented higher prevalence of A. caninum, T. canis, S. stercoralis, Trichuris vulpis and Taeniidae (P < 0.05 than domiciled ones. Diphyllobothrium latum was detected only in 10.25% of stray dogs. Toxocara canis and A. caninum (P < 0.05 were detected more frequently in dogs with less than 6 months of age (P <0.05 than old age dogs. The sex or breed groups didn't significantly affect the prevalence of parasites. A significant variation was recorded (P < 0.05 between different feeding systems where higher prevalence was observed in uncontrolled feeding group (82.18% compared to controlled feeding (32.08%. Conclusion: Different gastrointestinal parasites in pet and stray dogs were identified in the study area that can potentially infect humans and cause serious public-health problems. Thus, concerted efforts should therefore be made to educate dog owners to embrace modern dog disease control programs and measures have to be taken on stray dogs. [Vet World 2013; 6(7.000: 388-392

  1. CASE REPORT PET/CT-positive brown tumour – a potentially ...

    African Journals Online (AJOL)

    Brown tumor of bone: a potential source of false-positive Thallium-201 localization. J Nucl Med 1989; 30: 1264-1267. 4. Nassar GM, Ayus JC. Images in clinical medicine. Brown tumor in end stage renal disease. N Engl J Med. 1999; 341: 1652. 5. Keyser JS, Postma GN. Brown tumor of the mandible. Am J Otolaryngol 1996; ...

  2. Interference of anaesthetics with radioligand binding in neuroreceptor studies

    Energy Technology Data Exchange (ETDEWEB)

    Elfving, Betina; Knudsen, Gitte Moos [Neurobiology Research Unit N9201, University hospital Rigshospitalet, 9 Blegdamsvej, 2100, Copenhagen (Denmark); Bjoernholm, Berith [Department of Computational Chemistry, H. Lundbeck A/S, Copenhagen-Valby (Denmark)

    2003-06-01

    Evaluations of new emission tomography ligands are usually carried out in animals. In order to keep the animals in a restricted position during the scan session, anaesthesia is almost inevitable. In ex vivo rat studies we investigated the interference of ketamine/xylazine, zoletile mixture, isoflurane and halothane with the serotonin re-uptake site, the serotonin{sub 2A} receptor and the dopamine re-uptake site by use of [{sup 3}H]-(S)-citalopram, [{sup 18}F]altanserin and [{sup 125}I]PE2I, respectively. Ketamine/xylazine decreased the target-to-background ratio (mean {+-} SD) of [{sup 3}H]-(S)-citalopram from 1.5{+-}0.19 to 0.81{+-}0.19 (P<0.05), whereas isoflurane and halothane increased the ratio from 1.5{+-}0.19 to 1.9{+-}0.24 and 2.1{+-}0.13 (P<0.05), respectively. Only with the zoletile mixture did the ratio remain unaltered. None of the tested anaesthetics affected the target-to-background ratio of [{sup 18}F]altanserin. The [{sup 125}I]PE2I target-to-background ratio decreased with both ketamine/xylazine (from 12.4{+-}0.81 to 10.1{+-}1.4, P<0.05) and isoflurane (from 12.4{+-}0.81 to 9.5{+-}1.1, P<0.05) treated rats, whereas treatment with zoletile mixture and halothane left the ratio unaltered. It is concluded that prior to performance of neuroreceptor radioligand studies, the possible interaction between radioligands and anaesthetics should be carefully evaluated. (orig.)

  3. Evaluation of 18F-labeled icotinib derivatives as potential PET agents for tumor imaging

    International Nuclear Information System (INIS)

    Hongyu Ren; Hongyu Ning; Jin Chang; Mingxia Zhao; Yong He; Yan Chong; Chuanmin Qi

    2016-01-01

    In this study, three 18 F-labeled crown ether fused anilinoquinazoline derivatives ([ 18 F]11a-c) were synthesized and evaluated as potential tumor imaging probes. The biodistribution results of [ 18 F]11b were good. Compared with [ 18 F]-fludeoxyglucose and l-[ 18 F]-fluoroethyltyrosine in the same animal model, [ 18 F]11b had better tumor/brain, tumor/muscle, and tumor/blood uptake ratios. Overall, these results suggest that [ 18 F]11b is promising as a tumor imaging agent for positron emission tomography. (author)

  4. Advances in prostate-specific membrane antigen PET of prostate cancer.

    Science.gov (United States)

    Bouchelouche, Kirsten; Choyke, Peter L

    2018-05-01

    In recent years, a large number of reports have been published on prostate-specific membrane antigen (PSMA)/PET in prostate cancer (PCa). This review highlights advances in PSMA PET in PCa during the past year. PSMA PET/computed tomography (CT) is useful in detection of biochemical recurrence, especially at low prostate-specific antigen (PSA) values. The detection rate of PSMA PET is influenced by PSA level. For primary PCa, PSMA PET/CT shows promise for tumour localization in the prostate, especially in combination with multiparametric MRI (mpMRI). For primary staging, PSMA PET/CT can be used in intermediate and high-risk PCa. Intraoperative PSMA radioligand guidance seems promising for detection of malignant lymph nodes. While the use of PSMA PET/MRI in primary localized disease is limited to high and intermediate-risk patients and localized staging, in the recurrence setting, PET/MRI can be particularly helpful when the lesions are subtle. PSMA PET/CT is superior to choline PET/CT and other conventional imaging modalities. Molecular imaging with PSMA PET continues to pave the way for personalized medicine in PCa.However, large prospective clinical studies are still needed to fully evaluate the role of PSMA PET/CT and PET/MRI in the clinical workflow of PCa.

  5. New {alpha}{sub 1}-adrenoceptor antagonists derived from the antipsychotic sertindole - carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey

    Energy Technology Data Exchange (ETDEWEB)

    Balle, Thomas E-mail: tb@dfuni.dk; Halldin, Christer; Andersen, Linus; Hjorth Alifrangis, Lene; Badolo, Lassina; Gjervig Jensen, Klaus; Chou, Y.-W.; Andersen, Kim; Perregaard, Jens; Farde, Lars

    2004-04-01

    Central {alpha}{sub 1}-adrenergic receptors are potential targets for recently developed antipsychotic drugs. Two new 11C labeled potent and selective {alpha}{sub 1}-adrenoceptor antagonists, 1- [2- [4-[1-(4-fluorophenyl)-5-(2-[{sup 11}C]methyl-tetrazol-5-yl)-1H-indol-3-yl]-1- pipridinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]2) and 1- [2- [4-[1-(4-fluorophenyl)-5-(1-[{sup 11}C]methyl-(1,2,3-triazol-4-yl) -1H-indol-3-yl]- 1-piperidinyl]ethyl]-imidazolidin-2-one ([{sup 11}C]3) were prepared and evaluated for imaging of central {alpha}{sub 1}-adrenergic receptors in the cynomolgus monkey brain. For both compounds, the total brain radioactivity was only about 0.6% of the radioactivity injected i.v. There was no evident binding in regions known to contain {alpha}{sub 1}-adrenoceptors. This observation suggests that the affinity of the radioligands in primates in vivo is not sufficient to provide a signal for specific binding that can be differentiated from the background. In addition, active efflux by P-glycoprotein may be responsible for the low total brain-uptake of the two radioligands. Both compounds showed a highly polarised and verapamile sensitive transport across monolayers of Caco-2 cells. The total brain-uptake of [{sup 3}H]2 was 6 times higher in mdr1a(-/-) knock-out mice lacking the gene encoding P-glycoprotein compared to wild type mice. Pretreatment of one monkey with Cyclosporin A (15 mg/kg) resulted in 40% higher brain uptake for [{sup 11}C]3 when compared with baseline. These observations support the view that efflux by P-glycoprotein can be of quantitative importance for the total brain-uptake of some PET radioligands.

  6. Potentials and limits of modern tomographic methods (CT, MR, PET) in molecular imaging

    International Nuclear Information System (INIS)

    Hentschel, M.; Paul, D.; Moser, E.; Brink, I.

    2007-01-01

    The present survey gives an introduction into the basics of computed tomography, magnetic resonance tomography and positron emission tomography. The current potentials of these methods in relation to their temporal, spatial and contrast resolutions as well as their sensitivities within clinical routine and experimental studies (in vitro, ex vivo) will be presented. Computed tomography constitutes the anatomical reference method with well defined contrast, high spatial resolution but low sensitivity (10 -2 mol/l) for functional and molecular imaging. Magnetic resonance tomography represents the anatomical method for research with variable tissue contrast, physiological image information, highest spatial resolution but moderate sensitivity (10 -3 -10 -5 mol/l) for functional and molecular imaging. Positron emission tomography offers good suitability for molecular imaging due to highest sensitivity (10 -11 -10 -12 mol/l). However, the spatial resolution of positron emission tomography is low. (orig.)

  7. New SPECT and PET dementia tracers

    International Nuclear Information System (INIS)

    Vergote, J.; Chalon, S.; Emond, P.; Vercouillie, J.; Guilloteau, D.; Vergote, J.; Guilloteau, D.; Pappata, J.S.

    2009-01-01

    Single photon emission tomography (SPECT) and positron emission tomography (PET) are techniques to study in vivo neurotransmitter systems, neuro inflammation and amyloid deposits in normal human brain and in dementia. These methods used to explore the integrity of dopaminergic, cholinergic and serotonergic systems in Alzheimer's disease and in other dementias allowed to understand how the neurotransmission was modified in these disorders. Progress in the understanding of pathophysiological and clinical signs of dementia requires an evolution of the radioligands used to carry out an increasingly early and differential diagnosis in addition to monitoring the progression of disease and the effects of therapies. New emerging radiotracers for neuro inflammation or amyloid deposits are essential. In this article, new SPECT and PET tracers are presented. (authors)

  8. Microfluidic radiolabeling of biomolecules with PET radiometals

    International Nuclear Information System (INIS)

    Zeng Dexing; Desai, Amit V.; Ranganathan, David; Wheeler, Tobias D.; Kenis, Paul J.A.; Reichert, David E.

    2013-01-01

    Introduction: A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. Methods: The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both 64 Cu and 68 Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Results: Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with 64 Cu/ 68 Ga using the microreactor, which demonstrates the ability to label both small and large molecules. Conclusions: A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions.

  9. Microfluidic radiolabeling of biomolecules with PET radiometals.

    Science.gov (United States)

    Zeng, Dexing; Desai, Amit V; Ranganathan, David; Wheeler, Tobias D; Kenis, Paul J A; Reichert, David E

    2013-01-01

    A robust, versatile and compact microreactor has been designed, fabricated and tested for the labeling of bifunctional chelate conjugated biomolecules (BFC-BM) with PET radiometals. The developed microreactor was used to radiolabel a chelate, either 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) that had been conjugated to cyclo(Arg-Gly-Asp-DPhe-Lys) peptide, with both ⁶⁴Cu and ⁶⁸Ga respectively. The microreactor radiolabeling conditions were optimized by varying temperature, concentration and residence time. Direct comparisons between the microreactor approach and conventional methods showed improved labeling yields and increased reproducibility with the microreactor under identical labeling conditions, due to enhanced mass and heat transfer at the microscale. More importantly, over 90% radiolabeling yields (incorporation of radiometal) were achieved with a 1:1 stoichiometry of bifunctional chelate biomolecule conjugate (BFC-BM) to radiometal in the microreactor, which potentially obviates extensive chromatographic purification that is typically required to remove the large excess of unlabeled biomolecule in radioligands prepared using conventional methods. Moreover, higher yields for radiolabeling of DOTA-functionalized BSA protein (Bovine Serum Albumin) were observed with ⁶⁴Cu/⁶⁸Ga using the microreactor, which demonstrates the ability to label both small and large molecules. A robust, reliable, compact microreactor capable of chelating radiometals with common chelates has been developed and validated. Based on our radiolabeling results, the reported microfluidic approach overall outperforms conventional radiosynthetic methods, and is a promising technology for the radiometal labeling of commonly utilized BFC-BM in aqueous solutions. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. (11)C-labeling and preliminary evaluation of vortioxetine as a PET radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2014-01-01

    . Preliminary evaluation of [(11)C]vortioxetine in a Danish Landrace pig showed rapid brain uptake and brain distribution in accordance with the pharmacological profile, all though an unexpected high binding in cerebellum was also observed. [(11)C]vortioxetine displayed slow tracer kinetics with peak uptake...

  11. PET imaging of neocortical monoaminergic terminals in Parkinson's disease

    International Nuclear Information System (INIS)

    Marie, R.M.; Barre, L.; Rioux, P.; Allain, P.; Lechevalier, B.; Baron, J.C.

    1995-01-01

    Post-mortem neurochemical studies in Parkinson's disease (PD) have shown that, in addition to the typical nigro-striatal dopamine denervation, there exists a concomitant neocortical monoamine fibre deafferentation (of variable severity) whose role in motor, and especially in associated cognitive and affective impairment, remains elusive. We have extensively examined whether PET imaging with 11 C-S-Nomifensine ( 11 C-NMF), a radioligand of the dopamine and norepinephrine presynaptic reuptake sites which has been used so far to investigate the striatum, could provide a method for assessing in vivo the neocortical monoamine terminal loss in PD; previously, this has been a little addressed and controversial issue. To this end, we prospectively selected a highly homogeneous sample of nine non-demented, non-depressed idiopathic PD patients with mild to marked side-to-side asymmetry in motor impairment. In addition to recovering the previously-reported correlations with putaminal 11 C-NMF specific uptake asymmetries, the clinical motor asymmetries also significantly correlated in the clinically expected direction to neocortical (especially frontal) 11 C-NMF asymmetries. suggesting the monoamine neocortical denervation might play a direct role in motor impairment in PD. These results demonstrate that it is possible to assess in vivo the neocortical monoamine terminal loss. and to elucidate its potential role in the complex cognitive and affective impairment, in both PD and atypical degenerative parkinsonism. (author)

  12. 90Nb: potential radionuclide for application in immuno-PET. Development of appropriate production strategy and first in vivo evaluation of 90Nb-labeled monoclonal antibody

    International Nuclear Information System (INIS)

    Radchenko, Valery

    2013-01-01

    Nuclear medicine is a modern and highly effective tool for the detection and treatment of oncological disease. Molecular imaging based on radiotracers includes single photon emission tomography (SPECT) and positron emission tomography (PET), which provide non-invasive tumor visualization on nano- and picomolar level, respectively. Currently, many novel tracers for more precise discovery of small tumors and metastases have been introduced and are under investigation. Many of them are protein-based biomolecules which nature herself produces as antigens for the eradication of tumor cells. Antibodies and antibody fragments play an important role in tumor diagnostics and treatment. PET imaging with antibodies and antibody fragments is called immuno-PET. The main issue that needs to be addressed is that appropriate radiotracers with half-lives related to the half-lives of biomolecules are needed. The development of novel radiotracers is a multistep, complicated task. This task includes the evaluation of production, separation and labeling strategy for chosen radionuclide. Finally, the biomolecule-radionuclide complex should be stable in time. An equally important factor is the economic suitability of the production strategy, which will lead to a key decision for future application of the developed radionuclide. In recent work, 90 Nb has been proposed as a potential candidate for application in immuno-PET. Its half-life of 14.6 hours is suitable for application with antibody fragments and some intact antibodies. 90 Nb has a relatively high positron branching of 53% and an optimal energy of β + emission of 0.35 MeV that can provide high quality of imaging with low dose of used radionuclide. First proof-of-principle studies have shown that 90 Nb: (i) can be produced in sufficient amount and purity by proton bombardment of natural zirconium target (ii) can be isolated from target material with appropriate radiochemical purity (iii) may be used for labeling of monoclonal

  13. Lung PET scan

    Science.gov (United States)

    ... Chest PET scan; Lung positron emission tomography; PET - chest; PET - lung; PET - tumor imaging; ... Grainger & Allison's Diagnostic Radiology: A Textbook of Medical Imaging . 6th ed. Philadelphia, ...

  14. Imaging of sigma receptors in tumors by PET with [C-11]SA4503

    International Nuclear Information System (INIS)

    Kawamura, K.; Kobayashi, T.; Oda, K.; Ishiwata, K.; Kubota, K.

    2002-01-01

    Aim: Sigma receptors are implicated in some diseases in the central nervous system (CNS), such as schizophrenia, depression, dementia and ischemia, and are also expressed in a variety of human tumors, such as melanoma, carcinoma of the breast, lung and prostate, and the brain tumor. Therefore, several radioligands have been proposed for imaging of sigma receptors by positron emission tomography (PET) and by single photon emission computed tomography. Recently, we have applied [C-11]labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ([C-11]SA4503) to mapping sigma1 receptors in the brain of monkeys and human. In the present study, we evaluated the potential of the [C-11]SA4503 PET for imaging of sigma receptors using the AH109A bearing rats, and the VX-2 carcinoma bearing rabbits. Materials and Methods: [C-11]SA4503 was injected i.v. into AH109A bearing rats, and the tissue distribution was measured by tissue dissection. To determine the receptor-specific uptake, cold SA4503 or haloperidol was co-injected into the other group of rats. The PET scanning were performed in the rats in the baseline condition and after pretreatment with haloperidol. In the VX-2 carcinoma bearing rabbits, PET scanning was also performed in the baseline and blockade conditions. The sigma receptors in the AH109A and VX-2 were measured in vitro by the standard membrane binding assays. Results: The sigma receptors were found in AH109A and VX-2. The density was much higher in VX-2 than in AH109A. In the tissue dissection study, the AH109A uptake of [C-11]SA4503 increased for 60 min after injection. By the co-injection of SA4503 or haloperidol, the AH109A uptake was enhanced. The PET study also confirmed that the radioactivity level in the AH109A was enhanced by the pretreatment with haloperidol. On the other hand, In the VX-2 carcinoma bearing rabbits, the radioactivity level of in VX-2 remained constant after initial uptake in the baseline PET measurement, but the VX-2 uptake was

  15. Synthesis and In Vitro and In Vivo Evaluation of a New 68Ga-Semicarbazone Complex: Potential PET Radiopharmaceutical for Tumor Imaging

    Directory of Open Access Journals (Sweden)

    N. S. Al-Hokbany

    2014-01-01

    Full Text Available In an attempt to develop new tumor imaging radiotracers with favorable biochemical properties, we have synthesized new 68Ga-2-acetylpyridine semicarbazone (68Ga-[APSC]2 as a potential positron emission tomography (PET tumor imaging agent using a straightforward and a one-step simple reaction. Radiochemical yield and purity were quantitative without HPLC purification. Biodistribution studies in nude mice model bearing human MDA-MB-231 cell line xenografts displayed significant tumor uptake of 68Ga-[APSC]2 radiotracer after 2 h postinjection (p.i.. The initial results demonstrate that 68Ga-[APSC]2 radiotracer may be useful probe for detecting and staging of hypoxic tumor using PET imaging modality.

  16. N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) potential δ-opioid receptor PET ligands

    International Nuclear Information System (INIS)

    Tyacke, Robin J.; Robinson, Emma S.J.; Schnabel, Rebecca; Lewis, John W.; Husbands, Stephen M.; Nutt, David J.; Hudson, Alan L.

    2002-01-01

    The properties of two prospective positron emission tomography (PET) ligands for the δ-opioid receptor, N1'-fluoroethyl-naltrindole (BU97001) and N1'-fluoroethyl-(14-formylamino)-naltrindole (BU97018) were investigated. Both were antagonists in the mouse vas deferens, and showed high affinity and selectivity, 1.81 nM and 3.09 nM respectively. [ 3 H]BU97001 binding to rat whole brain was also of high affinity, K D of 0.42 nM of and B MAX of 59.95 fmol mg of protein -1 . In autoradiographic studies, it was found to bind to brain areas previously shown to be associated with the δ-opioid receptor and good correlations were found to exist with naltrindole and DPDPE. BU97018 and especially BU97001 appear to show good potential as δ-opioid receptor PET ligands with the incorporation of 18 F

  17. Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Tetsuro Tago

    2018-01-01

    Full Text Available Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs, which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET. We summarize the results of radiosynthesis and biological evaluation of the HDAC ligands to identify their successful results and challenges. Since 2006, several small molecules that are radiolabeled with a radioisotope such as carbon-11 or fluorine-18 have been developed and evaluated using various assays including in vitro HDAC binding assays and PET imaging in rodents and non-human primates. Although most compounds do not readily cross the blood-brain barrier, adamantane-conjugated radioligands tend to show good brain uptake. Until now, only one HDAC radioligand has been tested clinically in a brain PET study. Further PET imaging studies to clarify age-related and disease-related changes in HDACs in disease models and humans will increase our understanding of the roles of HDACs in neurodegenerative diseases.

  18. Time-of-flight PET/CT using low-activity protocols: potential implications for cancer therapy monitoring

    International Nuclear Information System (INIS)

    Murray, Iain; Hasan, Syed; Quraishi, Shuaib; Avril, Norbert; Kalemis, Antonis; Glennon, Joe; Beyer, Thomas

    2010-01-01

    Accurate quantification of tumour tracer uptake is essential for therapy monitoring by sequential PET imaging. In this study we investigated to what extent a reduction in administered activity, synonymous with an overall reduction in repeated patient exposure, compromised the accuracy of quantitative measures using time-of-flight PET/CT. We evaluated the effect of reducing the emission count statistics, using a 64-channel GEMINI TF PET/CT system. Experiments were performed with the NEMA IEC body phantom at target-to-background ratios of 4:1 and 10:1. Emission data for 10 s, 30 s, 1 min, 2 min, 5 min and 30 min were acquired. Volumes of interest fitted to the CT outline of the spheres were used to calculate recovery coefficients for each target-to-background ratio and for different reconstruction algorithms. Whole-body time-of-flight PET/CT was performed in 20 patients 62±4 min after injection of 350±40 MBq (range 269-411 MBq) 18 F-FDG. From the acquired 2 min per bed position list mode data, simulated 1-min, 30-s and 15-s PET acquisitions were created. PET images were reconstructed using the TOF-OSEM algorithm and analysed for differences in SUV measurements resulting from the use of lower administered activity as simulated by reduced count statistics. In the phantom studies, overall we identified no significant quantitation bias over a wide range of acquired counts. With acquisition times as short as 10 s, lesions as small as 1 cm in diameter could still be identified. In the patient studies, visual analysis showed that emission scans as short as 15 s per bed position sufficiently identified tumour lesions for quantification. As the acquisition time per bed position decreased, the differences in SUV quantification of tumour lesions increased relative to the 2-min reference protocol. However, SUVs remained within the limits of reproducibility required for therapy monitoring. Measurements of SUVmean within the region of interest were less prone to noise than

  19. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Belinda A., E-mail: Belinda.Campbell@petermac.org [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Simoens, Nathalie [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Everitt, Sarah [Radiotherapy Services, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Burbury, Kate [Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

    2015-08-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

  20. Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

    International Nuclear Information System (INIS)

    Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

    2015-01-01

    Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required

  1. Alternative Radioligands for Investigating the Molecular Pharmacology of Melatonin Receptors.

    Science.gov (United States)

    Legros, Céline; Brasseur, Chantal; Delagrange, Philippe; Ducrot, Pierre; Nosjean, Olivier; Boutin, Jean A

    2016-03-01

    Melatonin exerts a variety of physiologic activities that are mainly relayed through the melatonin receptors MT1 and MT2 Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[(125)I]-iodomelatonin as a substitute for melatonin. We describe three iodinated ligands: 2-(2-[(2-iodo-4,5-dimethoxyphenyl)methyl]-4,5-dimethoxy phenyl) (DIV880) and (2-iodo-N-2-[5-methoxy-2-(naphthalen-1-yl)-1H-pyrrolo[3,2-b]pyridine-3-yl])acetamide (S70254), which are specific ligands at MT2 receptors, and N-[2-(5-methoxy-1H-indol-3-yl)ethyl]iodoacetamide (SD6), an analog of 2-[(125)I]-iodomelatonin with slightly different characteristics. Here, we further characterized these new ligands with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements, and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [(125)I]-S70254 is receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist [43% of melatonin on guanosine 5'-3-O-(thio)triphosphate binding assay], selective for MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissue samples. The molecular pharmacology of both human melatonin receptors MT1 and MT2, using a series of 24 ligands at these receptors and the new radioligands, did not lead to noticeable variations in the profiles. For the first time, we described radiolabeled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit better understanding of the role and implication in physiopathologic processes of the melatonin receptors. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Molecular imaging of {sigma} receptors: synthesis and evaluation of the potent {sigma}{sub 1} selective radioligand [{sup 18}F]fluspidine

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Steffen; Hiller, Achim; Deuther-Conrad, Winnie; Scheunemann, Matthias; Steinbach, Joerg; Brust, Peter [Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Research Site Leipzig, Interdisciplinary Isotope Research, Leipzig (Germany); Wiese, Christian; Grosse Maestrup, Eva; Schepmann, Dirk; Wuensch, Bernhard [Institut fuer Pharmazeutische und Medizinische Chemie der Westfaelischen Wilhelms-Universitaet Muenster, Muenster (Germany)

    2011-03-15

    Neuroimaging of {sigma}{sub 1} receptors in the human brain has been proposed for the investigation of the pathophysiology of neurodegenerative and psychiatric diseases. However, there is a lack of suitable {sup 18}F-labelled PET radioligands for that purpose. The selective {sigma}{sub 1} receptor ligand [{sup 18}F]fluspidine (1'-benzyl-3-(2-[{sup 18}F]fluoroethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]) was synthesized by nucleophilic {sup 18}F{sup -} substitution of the tosyl precursor. In vitro receptor binding affinity and selectivity were assessed by radioligand competition in tissue homogenate and autoradiographic approaches. In female CD-1 mice, in vivo properties of [{sup 18}F]fluspidine were evaluated by ex vivo brain section imaging and organ distribution of intravenously administered radiotracer. Target specificity was validated by organ distribution of [{sup 18}F]fluspidine after treatment with 1 mg/kg i.p. of the {sigma} receptor antagonist haloperidol or the emopamil binding protein (EBP) inhibitor tamoxifen. In vitro metabolic stability and in vivo metabolism were investigated by LC-MS{sup n} and radio-HPLC analysis. [{sup 18}F]Fluspidine was obtained with a radiochemical yield of 35-45%, a radiochemical purity of {>=} 99.6% and a specific activity of 150-350 GBq/{mu}mol (n = 6) within a total synthesis time of 90-120 min. In vitro, fluspidine bound specifically and with high affinity to {sigma}{sub 1} receptors (K{sub i} = 0.59 nM). In mice, [{sup 18}F]fluspidine rapidly accumulated in brain with uptake values of 3.9 and 4.7%ID/g and brain to blood ratios of 7 and 13 at 5 and 30 min after intravenous application of the radiotracer, respectively. By ex vivo autoradiography of brain slices, resemblance between binding site occupancy of [{sup 18}F]fluspidine and the expression of {sigma}{sub 1} receptors was shown. The radiotracer uptake in the brain as well as in peripheral {sigma}{sub 1} receptor expressing organs was significantly

  3. In vivo Evaluation of PEGylated 64Cu-liposomes with Theranostic and Radiotherapeutic Potential using Micro PET/CT

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager; Binderup, Tina

    2016-01-01

    The objective of this study was to evaluate the potentialof PEGylated 64Cu-liposomes in clinical diagnosticpositron emission tomography (PET) imaging andPEGylated 177Lu-liposomes in internal tumor radiotherapythrough in vivo characterization and dosimetric analysis in ahuman xenograft mouse model...

  4. In vivo imaging of neuro-inflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

    International Nuclear Information System (INIS)

    Chauveau, F.; Boutin, H.; Van Camp, N.; Thominiaux, C.; Dolle, F.; Tavitian, B.; Chauveau, F.; Boutin, H.; Van Camp, N.; Tavitian, B.; Hantraye, P.; Rivron, L.; Marguet, F.; Castel, M.N.; Rooney, T.; Benavides, J.; Chauveau, F.; Boutin, H.

    2011-01-01

    Purpose Neuro-inflammation is involved in neurological disorders through the activation of micro-glial cells. Imaging of neuro-inflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive bio-marker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N, N, 5- trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino[4, 5-b] indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuro-protective effects. Methods Here we report the radiolabelling of SSR180575 with 11 C and in vitro and in vivo imaging in an acute model of neuro-inflammation in rats. Results The image contrast and the binding of [ 11 C] SSR180575 are higher than that obtained with the isoquinoline- based TSPO radioligand, [ 11 C]PK11195. Competition studies demonstrate that [ 11 C]SSR180575 has high specific binding for the TSPO. Conclusion [ 11 C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuro-inflammation in animal models and in the clinic. (authors)

  5. Assessing brain immune activation in psychiatric disorders : Clinical and preclinical PET imaging studies of the 18-kDa translocator protein

    NARCIS (Netherlands)

    van der Doef, Thalia F; Doorduin, Janine; van Berckel, Bart N M; Cervenka, Simon

    2015-01-01

    Accumulating evidence from different lines of research suggests an involvement of the immune system in the pathophysiology of several psychiatric disorders. During recent years, a series of positron emission tomography (PET) studies have been published using radioligands for the translocator protein

  6. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement.

    Science.gov (United States)

    Sako, Takeo; Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky; Senda, Michio; Watanabe, Yasuyoshi

    2013-12-06

    Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Radioligand binding assay of cortisol using horse transcortin

    International Nuclear Information System (INIS)

    Dash, R.J.; Sharma, B.R.; Lata, V.

    1979-01-01

    A modified radioligand binding assay was developed to measure cortisol in a single methylene chloride extract of human plasma/serum. The assay utilises 5 percent horse serum for cortisol binding and 3 H-cortisol as tracer. Except for a cross reaction of 13.3 percent for cortisone and 7 percent for prednisolone that for other steroids tested was negligible. The assay sensitivity at the lower 95 percent inhibition of buffer controls was 20 pg/tube. The log dose logit response standard curve was linear between 80 pg and 5 ng/tube. Recovery(Y) of cortisol added (x) to male and pregnant female plasma was quantitated (y = 0.983 X-0.47, r = 0.98). Regression analysis of cortisol estimates obtained in 51 plasma/serum samples with this assay system and a specific radioimmunoassay (using cortisol-3-BSA antiserum) for plasma cortisol gave a coefficient of correlation (r) of 0.95 and a regression coefficient (b) of 0.97. The method was found to be simple and highly reproducible. Availability of all reagents in the aqueous phase permitted handling of a large number of samples by a single technician. (auth.)

  8. Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[{sup 18}f]fluorobenzoate

    Energy Technology Data Exchange (ETDEWEB)

    Jonson, Stephanie D.; Welch, Michael J. E-mail: welch@mirlink.wustl.edu

    1999-01-01

    Cholesteryl-p-[{sup 18}F]fluorobenzoate ([{sup 18}F]CFB) was investigated as a potential adrenal positron emission tomography (PET) imaging agent for the diagnostic imaging of adrenal disorders. We describe the synthesis, biodistribution, adrenal autoradiography, and baboon PET imaging of [{sup 18}F]CFB. The synthesis of [{sup 18}F]CFB was facilitated by the use of a specially designed microwave cavity that was instrumental in effecting 70-83% incorporation of fluorine-18 in 60 s via [{sup 18}F]fluoro-for-nitro exchange. Tissue distribution studies in mature female Sprague-Dawley rats showed good accumulation of [{sup 18}F]CFB in the steroid-secreting tissues, adrenals and ovaries, at 1 h postinjection. The effectiveness of [{sup 18}F]CFB to accumulate in diseased adrenals was shown through biodistribution studies in hypolipidemic rats, which showed a greater than threefold increase in adrenal uptake at 1 h and increased adrenal/liver and adrenal/kidney ratios. Analysis of the metabolites at 1 h in the blood, adrenals, spleen, and ovaries of hypolipidemic and control rats showed the intact tracer representing greater than 86%, 93%, 92%, and 82% of the accumulated activity, respectively. [{sup 18}F]CFB was confirmed to selectively accumulate in the adrenal cortex versus the adrenal medulla by autoradiography. Normal baboon PET imaging with [{sup 18}F]CFB effectively showed adrenal localization as early as 15 min after injection of the tracer, with enhanced adrenal contrast seen at 60-70 min. These results suggest that [{sup 18}F]CFB may be useful as an adrenal PET imaging agent for assessing adrenal disorders.

  9. Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

    Science.gov (United States)

    Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

    2012-06-01

    Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P measurements with acceptable radiation exposure. Although further modifications to improve the performance of (18)F-NOS are needed, these data show the feasibility of PET of iNOS in the heart and other tissues.

  10. Radiosynthesis and in vitro validation of 3H-NS14492 as a novel high affinity alpha7 nicotinic receptor radioligand

    DEFF Research Database (Denmark)

    Magnussen, Janus H.; Ettrup, Anders; Donat, Cornelius K.

    2015-01-01

    The neuronal alpha 7 nicotinic acetylcholine receptor is a homo-pentameric ligand-gated ion channel that is a promising drug target for cognitive deficits in Alzheimer's disease and schizophrenia. We have previously described 11C-NS14492 as a suitable agonist radioligand for in vivo positron...... emission tomography (PET) occupancy studies of the alpha 7 nicotinic receptor in the pig brain. In order to investigate the utility of the same compound for in vitro studies, 3H-NS14492 was synthesized and its binding properties were characterized using in vitro autoradiography and homogenate binding...... assays in pig frontal cortex. 3H-NS14492 showed specific binding to alpha 7 nicotinic receptors in autoradiography, revealing a dissociation constant (Kd) of 2.1 ± 0.7 nM and a maximum number of binding sites (Bmax) of 15.7±2.0 fmol/mg tissue equivalent. Binding distribution was similar...

  11. Synthesis and characterization in monkey of [{sup 11}C]SP203 as a radioligand for imaging brain metabotropic glutamate 5 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Simeon, Fabrice G.; Liow, Jeih-San; Zhang, Yi; Hong, Jinsoo; Gladding, Robert L.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD (United States)

    2012-12-15

    [{sup 18}F]SP203 (3-fluoro-5-(2-(2-([{sup 18}F]fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile) is an effective high-affinity and selective radioligand for imaging metabotropic 5 receptors (mGluR5) in human brain with PET. To provide a radioligand that may be used for more than one scanning session in the same subject in a single day, we set out to label SP203 with shorter-lived {sup 11}C (t{sub 1/2} = 20.4 min) and to characterize its behavior as a radioligand with PET in the monkey. Iodo and bromo precursors were obtained by cross-coupling 2-fluoromethyl-4-((trimethylsilyl)ethynyl)-1,3-thiazole with 3,5-diiodofluorobenzene and 3,5-dibromofluorobenzene, respectively. Treatment of either precursor with [{sup 11}C]cyanide ion rapidly gave [{sup 11}C]SP203, which was purified with high-performance liquid chromatography. PET was used to measure the uptake of radioactivity in brain regions after injecting [{sup 11}C]SP203 intravenously into rhesus monkeys at baseline and under conditions in which mGluR5 were blocked with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP). The emergence of radiometabolites in monkey blood in vitro and in vivo was assessed with radio-HPLC. The stability of [{sup 11}C]SP203 in human blood in vitro was also measured. The iodo precursor gave [{sup 11}C]SP203 in higher radiochemical yield (>98 %) than the bromo precursor (20-52 %). After intravenous administration of [{sup 11}C]SP203 into three rhesus monkeys, radioactivity peaked early in brain (average 12.5 min) with a regional distribution in rank order of expected mGluR5 density. Peak uptake was followed by a steady decline. No radioactivity accumulated in the skull. In monkeys pretreated with MTEP before [{sup 11}C]SP203 administration, radioactivity uptake in brain was again high but then declined more rapidly than in the baseline scan to a common low level. [{sup 11}C]SP203 was unstable in monkey blood in vitro and in vivo, and gave predominantly less lipophilic radiometabolites

  12. Comparison of 18F-FDG PET/MRI and MRI alone for whole-body staging and potential impact on therapeutic management of women with suspected recurrent pelvic cancer: a follow-up study.

    Science.gov (United States)

    Sawicki, Lino M; Kirchner, Julian; Grueneisen, Johannes; Ruhlmann, Verena; Aktas, Bahriye; Schaarschmidt, Benedikt M; Forsting, Michael; Herrmann, Ken; Antoch, Gerald; Umutlu, Lale

    2018-04-01

    To evaluate the diagnostic performance of 18 F-FDG PET/MRI for whole-body staging and potential changes in therapeutic management of women with suspected recurrent pelvic cancer in comparison with MRI alone. Seventy-one consecutive women (54 ± 13 years, range: 25-80 years) with suspected recurrence of cervical (32), ovarian (26), endometrial (7), vulvar (4), and vaginal (2) cancer underwent PET/MRI including a diagnostic contrast-enhanced MRI protocol. PET/MRI and MRI datasets were separately evaluated regarding lesion count, localization, categorization (benign/malignant), and diagnostic confidence (3-point scale; 1-3) by two physicians. The reference standard was based on histopathology results and follow-up imaging. Diagnostic accuracy and proportions of malignant and benign lesions rated correctly were retrospectively compared using McNemar's chi 2 test. Differences in diagnostic confidence were assessed by Wilcoxon test. Fifty-five patients showed cancer recurrence. PET/MRI correctly identified more patients with cancer recurrence than MRI alone (100% vs. 83.6%, p PET/MRI, MRI alone missed 4/15 patients with pelvic recurrence and miscategorized 8/40 patients with distant metastases as having local recurrence only. Based on the reference standard, 241 lesions were detected in the study cohort (181 malignant, 60 benign). While PET/MRI provided correct identification of 181/181 (100%) malignant lesions, MRI alone correctly identified 135/181 (74.6%) malignant lesions, which was significantly less compared to PET/MRI (p PET/MRI offered superior diagnostic accuracy (99.2% vs. 79.3%, p PET/MRI demonstrates excellent diagnostic performance and outperforms MRI alone for whole-body staging of women with suspected recurrent pelvic cancer, indicating potential changes in therapy management based on evaluation of local recurrence and distant metastatic spread.

  13. Potential role of 68Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease

    International Nuclear Information System (INIS)

    Prasad, Vikas; Brenner, Winfried; Tiling, Nikolaus; Ploeckinger, Ursula; Denecke, Timm

    2016-01-01

    Neuroendocrine tumours of the pancreas (pNET) are observed in 8 - 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 - 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, 68 Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of 68 Ga-DOTATOC PET/CT in screening of patients with vHLD. 68 Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on 68 Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV. Overall, 20 patients (8 men, 12 women; mean age 44.7 ± 11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. 68 Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9 ± 21.9 (range 5.0 - 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4 ± 8.3 mm (range 4 - 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 - 10.1). One patient presented with a solitary somatostatin receptor-positive lymph node metastasis. pNETs were

  14. Potential role of {sup 68}Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikas; Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Campus Virchow-Klinikum, Berlin (Germany); Tiling, Nikolaus; Ploeckinger, Ursula [Charite Universitaetsmedizin Berlin, Interdisziplinaeren Stoffwechsel-Centrum, Campus Virchow Klinikum, Berlin (Germany); Denecke, Timm [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-10-15

    Neuroendocrine tumours of the pancreas (pNET) are observed in 8 - 17 % of patients with von Hippel-Lindau disease (vHLD), and 11 - 20 % of these patients develop metastatic disease. MRI and CT have a very high resolution; however, their sensitivity and specificity for the detection of pNET amongst cystic lesions in the pancreas of vHLD patients are generally considered insufficient. In contrast, {sup 68}Ga-DOTATOC PET/CT demonstrates a high sensitivity for the diagnosis and staging of neuroendocrine tumours. In this study we investigated the potential role of {sup 68}Ga-DOTATOC PET/CT in screening of patients with vHLD. {sup 68}Ga-DOTATOC PET/three-phase contrast-enhanced CT was performed according to guidelines in all consecutive vHLD patients between January 2012 and November 2015. All patients underwent additional MRI imaging of the abdomen, spine, and head. Chromogranin A (CgA) was determined at the time of the PET/CT examination. A lesion seen on {sup 68}Ga-DOTATOC PET in the pancreas was defined as positive if the uptake was visually higher than in the surrounding tissues. Lesions were quantified using maximum SUV. Overall, 20 patients (8 men, 12 women; mean age 44.7 ± 11.1 years) were prospectively examined. Genetically, 12 patients had type 1 vHLD and 8 had type 2 vHLD. {sup 68}Ga-DOTATOC PET/CT detected more pNET than morphological imaging (CT or MRI): 11 patients (55 %; 8 type 1, 3 type 2) vs. 9 patients (45 %; 6 type 1, 3 type 2). The concentration of CgA was mildly elevated in 2 of 11 patients with pNET. The mean SUVmax of the pancreatic lesions was 18.9 ± 21.9 (range 5.0 - 65.6). Four patients (36.4 %) had multiple pNETs. The mean size of the lesions on CT and/or MRI was 10.4 ± 8.3 mm (range 4 - 38 mm), and 41.1 % were larger than 10 mm. In addition, somatostatin receptor-positive cerebellar and spinal haemangioblastomas were detected in three patients (SUVmax 2.1 - 10.1). One patient presented with a solitary somatostatin receptor-positive lymph

  15. In vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Waterhouse, Rikki N. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States) and Department of Radiology, Columbia University, New York, NY 10032 (United States) and Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)]. E-mail: rnw7@columbia.edu; Chang, Raymond C. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Zhao, Jun [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States); Carambot, Patty E. [Department of Psychiatry, Columbia University, New York, NY 10032 (United States); Neurobiology and Imaging Program, Department of Biological Psychiatry, New York State Psychiatric Institute, New York, NY 10032 (United States)

    2006-02-15

    Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K {sub D}=0.5{+-}0.2 nM, log P=2.9) sigma-1 receptor radiotracer [{sup 18}F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [{sup 18}F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [{sup 18}F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [{sup 18}F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([{sup 18}F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [{sup 18}F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([{sup 18}F]SFE) (K {sub D}=5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [{sup 18}F]SFE was synthesized (n=4) as previously described in good yield (54{+-}6% EOB), high specific activity (2.1{+-}0.6 Ci/{mu}mol EOS) and radiochemical purity (98{+-}1%) and evaluated in awake adult male rats. Results: Similar to [{sup 18}F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [{sup 18}F]SFE were highest in occipital cortex (1.86{+-}0.06 %ID/g) and frontal cortex (1.76{+-}0.38 %ID/g), and lowest in the hippocampus (1.01{+-}0.02%ID/g). Unlike [{sup 18}F]FPS, [{sup 18}F]SFE cleared from the brain with {approx}40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [{sup 18}F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [{sup 18}F]SFE in discrete brain regions. Conclusions

  16. In vivo evaluation in rats of [18F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine as a potential radiotracer for PET assessment of CNS sigma-1 receptors

    International Nuclear Information System (INIS)

    Waterhouse, Rikki N.; Chang, Raymond C.; Zhao, Jun; Carambot, Patty E.

    2006-01-01

    Introduction: Sigma-1 receptors are expressed throughout the mammalian central nervous system (CNS) and are implicated in several psychiatric disorders, including schizophrenia and depression. We have recently evaluated the high-affinity (K D =0.5±0.2 nM, log P=2.9) sigma-1 receptor radiotracer [ 18 F]1-(3-fluoropropyl)-4-(4-cyanophenoxymethyl)piperidine, [ 18 F]FPS, in humans. In contrast to appropriate kinetics exhibited in baboon brain, in the human CNS, [ 18 F]FPS does not reach pseudoequilibrium by 4 h, supporting the development of a lower-affinity tracer [Waterhouse RN, Nobler MS, Chang RC, Zhou Y, Morales O, Kuwabara H, et al. First evaluation of the sigma-1 receptor radioligand [ 18 F]1-3-fluoropropyl-4-((4-cyanophenoxy)-methyl)piperidine ([ 18 F]FPS) in healthy humans. Neuroreceptor Mapping 2004, July 15-18th, Vancouver, BC Canada 2004]. We describe herein the in vivo evaluation in rats of [ 18 F]1-(2-fluoroethyl)-4-[(4-cyanophenoxy)methyl]piperidine ([ 18 F]SFE) (K D =5 nM, log P=2.4), a structurally similar, lower-affinity sigma-1 receptor radioligand. Methods: [ 18 F]SFE was synthesized (n=4) as previously described in good yield (54±6% EOB), high specific activity (2.1±0.6 Ci/μmol EOS) and radiochemical purity (98±1%) and evaluated in awake adult male rats. Results: Similar to [ 18 F]FPS, regional brain radioactivity concentrations [percentage of injected dose per gram of tissue (%ID/g), 15 min] for [ 18 F]SFE were highest in occipital cortex (1.86±0.06 %ID/g) and frontal cortex (1.76±0.38 %ID/g), and lowest in the hippocampus (1.01±0.02%ID/g). Unlike [ 18 F]FPS, [ 18 F]SFE cleared from the brain with ∼40% reduction in peak activity over a 90-min period. Metabolite analysis (1 h) revealed that [ 18 F]SFE was largely intact in the brain. Blocking studies showed a large degree (>80%) of saturable binding for [ 18 F]SFE in discrete brain regions. Conclusions: We conclude that [ 18 F]SFE exhibits excellent characteristics in vivo and may provide

  17. [11C]-MeJDTic: a novel radioligand for κ-opioid receptor positron emission tomography imaging

    International Nuclear Information System (INIS)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome; Perrio, Cecile; Debruyne, Daniele; Barre, Louisa

    2008-01-01

    Introduction: Radiopharmaceuticals that can bind selectively the κ-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of κ-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the κ-opioid receptor in mice. Methods: [ 11 C]-MeJDTic was prepared by methylation of JDTic with [ 11 C]-methyl triflate. The binding of [ 11 C]-MeJDTic to κ-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [ 11 C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the κ receptor is largely expressed. [ 11 C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a κ referring agonist), morphine (a μ agonist) and naltrindole (a δ antagonist) demonstrated that this uptake was the result of specific binding to the κ-opioid receptor. Conclusion: These findings suggested that [ 11 C]-MeJDTic appeared to be a promising selective 'lead' radioligand for κ-opioid receptor PET imaging

  18. Inaccurate Assessment of Canine Body Condition Score, Bodyweight, and Pet Food Labels: A Potential Cause of Inaccurate Feeding

    Directory of Open Access Journals (Sweden)

    Philippa S. Yam

    2017-06-01

    Full Text Available The objectives were to investigate owners’ ability to assign the correct bodyweight (BW and body condition score (BCS to their dog and to interpret wet and dry pet food labels by estimating how much to feed daily. One hundred and seventy-four questionnaires were completed. Owner estimated BW was compared to actual BW, correct being defined within ±10% of actual BW. Correct interpretation of the total amount of food required was determined by the number of cans (±25% of cans required for wet food and grams (±20% of grams for dry food, based on the dog’s actual BW, the feeding guidelines on the label, and a comparison with the owner’s estimate. Eleven percent of owners overestimated BCS and 19% overestimated BW. Only 48% of owners could correctly estimate their dog’s BW. Only 23% and 43% of owners could correctly estimate how much wet and dry food to feed, respectively. Chi-square analysis demonstrated a significant positive association for owners correctly estimating their dog’s BW and interpreting the wet pet food label. Many owners are not aware of their pet’s BCS and BW and cannot accurately interpret pet food labels. Further owner education to improve these skills is needed if dogs are to be fed correctly.

  19. PET or PET-CT with cancer screening

    International Nuclear Information System (INIS)

    Wang Taisong; Zhao Jinhua; Song Jianhua

    2007-01-01

    At present, cancer screening remains a lot of debate in contemporary medical practice. Many constitutes have done a lot of experiments in cancer screening. The same version is that recommendations and decisions regarding cancer screening should be based on reliable data, not self- approbation. Now, some institutes advocate 18 F-FDG PET or 18 F-FDG PET-CT for cancer screening, here, discussed status quo, potential financial, radiation safety and statistical data in 18 F-FDG PET or 18 F-FDG PET- CT cancer screening. (authors)

  20. The potential of a modified physiologically equivalent temperature (mPET) based on local thermal comfort perception in hot and humid regions

    Science.gov (United States)

    Lin, Tzu-Ping; Yang, Shing-Ru; Chen, Yung-Chang; Matzarakis, Andreas

    2018-02-01

    Physiologically equivalent temperature (PET) is a thermal index that is widely used in the field of human biometeorology and urban bioclimate. However, it has several limitations, including its poor ability to predict thermo-physiological parameters and its weak response to both clothing insulation and humid conditions. A modified PET (mPET) was therefore developed to address these shortcomings. To determine whether the application of mPET in hot-humid regions is more appropriate than the PET, an analysis of a thermal comfort survey database, containing 2071 questionnaires collected from participants in hot-humid Taiwan, was conducted. The results indicate that the thermal comfort range is similar (26-30 °C) when the mPET and PET are applied as thermal indices to the database. The sensitivity test for vapor pressure and clothing insulation also show that the mPET responds well to the behavior and perceptions of local people in a subtropical climate.

  1. MicroPET imaging of 5-HT{sub 1A} receptors in rat brain: a test-retest [{sup 18}F]MPPF study

    Energy Technology Data Exchange (ETDEWEB)

    Aznavour, Nicolas [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[Laboratory of Neuroenergetics and Cellular Dynamics, EPFL, SV, BMI, Lausanne (Switzerland); Benkelfat, Chawki; Gravel, Paul [McGill University, Department of Psychiatry, Montreal, QC (Canada)]|[McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada); Aliaga, Antonio [McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Rosa-Neto, Pedro [Douglas Hospital, Molecular NeuroImaging Laboratory, Montreal, QC (Canada); Bedell, Barry [McGill University, Department of Neurology and Neurosurgery, Montreal, QC (Canada)]|[McGill University, Department of Small Animal Imaging Laboratory, Montreal, QC (Canada); Zimmer, Luc [CERMEP, ANIMAGE Department, Lyon (France)]|[Universite Lyon 1 and CNRS, Lyon (France); Descarries, Laurent [Universite de Montreal, Department of Pathology and Cell Biology, Montreal, QC (Canada)]|[Universite de Montreal, Department of Physiology, Montreal, QC (Canada)]|[Universite de Montreal, GRSNC, Montreal, QC (Canada)

    2009-01-15

    Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [{sup 18}F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptors in different regions of animal and human brain, including that of 5-HT{sub 1A} autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. MicroPET brain imaging of 5-HT{sub 1A} receptors with [{sup 18}F]MPPF thus represents a promising avenue for investigating 5-HT{sub 1A} receptor function in rat. (orig.)

  2. Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans

    International Nuclear Information System (INIS)

    Matusch, A.; Rota Kops, E.; Winz, O.H.; Elmenhorst, D.; Herzog, H.; Hurlemann, R.; Zilles, K.; Bauer, A.

    2007-01-01

    Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT 2A receptor (5-HT 2A R) radioligand [ 18 F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [ 18 F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 μg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes ±95 % CI of -1.0 ± 1.6 % and +4.1 ± 1.8 % versus -1.2 ± 2.6 %) in large cortical regions presenting high basal uptake of both, [ 18 F]altanserin and ketamine. Marginal decreases of 4 % of radioligand binding were observed in the frontal lobe, and 8 % in a posteriorly specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT2 AR which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [ 15 O]butanol PET. This may caused by accelerated clearance of unspecifically bound [ 18 F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [ 18 F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [ 18 F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of

  3. Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.

    Science.gov (United States)

    Chiotellis, Aristeidis; Mu, Linjing; Müller, Adrienne; Selivanova, Svetlana V; Keller, Claudia; Schibli, Roger; Krämer, Stefanie D; Ametamey, Simon M

    2013-01-01

    In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Use of [125I]-iodohistamine-labelled steroid derivatives as radioligands for radioimmunoassay of natural and synthetic steroids

    International Nuclear Information System (INIS)

    Stanczyk, F.Z.; Goebelsmann, U.

    1981-01-01

    [ 125 I]-Iodohistamine-labelled steroid derivatives were prepared and utilized as radioligands in radioimmunoassays of progesterone, testosterone, estradiol, estriol, estriol-16α-glucuronide, levonorgestrel, norethindrone and medroxyprogesterone acetate. The binding of these iodinated radioligands was compared to that of the corresponding tritiated steroids and their effect on the sensitivity and slope of standard curves was examined. The results demonstrate that much higher antibody dilutions could be used with iodinated than with tritiated radioligands. In general, standard curves obtained with iodinated radioligands were more sensitive than those obtained with tritiated steroids, but standard curves had steeper slopes when tritiated rather than iodinated radioligands were used. The data, summarizing our 5-year experience with steroid-[ 125 I]-iodohistamine derivatives, indicate that these tracers play an important role in radioimmunoassay systems for both natural and synthetic steroids. (author)

  5. CT-based texture analysis potentially provides prognostic information complementary to interim fdg-pet for patients with hodgkin's and aggressive non-hodgkin's lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Ganeshan, B.; Miles, K.A.; Shortman, R.; Afaq, A.; Ardeshna, K.M.; Groves, A.M.; Kayani, I. [University College London, Institute of Nuclear Medicine, London (United Kingdom); Babikir, S. [International Atomic Energy Agency (IAEA), Human Health Division, Nuclear Medicine and Diagnostic Imaging Section, Vienna (Austria)

    2017-03-15

    The purpose of this study was to investigate the ability of computed tomography texture analysis (CTTA) to provide additional prognostic information in patients with Hodgkin's lymphoma (HL) and high-grade non-Hodgkin's lymphoma (NHL). This retrospective, pilot-study approved by the IRB comprised 45 lymphoma patients undergoing routine 18F-FDG-PET-CT. Progression-free survival (PFS) was determined from clinical follow-up (mean-duration: 40 months; range: 10-62 months). Non-contrast-enhanced low-dose CT images were submitted to CTTA comprising image filtration to highlight features of different sizes followed by histogram-analysis using kurtosis. Prognostic value of CTTA was compared to PET FDG-uptake value, tumour-stage, tumour-bulk, lymphoma-type, treatment-regime, and interim FDG-PET (iPET) status using Kaplan-Meier analysis. Cox regression analysis determined the independence of significantly prognostic imaging and clinical features. A total of 27 patients had aggressive NHL and 18 had HL. Mean PFS was 48.5 months. There was no significant difference in pre-treatment CTTA between the lymphoma sub-types. Kaplan-Meier analysis found pre-treatment CTTA (medium feature scale, p=0.010) and iPET status (p<0.001) to be significant predictors of PFS. Cox analysis revealed that an interaction between pre-treatment CTTA and iPET status was the only independent predictor of PFS (HR: 25.5, 95% CI: 5.4-120, p<0.001). Specifically, pre-treatment CTTA risk stratified patients with negative iPET. CTTA can potentially provide prognostic information complementary to iPET for patients with HL and aggressive NHL. (orig.)

  6. Diagnostic potential of PET/CT using a {sup 68}Ga-labelled prostate-specific membrane antigen ligand in whole-body staging of renal cell carcinoma: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, Lino M.; Buchbender, Christian; Boos, Johannes; Antoch, Gerald [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Giessing, Markus [University Dusseldorf, Medical Faculty, Department of Urology, Dusseldorf (Germany); Ermert, Johannes [Juelich Research Center, Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Juelich (Germany); Antke, Christina; Hautzel, Hubertus [University Dusseldorf, Medical Faculty, Department of Nuclear Medicine, Dusseldorf (Germany)

    2017-01-15

    To evaluate the diagnostic potential of whole-body PET/CT using a {sup 68}Ga-labelled PSMA ligand in renal cell carcinoma (RCC). Six patients with histopathologically proven RCC underwent {sup 68}Ga-PSMA PET/CT. Each PET/CT scan was evaluated in relation to lesion count, location and dignity. SUVmax was measured in primary tumours and PET-positive metastases. Tumour-to-background SUVmax ratios (TBR{sub SUVmax}) were calculated for primary RCCs in relation to the surrounding normal renal parenchyma. Metastasis-to-background SUVmax ratios (MBR{sub SUVmax}) were calculated for PET-positive metastases in relation to gluteal muscle. Five primary RCCs and 16 metastases were evaluated. The mean SUVmax of the primary RCCs was 9.9 ± 9.2 (range 1.7 - 27.2). Due to high uptake in the surrounding renal parenchyma, the mean TBR{sub SUVmax} of the primary RCCs was only 0.2 ± 0.3 (range 0.02 - 0.7). Eight metastases showed focal {sup 68}Ga-PSMA uptake (SUVmax 9.9 ± 8.3, range 3.4 - 25.6). The mean MBR{sub SUVmax} of these PET-positive metastases was 11.7 ± 0.2 (range 4.4 - 28.1). All PET-negative metastases were subcentimetre lung metastases. {sup 68}Ga-PSMA PET/CT appears to be a promising method for detecting RCC metastases. However, no additional diagnostic value in assessing the primary tumour was found. (orig.)

  7. Effect of the prosthetic group on the pharmacologic properties of 18F-labeled rhodamine B, a potential myocardial perfusion agent for positron emission tomography (PET).

    Science.gov (United States)

    Bartholomä, Mark D; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H; Treves, S Ted; Packard, Alan B

    2012-12-27

    We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.

  8. The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

    Science.gov (United States)

    Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2013-01-01

    We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

  9. Uptake of 18F-DCFPyL in Paget's Disease of Bone, an Important Potential Pitfall in Clinical Interpretation of PSMA PET Studies.

    Science.gov (United States)

    Rowe, Steven P; Deville, Curtiland; Paller, Channing; Cho, Steve Y; Fishman, Elliot K; Pomper, Martin G; Ross, Ashley E; Gorin, Michael A

    2015-12-01

    Prostate-specific membrane antigen (PSMA)-targeted PET imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this image report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 18 F-DCFPyL, a small molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced CT, bone scan, and pelvic MRI consistent with Paget's disease of bone. The uptake of 18 F-DCFPyL in Paget's disease is most likely due to hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's, it is important for nuclear medicine physicians and radiologists interpreting PSMA PET/CT scans to be aware of the potential for this diagnostic pitfall. Correlation to findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis.

  10. Pet Health

    Science.gov (United States)

    ... companionship and a feeling of safety to your life. Before getting a pet, think carefully about which ... Gaining or losing a lot of weight quickly Strange behavior Being sluggish and tired Trouble getting up ...

  11. Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection

    International Nuclear Information System (INIS)

    Kumar, Vijay; Boddeti, Dilip K.; Evans, Scott G.; Roesch, Frank; Howman-Giles, Robert

    2011-01-01

    Introduction: 67 Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether 68 Ga-apo-transferrin ( 68 Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. Methods: An infection was induced in male Wistar rats by injecting 5x10 5 CFU units of Staphyococcus aureus in the right thigh muscle. 68 Ga-TF was synthesized by mixing 68 GaCl 3 with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 o C for 1 h. Animals were injected with 10-15 MBq of 68 Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. Results: When 68 Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. 68 GaCl 3 (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. Conclusion: The preliminary results suggest that 68 Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

  12. N-(n-benzylpiperidin-4-yl)-2-[18f]fluorobenzamide: a potential ligand for PET imaging of breast cancer

    International Nuclear Information System (INIS)

    Shiue, Chyng-Yann; Shiue, Grace G.; Benard, Francois; Visonneau, Sophie; Santoli, Daniela; Alavi, Abass A.

    2000-01-01

    N-(N-Benzylpiperidin-4-yl)-2-[ 18 F]fluorobenzamide (2), a potential ligand for PET imaging of sigma receptor, has been found to be a potential agent for detection of breast cancer. In vivo studies in severe combined immunodeficient (SCID) mice bearing MDA-MB231 tumors showed that the uptake of compound 2 in these tumors was high (3.8%/g); the ratios of tumor/muscle and tumor/blood were 6.2 and 7.0, respectively, at 1 h postinjection. Pretreatment of SCID mice with haldol increased the uptake of compound 2 in blood, muscle, and other well-perfused organs while decreasing its uptake in tumors. The ratios of tumor/muscle and tumor/blood decreased from 6.2 and 7.0 to 1.3 and 1.1, respectively, at 1 h postinjection. At 2 h postinjection, the ratios of tumor/muscle and tumor/blood decreased from 4.9 and 7.8 to 1.4 and 1.4, respectively. The tumor uptake of compound 2 in SCID mice bearing primary tumor explants from a human breast cancer patient was lower than that in MDA-MB231 tumors (1.66%/g versus 3.78%/g), and the ratios of tumor/muscle and tumor/blood were 3.5 and 3.7, respectively, at 1 h postinjection. These results suggest that compound 2 may be a potential ligand for PET imaging of breast cancer

  13. Novel PET sensors

    International Nuclear Information System (INIS)

    Cooper, C.R.

    2001-03-01

    This thesis describes the design, synthesis and evaluation of novel molecular sensors that utilize the phenomena of Photoinduced Electron Transfer (PET). PET design can be incorporated into molecules to allow them to selectively bind certain guest molecules. PET works by the modulation of electron potentials within a molecule. Binding events between a host and guest can, if designed suitably, change these potentials enough to cause a transfer of electronic charge within the molecular sensor. This event can be accurately and sensitively monitored by the use of ultra violet or fluorescence spectroscopy. A sensor molecule can be constructed by matching the guest to a suitable receptor site and incorporating this into a molecule containing a fluorophore with the correct electron potential characteristics. By using existing synthetic routes as well as exploiting new pathways these sensor molecules C n be constructed to contain a fluorophore separated from a guest receptor(s) by suitable spacers units. When put together these facets go to creating molecules that by design are sensitive and selective for certain guest molecules or functional groups. This methodology allows the synthetic chemist to rationally design and synthesise PET sensors, tailored to the needs of the guest. In this thesis the synthesis and evaluation of a novel PET sensors for D-glucosamine, disaccharides and fluoride is presented. It is believed that the novel sensors using the PET phenomenon presented in this thesis are a worthwhile extension of previous works undertaken by other groups around the world and shows new pathways to increasingly complex and sophisticated sensor molecular design. (author)

  14. Pet Allergy Quiz

    Science.gov (United States)

    ... Treatments ▸ Allergies ▸ Pet Allergy ▸ Pet Allergy Quiz Share | Pet Allergy Quiz More than half of U.S. households ... cat family. Yet, millions of people suffer from pet allergies. Take this quiz to test your knowledge ...

  15. β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [{sup 11}C]AZD2184

    Energy Technology Data Exchange (ETDEWEB)

    Mattsson, Patrik [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Forsberg, Anton; Halldin, Christer [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); Persson, Jonas; Nilsson, Lars-Goeran [Karolinska Institute and Stockholm University, Aging Research Center (ARC), Stockholm (Sweden); Nyberg, Lars [Umeaa University, Department of Radiation Sciences (Diagnostic Radiology), Umeaa (Sweden); Farde, Lars [Karolinska Institutet, Centre for Psychiatry Research, Department of Clinical Neuroscience, Stockholm (Sweden); AstraZeneca Translational Science Center at Karolinska Institutet, Stockholm (Sweden)

    2015-09-15

    Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [{sup 11}C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [{sup 11}C]AZD2184. The binding potential BP{sub ND} was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [{sup 11}C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP{sub ND} was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP{sub ND} were ApoE ε4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits. (orig.)

  16. β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [11C]AZD2184

    International Nuclear Information System (INIS)

    Mattsson, Patrik; Forsberg, Anton; Halldin, Christer; Persson, Jonas; Nilsson, Lars-Goeran; Nyberg, Lars; Farde, Lars

    2015-01-01

    Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [ 11 C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [ 11 C]AZD2184. The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region. The binding of [ 11 C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP ND were ApoE ε4 allele carriers. We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits. (orig.)

  17. Positron Emission Tomography (PET)

    International Nuclear Information System (INIS)

    Welch, M.J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs

  18. Positron Emission Tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs.

  19. Positron Emission Tomography (PET)

    Science.gov (United States)

    Welch, M. J.

    1990-01-01

    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

  20. Competitive advantage of PET/MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jadvar, Hossein, E-mail: jadvar@usc.edu; Colletti, Patrick M.

    2014-01-15

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved.

  1. Competitive advantage of PET/MRI.

    Science.gov (United States)

    Jadvar, Hossein; Colletti, Patrick M

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Competitive advantage of PET/MRI

    International Nuclear Information System (INIS)

    Jadvar, Hossein; Colletti, Patrick M.

    2014-01-01

    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved

  3. A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells

    International Nuclear Information System (INIS)

    Saeed, Muhammad; Tewson, Timothy J.; Erdahl, Colbin E.; Kohen, Amnon

    2012-01-01

    Introduction: Thymidylate synthase and folate receptors are well-developed targets of cancer therapy. Discovery of a simple and fast method for the conversion of 11 CH 3 Ito[ 11 C]-formaldehyde ( 11 CH 2 O) encouraged us to label the co-factor of this enzyme. Preliminary studies conducted on cell lines have demonstrated a preferential uptake of [11- 14 C]-(R)-N 5 ,N 10 -methylene-5,6,7,8-tetrahydrofolate ( 14 CH 2 H 4 folate) by cancerous cell vs. normal cells from the same organ (Saeed M., Sheff D. and Kohen A. Novel positron emission tomography tracer distinguishes normal from cancerous cells. J Biol Chem 2011;286:33872–33878), pointing out 11 CH 2 H 4 folate as a positron emission tomography (PET) tracer for cancer imaging. Herein we report the synthesis of 11 CH 2 H 4 folate, which may serve as a potential PET tracer. Methods: In a remotely controlled module, methyl iodide ( 11 CH 3 I) was bubbled into a reaction vial containing trimethylamine N-oxide in N,N-Dimethylformamide (DMF) and heated to 70°C for 2 min. Formaldehyde ( 11 CH 2 O) formed after the completion of reaction was then mixed with a solution of freshly prepared tetrahydrofolate (H 4 folate) by using a fast chemoenzymatic approach to accomplish synthesis of 11 CH 2 H 4 folate. Purification of the product was carried out by loading the crude reaction mixture on a SAX cartridge, washing with water to remove unbound impurities and finally eluting with a saline solution. Results: The synthesis and purification of 11 CH 2 H 4 folate were completed within 5 min. High-performance liquid chromatography analysis of the product after SAX purification indicates that more than 90% of the radioactivity that was retained on the SAX cartridge was in 11 CH 2 H 4 folate, with minor ( 11 CH 2 O. Conclusion: We present a fast (∼5 min) synthesis and purification of 11 CH 2 H 4 folate as a potential PET tracer. The final product is received in physiologically compatible buffer (100 mM sodium phosphate, pH 7

  4. Smoking-induced dopamine release studied with [{sup 11}C]Raclopride PET

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Cho, Sang Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Do Hoon [Center for Clinical Services, National Cancer Certer, Goyang (Korea, Republic of)] (and others)

    2005-10-15

    It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [{sup 11}C]raclopride. Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4 {+-} 1.7 years) were enrolled in this study. [{sup 1C}]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes (3 x 20s, 2 x 60s, 2 x 120s, 1 x 180s and 22 x 300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. The mean decrease in binding potential of [{sup 1C}]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, {rho} =0.4). These data demonstrate that in vivo imaging with [{sup 11}C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

  5. High non-specific binding of the {beta}{sub 1}-selective radioligand 2-{sup 125}I-ICI-H

    Energy Technology Data Exchange (ETDEWEB)

    Riemann, B. [Muenster Univ. (Germany). Department of Nuclear Medicine; Law, M.P. [Muenster Univ. (Germany). Department of Nuclear Medicine; Hammersmith Hospital, London (United Kingdom). MRC Clinical Sciences Centre; Kopka, K. [Muenster Univ. (DE). Department of Nuclear Medicine] [and others

    2003-08-01

    Aim: As results of cardiac biopsies suggest, myocardial {beta}{sub 1}-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac {beta}{sub 2}-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess {beta}-adrenoceptors non-invasively. Among the novel racemic analogues of the established {beta}{sub 1}-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to {beta}{sub 1}-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative subtype selective {beta}{sub 1}-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac {beta}-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-{sup 125}I-ICI-H from the silylated precursor 2-SiMe{sub 3}-ICI-H was established. The specific activity was 80 GBq/{mu}mol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high {beta}{sub 1}-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac {beta}-adrenoceptors. The radiolabelled counterpart 2-{sup 125}I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac {beta}{sub 1}-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-{sup 125}I-ICI-H is no suitable radiotracer for imaging in vivo. (orig.)

  6. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  7. Non-oncological positron emission tomography (PET): brain imaging; La tomographie par emission de positons (TEP) hors oncologie: l'exploration du cerveau

    Energy Technology Data Exchange (ETDEWEB)

    Lomena, F. [Centro de Diagnostico por la imagen (CDIC), Hospital Clinic, Servicio de medicina nuclear, Barcelona (Spain)

    2008-10-15

    Positron emission tomography (PET) allows evaluation of the central nervous system function. Imaging of regional cerebral blood flow and metabolism, and of several neurotransmission systems may be obtained using PET. PET quantification is accurate and has good test-retest reliability. For research purposes, PET has been used to study brain physiology, to explore neurological and psychiatric diseases pathophysiology and for the new drugs research and development. F.D.G. is the only PET radioligand with clinical application. Following criteria of evidence-based medicine, the clinical indications of F.D.G.-PET are: evaluation of treated gliomas, pre surgical study of partial refractory epilepsy and diagnosis of Alzheimer's disease when it is impossible to differentiate clinically from fronto-temporal dementia.

  8. Novel synthesis and initial preclinical evaluation of (18)F-[FDG] labeled rhodamine: a potential PET myocardial perfusion imaging agent.

    Science.gov (United States)

    AlJammaz, Ibrahim; Al-Otaibi, Basim; AlHindas, Hussein; Okarvi, Subhani M

    2015-10-01

    Myocardial perfusion imaging is one of the most commonly performed investigations in nuclear medicine studies. Due to the clinical importance of [(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) and its availability in almost every PET center, a new radiofluorinated [(18)F]-FDG-rhodamine conjugate was synthesized using [(18)F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [(18)F]-FDG-rhodamine conjugate was prepared in quantitative radiochemical yields, with total synthesis time of nearly 20 min and radiochemical purity of greater than 98%, without the need for HPLC purification, which make these approaches amenable for automation. Biodistribution studies in normal rats at 60 min post-injection demonstrated a high uptake in the heart (>11% ID/g) and favorable pharmacokinetics. Additionally, [(18)F]-FDG-rhodamine showed an extraction value of 27.63%±5.12% in rat hearts. These results demonstrate that [(18)F]-FDG-rhodamine conjugate may be useful as an imaging agent for the positron emission tomography evaluation of myocardial perfusion. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Development of N-substituted quinolinimides, as potential PET tracers for the visualisation of δ-opioid receptors

    International Nuclear Information System (INIS)

    Bourdier, Th.

    2005-12-01

    In order to develop radiotracers for in vivo studies of δ-opioid receptors by Positron Emission Tomography (PET) or Single Photon Emission computed Tomography (SPECT), we undertook the synthesis of halogenated analogues (chlorinated and brominated) of compound 12. These analogues were prepared by a convergent synthesis and from these novel structures a halogen exchange reaction has been performed to complete this series. These molecules were tested to determine their in vitro affinity and selectivity toward δ opioid receptors. The compounds 12 and 15 were labelled with carbon-11. The radiosynthesis of compound 12, in weak radioactivity chemistry, was performed first by the Stille reaction and second by a new methodology based on the transfer reaction of [ 11 C]-methyl group. This new methodology used a mono-organotin compound prepared by addition of [ 11 C]-iodomethane onto Lappert's stannylene. The compound [ 11 C]-12 was obtained with 60 and 10% radiochemical yield respectively. In order to produce higher radioactivity quantities, the Stille reaction was automated. The compounds [ 11 C]-12 and [ 11 C]-15 were obtained in 40 minutes with a specific radioactivity ranging from 322 to 747 mCi/μmol. (author)

  10. Comparison of {sup 18}F-FDG PET/MRI and MRI alone for whole-body staging and potential impact on therapeutic management of women with suspected recurrent pelvic cancer. A follow-up study

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, Lino M.; Kirchner, Julian; Schaarschmidt, Benedikt M.; Antoch, Gerald [University Dusseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Grueneisen, Johannes; Forsting, Michael; Umutlu, Lale [University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ruhlmann, Verena; Herrmann, Ken [University Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Aktas, Bahriye [University Duisburg-Essen, Medical Faculty, Department of Obstetrics and Gynecology, Essen (Germany)

    2018-04-15

    To evaluate the diagnostic performance of {sup 18}F-FDG PET/MRI for whole-body staging and potential changes in therapeutic management of women with suspected recurrent pelvic cancer in comparison with MRI alone. Seventy-one consecutive women (54 ± 13 years, range: 25-80 years) with suspected recurrence of cervical (32), ovarian (26), endometrial (7), vulvar (4), and vaginal (2) cancer underwent PET/MRI including a diagnostic contrast-enhanced MRI protocol. PET/MRI and MRI datasets were separately evaluated regarding lesion count, localization, categorization (benign/malignant), and diagnostic confidence (3-point scale; 1-3) by two physicians. The reference standard was based on histopathology results and follow-up imaging. Diagnostic accuracy and proportions of malignant and benign lesions rated correctly were retrospectively compared using McNemar's chi{sup 2} test. Differences in diagnostic confidence were assessed by Wilcoxon test. Fifty-five patients showed cancer recurrence. PET/MRI correctly identified more patients with cancer recurrence than MRI alone (100% vs. 83.6%, p < 0.01). In contrast to PET/MRI, MRI alone missed 4/15 patients with pelvic recurrence and miscategorized 8/40 patients with distant metastases as having local recurrence only. Based on the reference standard, 241 lesions were detected in the study cohort (181 malignant, 60 benign). While PET/MRI provided correct identification of 181/181 (100%) malignant lesions, MRI alone correctly identified 135/181 (74.6%) malignant lesions, which was significantly less compared to PET/MRI (p < 0.001). PET/MRI offered superior diagnostic accuracy (99.2% vs. 79.3%, p < 0.001) and diagnostic confidence in the categorization of malignant lesions compared with MRI alone (2.7 ± 0.5 vs. 2.4 ± 0.7, p < 0.001). PET/MRI demonstrates excellent diagnostic performance and outperforms MRI alone for whole-body staging of women with suspected recurrent pelvic cancer, indicating potential changes in therapy

  11. Carbon-11 labeled papaverine as a PET tracer for imaging PDE10A: radiosynthesis, in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Tu Zhude [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)], E-mail: tuz@mir.wustl.edu; Xu Jinbin; Jones, Lynne A.; Li Shihong; Mach, Robert H. [Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)

    2010-05-15

    Papaverine, 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline, a specific inhibitor of phosphodiesterase (PDE) 10A with IC{sub 50} values of 36 nM for PDE10A, 1,300 nM for PDE3A and 320 nM for PDE4D, has served as a useful pharmaceutical tool to study the physiological role of PDE10A. Here, we report the radiosynthesis of [{sup 11}C]papaverine and the in vitro and in vivo evaluation of [{sup 11}C]papaverine as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of papaverine with {sup 11}C was achieved by O-methylation of the corresponding des-methyl precursor with [{sup 11}C]methyl iodide. [{sup 11}C]papaverine was obtained with {approx}70% radiochemical yield and a specific activity >10 Ci/{mu}mol. In vitro autoradiography studies of rat and monkey brain sections revealed selective binding of [{sup 11}C]papaverine to PDE10A enriched regions: the striatum of rat brain and the caudate and putamen of rhesus monkey brain. The biodistribution of [{sup 11}C]papaverine in rats at 5 min demonstrated an initially higher accumulation in striatum than in other brain regions, however the washout was rapid. MicroPET imaging studies in rhesus macaques similarly displayed initial specific uptake in the striatum with very rapid clearance of [{sup 11}C]papaverine from brain. Our initial evaluation suggests that despite papaverine's utility for in vitro studies and as a pharmaceutical tool, [{sup 11}C]papaverine is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Analogs of papaverine having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

  12. Cross sectional PET study of cerebral adenosine A1 receptors in premanifest and manifest Huntington's disease

    International Nuclear Information System (INIS)

    Matusch, Andreas; Elmenhorst, David; Saft, Carsten; Kraus, Peter H.; Gold, Ralf; Hartung, Hans-Peter; Bauer, Andreas

    2014-01-01

    To study cerebral adenosine receptors (AR) in premanifest and manifest stages of Huntington's disease (HD). We quantified the cerebral binding potential (BP ND ) of the A 1 AR in carriers of the HD CAG trinucleotide repeat expansion using the radioligand [ 18 F]CPFPX and PET. Four groups were investigated: (i) premanifest individuals far (preHD-A; n = 7) or (ii) near (preHD-B; n = 6) to the predicted symptom onset, (iii) manifest HD patients (n = 8), and (iv) controls (n = 36). Cerebral A 1 AR values of preHD-A subjects were generally higher than those of controls (by up to 31 %, p 1 AR BP ND was observed to the levels of controls in preHD-B and undercutting controls in manifest HD by down to 25 %, p 1 AR BP ND and years to onset. Before onset of HD, the assumed annual rates of change of A 1 AR density were -1.2 % in the caudatus, -1.7 % in the thalamus and -3.4 % in the amygdala, while the corresponding volume losses amounted to 0.6 %, 0.1 % and 0.2 %, respectively. Adenosine receptors switch from supra to subnormal levels during phenoconversion of HD. This differential regulation may play a role in the pathophysiology of altered energy metabolism. (orig.)

  13. [{sup 11}C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zessin, Joerg [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)]. E-mail: j.zessin@fz-rossendorf.de; Deuther-Conrad, Winnie [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Kretzschmar, Marion [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Wuest, Frank [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Pawelke, Beate [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany); Brust, Peter [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Steinbach, Joerg [Institut fuer Interdisziplinaere Isotopenforschung, 04318 Leipzig (Germany); Bergmann, Ralf [Institut fuer Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf, 01314 Dresden (Germany)

    2006-01-15

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (S Me-Adam, 1) is a highly potent and selective inhibitor of the serotonin transporter (SPERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [{sup 11}C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [{sup 11}C]S Me-Adam. The radiochemical yield was 27{+-}5%, and the specific radioactivity was 26-40 GBq/{mu}mol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SPERT, such as the thalamus/hypothalamus region (3.59{+-}0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74{+-}0.95 at 60 min postinjection. The [{sup 11}C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38{+-}11% of the control value. Furthermore, no metabolites of [{sup 11}C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [{sup 11}C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

  14. [11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats

    International Nuclear Information System (INIS)

    Zessin, Joerg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wuest, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Joerg; Bergmann, Ralf

    2006-01-01

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (S Me-Adam, 1) is a highly potent and selective inhibitor of the serotonin transporter (SPERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [ 11 C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [ 11 C]S Me-Adam. The radiochemical yield was 27±5%, and the specific radioactivity was 26-40 GBq/μmol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SPERT, such as the thalamus/hypothalamus region (3.59±0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74±0.95 at 60 min postinjection. The [ 11 C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38±11% of the control value. Furthermore, no metabolites of [ 11 C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [ 11 C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain

  15. [11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats.

    Science.gov (United States)

    Zessin, Jörg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wüst, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Jörg; Bergmann, Ralf

    2006-01-01

    N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

  16. PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcelo A.; Schulthess, Gustav von; Veit-Haibach, Patrick [University Hospital Zurich, Department Medical Radiology, Nuclear Medicine, Zurich (Switzerland); University Hospital Zurich, Department Medical Radiology, Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Zurich (Switzerland); Kubik-Huch, Rahel A.; Freiwald-Chilla, Bianka [Kantonsspital Baden AG, Department of Radiology, Baden (Switzerland); Hauser, Nik [Kantonsspital Baden AG, Department of Gynaecology, Baden (Switzerland); Froehlich, Johannes M. [Guerbet AG, Zurich (Switzerland)

    2015-08-15

    To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. (orig.)

  17. Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936

    International Nuclear Information System (INIS)

    Risgaard, Rune; Ettrup, Anders; Balle, Thomas; Dyssegaard, Agnete; Hansen, Hanne Demant; Lehel, Szabolcs; Madsen, Jacob; Pedersen, Henrik; Püschl, Ask; Badolo, Lassina; Bang-Andersen, Benny; Knudsen, Gitte Moos; Kristensen, Jesper Langgaard

    2013-01-01

    Cerebral α 1 -adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α 1 -adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs targeting the α 1 -adrenoceptors. However, so far no suitable PET radioligand has been developed for brain imaging of α 1 -adrenoceptors. Here, we report the synthesis of both enantiomers of the desmethyl precursors of the high affinity α 1 -adrenoceptor ligand Lu AE43936 (). The two enantiomers of were subsequently [ 11 C] radiolabelled and evaluated for brain uptake and binding by PET imaging in Danish Landrace pigs. (S)-[ 11 C]- and (R)-[ 11 C]- showed very limited brain uptake. Pre-treatment with cyclosporine A (CsA) resulted in a large increase in brain uptake, indicating that (R)-[ 11 C]- is a substrate for active efflux-transporters. This was confirmed in Madin Darby canine kidney (MDCK) cells overexpressing permeability glycoprotein (Pgp). In conclusion, the limited brain uptake of both (S)-[ 11 C]- and (R)-[ 11 C]- in the pig brain necessitates the search for alternative radioligands for in vivo PET brain imaging of α 1 -adrenoceptors.

  18. Correction for Partial Volume Effect Is a Must, Not a Luxury, to Fully Exploit the Potential of Quantitative PET Imaging in Clinical Oncology

    DEFF Research Database (Denmark)

    Alavi, Abass; Werner, Thomas J; Høilund-Carlsen, Poul Flemming

    2018-01-01

    The partial volume effect (PVE) is considered as one of the major degrading factors impacting image quality and hampering the accuracy of quantitative PET imaging in clinical oncology. This effect is the consequence of the limited spatial resolution of whole-body PET scanners, which results in bl...

  19. Clinical Nononcologic Applications of PET/CT and PET/MRI in Musculoskeletal, Orthopedic, and Rheumatologic Imaging.

    Science.gov (United States)

    Gholamrezanezhad, Ali; Basques, Kyle; Batouli, Ali; Matcuk, George; Alavi, Abass; Jadvar, Hossein

    2018-06-01

    With improvements in PET/CT and PET/MRI over the last decade, as well as increased understanding of the pathophysiology of musculoskeletal diseases, there is an emerging potential for PET as a primary or complementary modality in the management of rheumatologic and orthopedic conditions. We discuss the role of PET/CT and PET/MRI in nononcologic musculoskeletal disorders, including inflammatory and infectious conditions and postoperative complications. There is great potential for an increased role for PET to serve as a primary or complementary modality in the management of orthopedic and rheumatologic disorders.

  20. Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

    Science.gov (United States)

    Shih, Jui-Hu; Ma, Kuo-Hsing; Chen, Chien-Fu F; Cheng, Cheng-Yi; Pao, Li-Heng; Weng, Shao-Ju; Huang, Yuahn-Sieh; Shiue, Chyng-Yann; Yeh, Ming-Kung; Li, I-Hsun

    2016-01-01

    The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  1. The Z-isomer of 11β-methoxy-17α-[123I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

    International Nuclear Information System (INIS)

    Rijks, Leonie J. M.; Boer, Gerard J.; Endert, Erik; Bruin, Kora de; Janssen, Anton G. M.; Royen, Eric A. van

    1997-01-01

    The potential of both stereoisomers of 11β-methoxy-17α-[ 123 I]iodovinylestradiol (E- and Z-[ 123 I]MIVE) as suitable radioligands for imaging of estrogen receptor(ER)-positive human breast tumours was studied. The 17α-[ 123 I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17α-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[ 123 I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[ 123 I]MIVE. The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake ratios were also highest for Z-[ 123 I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[ 123 I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[ 123 I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer

  2. Studies of Nicotinic Receptors in Non-human Primates Using PET and SPECT

    International Nuclear Information System (INIS)

    Kassiou, M.; University of Sydney,

    2002-01-01

    Full text: Observations of abnormalities in the densities of nicotinic acetylcholine receptors (nAChRs) in the brains of smokers and patients with various CNS disorders has suggested that noninvasive imaging and quantification of nAChRs using PET and SPECT would be useful. This offers further the understanding of the involvement of these receptors in these conditions as well as insight into their role in the normal functioning of the brain. As a prelude to human studies, newly developed PET and SPECT radioligands are first evaluated in animals to determine their suitability for clinical imaging. In the neurosciences the most widespread application of PET and SPECT in animal imaging has been in the study of non-human primates. The larger animals allow the performance of quantitative imaging to be achieved on conventional clinical human scanners. The use of non-human primates for imaging nAChRs in models of Parkinson's disease and smoking is described below. Nicotinic acetylcholine receptors have been implicated in PD's since it has been demonstrated postmortem that cortical nAChRs are reduced and parallel the increase in dementia that occurs in PD patients. In experimental animals it has shown that nicotine protects against MPTP-induced degeneration. MPTP degeneration representing the most widely used and validated animal model of PD. Also, a number of studies have indicated that smokers have a lower than expected incidence of PD, suggesting a protective effect of nicotine. In order to study nAChRs using PET we have developed [ 76 Br]bromoepibatidine. This work was carried out at the Service Hospitalier Frederic Joliot, Orsay France as part of the France-Australia collaboration. In papio papio baboon the brain uptake of [ 76 Br]bromoepibatidine was high with preferential localisation in the thalamus. The [ 76 Br]bromoepibatidine uptake is consistent with the known cerebral nAChR distribution in primates. The radioactivity in thalamus, striatum and cortices was

  3. Healthy Pets and People

    Science.gov (United States)

    ... prevent the spread of germs between pets and people. Keep pets and their supplies out of the kitchen, and ... a local wildlife rehabilitation facility. More Information Healthy Pets Healthy People Clean Hands Save Lives! Stay Healthy at Animal ...

  4. Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

    International Nuclear Information System (INIS)

    Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae

    2016-01-01

    This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV max and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV max were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV max was 4.7. In 16 patients who underwent follow-up PET/CT, SUV max was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment

  5. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Gao, Mingzhang; Wang, Min; Miller, Kathy D.; Zheng, Qi-Huang

    2012-01-01

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[ 11 C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [ 11 C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [ 11 C]CH 3 OTf through O-[ 11 C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [ 11 C]CO 2 , were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  6. Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes

    International Nuclear Information System (INIS)

    Wang Min; Wang Jiquan; Gao Mingzhang; Zheng Qihuang

    2008-01-01

    Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]8) and (3aR,9bS)-1-[ 11 C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5, 9b-hexahy dro-1H-benzo[g]indolium triflate ([ 11 C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [ 11 C]CH 3 OTf through N-[ 11 C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/μmol specific activity at EOB

  7. Radiochemical synthesis and biological evaluation of 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine as dopamine D{sub 4} receptor radioligand

    Energy Technology Data Exchange (ETDEWEB)

    Li, Gu-Cai; Zhang, Ru; Jiang, Kai-Jun; Chen, Bo [Hunan Institute of Engineering, Xiangtan (China). College of Chemistry and Chemical Engineering

    2014-09-01

    A potential dopamine D{sub 4} receptor radioligand, 3-[4-(4-[{sup 18}F]fluorobenzyl)piperazin-1-ylmethyl]pyrazolo[1,5-a]pyridine was synthesized through a one-pot two-step procedure with total yield 18.5% (decay corrected). The molar radioactivity was 115 GBq/μmol and the radiochemical purity was greater than 95.5%. Its affinity and selectivity for dopamine D{sub 2}-like receptors were measured through in vitro receptor binding experiments and the K{sub i} for D{sub 4} receptor was determined to be 17 ± 0.5 nM. The partition coefficient (Log P) of it was determined to be 2.80 ± 0.10 through octanol experiment. The in vivo biodistribution of it in rat brain exposed that the radioligand penetrates through blood-brain- barrier (BBB) and may specifically bind to dopamine D{sub 4} receptor. The results indicated that the radioligand shows promise for the in vivo study of dopamine D{sub 4} receptor. (orig.)

  8. Clinically unrecognized pulmonary aspiration during gastrointestinal endoscopy with sedation: A potential pitfall interfering the performance of 18F-FDG PET for cancer screening

    International Nuclear Information System (INIS)

    Hsieh, Te-Chun; Wu, Yu-Chin; Ding, Hueisch-Jy; Wang, Chih-Hsiu; Yen, Kuo-Yang; Sun, Shung-Shung; Yeh, Jun-Jun; Kao, Chia-Hung

    2011-01-01

    Purpose: We found several cases with unexpected pulmonary abnormalities on the 18 F-FDG PET scan after the gastrointestinal endoscopy with sedation during a compact health check-up course, interfering the interpretations of 18 F-FDG PET scan for cancer screening. The current studies aimed to analyze the incidence and the clinical relevance of this pulmonary finding. Materials and methods: From June to December 2009, 127 subjects undergoing the sequential gastrointestinal endoscopy with sedation and 18 F-FDG PET scan within 48 h as part of routine health check-up were retrospectively enrolled in this study. The incidence of abnormal pulmonary findings and their SUV max of FDG were calculated and correlated with the clinical manifestations. Results: Five subjects had abnormal 18 F-FDG PET findings but pulmonary symptoms were only found in 2. The SUV max did not seem to reflect the severity of pulmonary symptoms or the need of intervention. Although the incidence of unrecognized pulmonary aspiration featuring inflammation detected by the 18 F-FDG PET scan was high (3.94%, 5/127), the incidence of events needed intervention remained low (0.79%, 1/127), similar to those previously reported literatures. Conclusions: Although higher incidence of pulmonary aspiration in this study, it probably reflects the better sensitivity of 18 F-FDG PET for inflammation. The low incidence of clinical events needed intervention may still reflect the safety of sedation used for gastrointestinal endoscopy. Proper arrangement of the sequential examinations if subjects need both gastrointestinal endoscopy with sedation and 18 F-FDG PET is important to reduce the interference degrading the performance of 18 F-FDG PET in cancer screening, diagnosis or staging.

  9. Influence of scanning time window on the binding potentials of dopamine transporter in the brain of healthy volunteers with 11C-CFT PET imaging

    International Nuclear Information System (INIS)

    Qiu Chun; Zuo Chuantao; Zhang Zhengwei; Wu Ping; Zhang Huiwei; Guan Yihui

    2013-01-01

    Objective: To find the optimal scanning time window and then set up the normal binding potentials (BPs) of 2β-carbomethoxy-3β-(4-fluorophenyl)-(N- 11 C-methyl) tropane ( 11 C-CFT) DAT PET/CT imaging. Methods: Thirty-one healthy volunteers (20 males, 11 females, average age: (55.7±2.3) years), who all gave written informed consent, were divided into three age and gender-matched groups according to block randomization. Each group underwent static PET/CT scan in different time windows from 40-60 min, 60-80 min to 80-100 min after 11 C-CFT injection. To determine the best scanning time window, the ratios of caudate and putamen of all volunteers were analyzed using automatic ROI method (caudate (putamen)/parieto-occipital cotex-1) and compared by one-way analysis of variance and the least significant difference (LSD) t test. The ratio of the same area between different age-groups and gender-groups was compared with independent two-sample t test. Results: Ratios of left caudate (2.08±0.06, 1.75±0.07 and 1.77±0.12 respectively), right anterior putamen (2.33±0.06, 1.95±0.09 and 2.08±0.12 respectively) and bilateral posterior putamen (left: 1.88±0.66, 1.55±0.88 and 1.72±0.09; right: 1.98±0.07, 1.61±0.09 and 1.69±0.12) were all different in three time windows (F=3.588, 3.345, 4.479, 3.557, all P<0.05). There were significant differences in ratios of left caudate, right anterior and bilateral posterior putamen between 40-60 min and the 60-80 min (all P<0.05), as well as the ratios of left caudate between 40-60 min and the 80-100 min group (P<0.05). While no valid differences in ratios of those areas were shown between the groups of 60-80 min and 80-100 min scanning time window (all P>0.05). DAT densities in right and left side of caudate, anterior and posterior putamen were significantly lower in the group over 60 years of age than those under 60 years (t=-3.260, -3.090, -3.270, -3.190, -2.270, -3.110, all P<0.05), but were not different between gender

  10. Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET.

    Science.gov (United States)

    Vanicek, Thomas; Kutzelnigg, Alexandra; Philippe, Cecile; Sigurdardottir, Helen L; James, Gregory M; Hahn, Andreas; Kranz, Georg S; Höflich, Anna; Kautzky, Alexander; Traub-Weidinger, Tatjana; Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus; Kasper, Siegfried; Lanzenberger, Rupert

    2017-02-01

    Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BP ND ) in patients with ADHD and to assess associations of SERT BP ND between the brain regions. 25 medication-free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [ 11 C]DASB. SERT BP ND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BP ND of the investigated ROIs (P < 0.05; Bonferroni corrected). When correlating SERT BP ND and age in the ADHD and the healthy control group, we confirmed an age-related decline in brain SERT binding in the thalamus and insula (R 2  = 0.284, R 2  = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792-802, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

  11. [carbonyl-11C]Desmethyl-WAY-100635 (DWAY) is a potent and selective radioligand for central 5-HT1A receptors in vitro and in vivo

    International Nuclear Information System (INIS)

    Pike, V.W.; McCarron, J.A.; Hirani, E.; Hume, S.P.; Osman, S.; Poole, K.G.; Wikstroem, H.; Mensonidas, M.

    1998-01-01

    post mortem human brain cryosections after incubation with DWAY successfully delineated 5-HT 1A receptor distribution. Receptor-specific binding was eliminated in the presence of the selective 5-HT 1A receptor agonist, 8-OH-DPAT [(±)-8-hydroxy-2-dipropylaminotetralin]. (orig./MG) 5-HT 1A receptors in rat and monkey in vivo and for human brain in vitro, and (c) the metabolism and kinetics of DWAY appear favourable to successful biomathematical modelling of acquired PET data. Thus, DWAY warrants further evaluation as a radioligand for PET studies of 5-HT 1A receptors in human brain. (orig.)

  12. The translocator protein radioligand 18F-DPA-714 monitors antitumor effect of erufosine in a rat 9L intracranial glioma model

    International Nuclear Information System (INIS)

    Awde, Ali R.; Boisgard, Raphael; Theze, Benoit; Dubois, Albertine; Zheng, Jinzi; Winkeler, Alexandra; Dolle, Frederic; Jacobs, Andreas H.; Tavitian, Bertrand

    2013-01-01

    On the one hand, the translocator protein (TSPO) radioligand N,N-diethyl-2-(2-(4-(2- 18 F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ( 18 F-DPA-714) has been suggested to serve as an alternative radiotracer to image human glioma, and on the other hand the alkyl-phosphocholine erufosine (ErPC3) has been reported to induce apoptosis in otherwise highly apoptosis resistant glioma cell lines. The induction of apoptosis by ErPC3 requires TSPO, a mitochondrial membrane protein highly expressed in malignant gliomas. In this preclinical study, we monitored the effect of ErPC3 treatment in vivo using 18 F-DPA-714 PET. Methods: In vitro studies investigated the antitumor effect of ErPC3 in 9L rat gliosarcoma cells. In vivo, glioma-bearing rats were imaged with 18 F-DPA-714 for the time of treatment. Results: A significant decrease in 9L cell proliferation and viability and a significant increase in apoptosis and caspase-3 activation were demonstrated on ErPC3 treatment in cell culture. In the rat model, ErPC3 administration resulted in significant changes in 18 F-DPA-714 tumor uptake over the course of the treatment. Immunohistochemistry revealed reduced tumor volume and increased cell death in ErPC3-treated animals accompanied by infiltration of the tumor core by CD11b-positive micro-glia/macrophages and glial fibrillary acidic protein-positive astrocytes. Conclusion: Our findings demonstrate a potent antitumor effect of ErPC3 in vitro, in vivo, and ex vivo. PET imaging of TSPO expression using 18 F-DPA-714 allows effective monitoring and quantification of disease progression and response to ErPC3 therapy in intracranial 9L gliomas. (authors)

  13. Dynamic observation by PET in epilepsy

    International Nuclear Information System (INIS)

    Shimizu, Hiroyuki; Ishijima, Buichi; Iio, Masaaki.

    1990-01-01

    Before the era when positron emission tomography (PET) has emerged, much controversy has existed concerning regional cerebral blood flow in partial epilepsy. In 1979, PET revealed that cerebral blood flow is decreased during the interictal period, but is remarkably increased in the intraictal phase. In this paper, historical process of dynamic observation in epilepsy is reviewed. Potential use and limitations of PET in the clinical setting are discussed in view of the scanning methods and the relationships between PET and electroencephalograms, magnetic resonance imaging, and surgical treatment. (N.K.) 106 refs

  14. A potential role for the midbrain in integrating fat-free mass determined energy needs: An H2 (15) O PET study.

    Science.gov (United States)

    Weise, Christopher M; Thiyyagura, Pradeep; Reiman, Eric M; Chen, Kewei; Krakoff, Jonathan

    2015-06-01

    Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n = 64, 21F/43M; age 31.3 ± 9.1y; percentage of body fat [PFAT] 25.6 ± 10.7%; BMI 30.4 ± 9) underwent a 36h fast and subsequent H(2) (15) O positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. © 2015 Wiley Periodicals, Inc.

  15. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  16. Receiver operating characteristic analysis and its potential role in evaluating the effect of head movement in PET of the brain

    International Nuclear Information System (INIS)

    Patterson, H.; Clarke, G.H.; Lombardo, P.; McKay, W.J.; Austin and Repatriation Medical Centre, Heidelberg, VIC

    1999-01-01

    Full text: We outline an example of receiver operating characteristic (ROC) analysis in the assessment of image quality. ROC analysis is a measure of image quality that accounts for the consequences of the decision and the role of the observer. Kim and Haynie (Nuclear Diagnostic Imaging: Practical Clinical Applications. Melbourne: Macmillan, 1987) describe ROC analysis as an 'objective approach to the evaluation of diagnostic decision making'. ROC analysis is an ideal technique for evaluating images of a Hoffman brain phantom obtained using positron emission tomography. Images have been acquired with the phantom in different positions. The position of the phantom and the time the phantom remained in each position was based on the measurements of head movement during simulated brain imaging (Patterson et al., Technologists Symposium, ANZSNM, 1998). This study was undertaken to explore the potential of ROC analysis in determining the effect of movement on the ability to detect lesions of various sizes

  17. Pet Problems at Home: Pet Problems in the Community.

    Science.gov (United States)

    Soltow, Willow

    1984-01-01

    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  18. Quantitative imaging of protein targets in the human brain with PET

    International Nuclear Information System (INIS)

    Gunn, Roger N; Slifstein, Mark; Searle, Graham E; Price, Julie C

    2015-01-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  19. Quantitative imaging of protein targets in the human brain with PET

    Science.gov (United States)

    Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

    2015-11-01

    PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts

  20. Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT

    DEFF Research Database (Denmark)

    Ziebell, Morten

    a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding......Imaging of the dopamine transporter (DAT) with Single Photon Emission Computer Tomography (SPECT) has increasingly been used as a biomarker for the integrity of presynaptic dopaminergic nerve cells in patients with movement disorders. 123-I-labelled N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4...... potential of DAT. Finally the in vivo SERT binding in DAT images obtained with [123I]FP-CIT was significant as compared to the [123I]PE2I image. [123I]PE2I is a super selective SPECT DAT radioligand with optimal kinetic properties for accurate quantification of the DAT availability in striatum. Apart from...

  1. Evaluation of the superselective radioligand [123I]PE2I for imaging of the dopamine transporter in SPECT

    DEFF Research Database (Denmark)

    Ziebell, Morten

    2011-01-01

    a B/I ratio of [123I]PE2I. This B/I ratio (2.7h) gave rise to steady state conditions and excellent reproducibility. Further, manual delineation of ROI directly on SPECT images performed equally well to a MRI-defined probability map based ROI delineation in terms of intrasubject variability of binding......Imaging of the dopamine transporter (DAT) with Single Photon Emission Computer Tomography (SPECT) has increasingly been used as a biomarker for the integrity of presynaptic dopaminergic nerve cells in patients with movement disorders. 123-I-labelled N-(3-iodoprop-2E-enyl)-2-ß-carbomethoxy-3ß-(4...... potential of DAT. Finally the in vivo SERT binding in DAT images obtained with [123I]FP-CIT was significant as compared to the [123I]PE2I image. [123I]PE2I is a super selective SPECT DAT radioligand with optimal kinetic properties for accurate quantification of the DAT availability in striatum. Apart from...

  2. Histamine type I (H1) receptor radioligand binding studies on normal T cell subsets, B cells, and monocytes

    International Nuclear Information System (INIS)

    Cameron, W.; Doyle, K.; Rocklin, R.E.

    1986-01-01

    A single, specific binding site for [ 3 H]pyrilamine on normal human T helper, T suppressor, B cells, and monocytes was documented. The binding of the radioligand to its receptor is reversible with cold H 1 antagonist, saturates at 40 to 60 nM, and binding equilibrium is achieved in 2 to 4 min. Using a computer program (Ligand), the authors calculated the dissociation constants, binding capacities, and numbers of receptors per cell for each of the different cell types. Monocytes were found to have the highest affinity for [ 3 H]pyrilamine, followed by T helper cells, B cells and T suppressor cells (K/sub D/ = 44.6 +/- 49.4 nM). T suppressor cells were found to express the higher number of H 1 receptors per cell followed by B cells, T helper cells, and monocytes. The binding affinity for [ 3 H]pyrilamine increased over a 48-hr period, whereas the number of receptors per T cell was essentially unchanged. In contrast, T cells stimulated with Con A or PHA were shown to have a greater than fourfold increase in the number of receptors per cell, whereas the binding affinity for [ 3 H]pyrilamine decreased over the 48-hr period. Although the function of H 1 receptors on T cells, B cells, and monocytes has not been completely defined, this receptor has the potential of playing an important role in the modulating the immune response

  3. Quantitative PET of liver functions.

    Science.gov (United States)

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

  4. Quantitative PET of liver functions

    Science.gov (United States)

    Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

    2018-01-01

    Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

  5. Indeterminate findings on oncologic PET/CT: What difference dose PET/MRI make?

    Energy Technology Data Exchange (ETDEWEB)

    Fraum, Tyler J.; Fowler, Kathryn J.; McConathy, Jonathan; Dehdashti, Farokh [Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis (United States)

    2016-12-15

    Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies. A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16 %) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies. In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases

  6. Indeterminate findings on oncologic PET/CT: What difference dose PET/MRI make?

    International Nuclear Information System (INIS)

    Fraum, Tyler J.; Fowler, Kathryn J.; McConathy, Jonathan; Dehdashti, Farokh

    2016-01-01

    Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-["1"8F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies. A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16 %) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies. In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases, the

  7. Occurrence of imidacloprid, carbendazim, and other biocides in Italian house dust: Potential relevance for intakes in children and pets.

    Science.gov (United States)

    Salis, Severyn; Testa, Cecilia; Roncada, Paola; Armorini, Sara; Rubattu, Nicola; Ferrari, Angelo; Miniero, Roberto; Brambilla, Gianfranco

    2017-09-02

    The occurrence of pesticides intended for non-agricultural use was investigated in 206 dust samples drawn from vacuum-cleaner bags from residential flats in Italy. The multi-residue analysis targeted on 95 different active principles was performed with UPLC-MS/MS, with a Limit of Quantification (LOQ) of 0.008 μg/g dry weight. The results indicated the presence of imidacloprid (IMI) and carbendazim (CARB) in 30% and 26% of the samples, with a mean and P95 concentration between 1.6 and 39 and between 0.08 and 4.9 μg/g, respectively. Combined presence of two biocides was noted in 19.4% samples, of three biocides in 9.2% samples, of four biocides in 3.4% samples, and of five and six biocides in 0.5% and 1% samples, respectively. According to the estimated dust intake in infants/toddlers aged 6-24 months (16-100 mg d -1 ) and cats (200 mg d -1 ), it was possible to obtain risk characterization with respect to the Acceptable Daily Intake (ADI) for IMI of 0.060 mg/kg body weight (bw) proposed by the European Food Safety Authority (EFSA) and the chronic Population Adjusted Dose (cPAD) of 0.019 mg/kg bw d -1 by US-EPA. Under the worst-case scenario, the presence of IMI in dust indicates potential exceedance of the cPAD in kittens, to be considered as sentinel also accounting for combined exposure. This study highlights the relevance of consumer empowerment about the responsible use of pesticides as biocidal products in indoor environment.

  8. Facile synthesis of carbon-11-labeled arylpiperazinylthioalkyl derivatives as new PET radioligands for imaging of 5-HT1AR

    International Nuclear Information System (INIS)

    Gao Mingzhang; Wang Min; Zheng Qihuang

    2012-01-01

    Carbon-11-labeled arylpiperazinylthioalkyl derivatives, 2-((4-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)butyl)thio)benzo[d]oxazole ([ 11 C]5a), 2-((4-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)butyl)thio)-5,7-dimethylbenzo [d]oxazole ([ 11 C]5c), 2-((4-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)butyl)thio)benzo[d]thiazole ([ 11 C]5e), 2-((6-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)hexyl)thio)benzo[d]oxazole ([ 11 C]5g), 2-((6-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)hexyl)thio)-5,7-dimethylbenzo [d]oxazole ([ 11 C]5i), and 2-((6-(4-(2-[ 11 C]methoxyphenyl)piperazin-1-yl)hexyl)thio)benzo[d]thiazole ([ 11 C]5k), were prepared from their corresponding phenol precursors with [ 11 C]CH 3 OTf through O-[ 11 C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a Sep-Pak Plus C18 cartridge in 50–60% (n=5) radiochemical yields based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5±92.5 GBq/μmol (n=5). - Highlights: ► New arylpiperazinylthioalkyl derivatives were synthesized. ► New carbon-11-labeled arylpiperazinylthioalkyl derivatives were synthesized. ► Simplified solid-phase extraction (SPE) method was employed in radiosynthesis.

  9. Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

    International Nuclear Information System (INIS)

    Dolle, F.; Hinnen, F.; Damont, A.; Kuhnast, B.; Tavitian, B.; Fookes, C.; Pham, T.; Katsifis, A.; Tavitian, B.

    2008-01-01

    PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[ 18 F]F-Kryptofix 222 and 6.8-7.6 μ mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [ 18 F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/μ mol (2-4 Ci/μ mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [ 18 F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). (authors)

  10. Radiosynthesis of F-18 PBR111, a selective radioligand for imaging the translocator protein (18 kDa) with PET

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Hinnen, F.; Damont, A.; Kuhnast, B.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Inst Imagerie Biomed, LIME, F-91406 Orsay (France); Fookes, C.; Pham, T.; Katsifis, A. [Australian Nucl Sci and Technol Org, RRI, Lucas Heights, NSW 2234 (Australia); Tavitian, B. [INSERM, U803, F-91406 Orsay (France)

    2008-07-01

    PBR111 (2-(6-chloro-2-(4-(3-fluoro-propoxy)phenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-diethylacetamide) is a novel, reported, high-affinity and selective ligand for the translocator protein (18 kDa). PBR111 has been labelled with fluorine-18 (half-life: 109.8 min) using our Zymate-XP robotic system. The process involves (A) a simple one-step to syloxy-for-fluorine nucleophilic aliphatic substitution (performed at 165 degrees C for 5 min in DMSO using K[{sup 18}F]F-Kryptofix 222 and 6.8-7.6 {mu} mol of the corresponding tosylate as precursor for labelling) followed by (B) C-18 PrepSep cartridge pre-purification and(C) semi-preparative HPLC purification on a Waters Symmetry C-18. Up to 4.8 GBq (130 mCi) of [{sup 18}F]PBR111 could be obtained with specific radioactivities ranging from 74 to 148 GBq/{mu} mol (2-4 Ci/{mu} mol) in 75-80 min (HPLC purification and SepPak-based formulation included), starting from a 37.0 GBq (1.0 Ci) [{sup 18}F]fluoride batch. Overall non-decay-corrected isolated yields were 8-13% (13-21% decay-corrected). (authors)

  11. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M

    2015-01-01

    ]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs...

  12. Synthesis of carbon-11-labeled 5-HT6R antagonists as new candidate PET radioligands for imaging of Alzheimer's disease.

    Science.gov (United States)

    Wang, Xiaohong; Dong, Fugui; Miao, Caihong; Li, Wei; Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang; Xu, Zhidong

    2018-06-01

    Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT 6 R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[ 11 C]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[ 11 C]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[ 11 C]methyl-1-piperazinyl)methyl]-1H-indole (N-[ 11 C]2a), 5-[ 11 C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O-[ 11 C]2b) and 5-methoxy-3-((4-[ 11 C]methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (N-[ 11 C]2b), 1-((4-isopropylphenyl)sulfonyl)-5-[ 11 C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[ 11 C]2c) and 1-((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[ 11 C]methylpiperazin-1-yl)methyl)-1H-indole (N-[ 11 C]2c), 1-((4-fluorophenyl)sulfonyl)-5-[ 11 C]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1H-indole (O-[ 11 C]2d) and 1-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[ 11 C]methylpiperazin-1-yl)methyl)-1H-indole (N-[ 11 C]2d), were prepared from their O- or N-desmethylated precursors with [ 11 C]CH 3 OTf through O- or N-[ 11 C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [ 11 C]CO 2 and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370-740 GBq/μmol with a total synthesis time of ∼40-min from EOB. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Brain PET scan

    Science.gov (United States)

    ... results on a PET scan. Blood sugar or insulin levels may affect the test results in people with diabetes . PET scans may be done along with a CT scan. This combination scan is called a PET/CT. Alternative Names Brain positron emission tomography; PET scan - brain References Chernecky ...

  14. [[sup 3]H]imidacloprid: synthesis of a candidate radioligand for the nicotinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Latli, B.; Casida, J.E. (California Univ., Berkeley, CA (United States). Dept. of Entomological Sciences)

    1992-08-01

    Imidacloprid is an exceptionally potent insecticide known from physiological studies to act at the nicotinic acetylcholine receptor. To prepare [[sup 3]H]imidacloprid as a candidate radioligand, 6-chloronicotinoyl chloride was reduced with NaB[sup 2]H[sub 4] (in model studies) or NaB[sup 3]H[sub 4] in absolute ethanol to 2-chloro-5-pyridinylmethanol which was transformed to 2-chloro-5-chloromethylpyridine on refluxing with thionyl chloride. Coupling with 4,5-dihydro-N-nitro-1H-imidazol-2-amine then gave [[sup 2]H[sub 2

  15. Evaluation of attenuation correction in cardiac PET using PET/MR.

    Science.gov (United States)

    Lau, Jeffrey M C; Laforest, R; Sotoudeh, H; Nie, X; Sharma, S; McConathy, J; Novak, E; Priatna, A; Gropler, R J; Woodard, P K

    2017-06-01

    Simultaneous acquisition Positron emission tomography/magnetic resonance (PET/MR) is a new technology that has potential as a tool both in research and clinical diagnosis. However, cardiac PET acquisition has not yet been validated using MR imaging for attenuation correction (AC). The goal of this study is to evaluate the feasibility of PET imaging using a standard 2-point Dixon volume interpolated breathhold examination (VIBE) MR sequence for AC. Evaluation was performed in both phantom and patient data. A chest phantom containing heart, lungs, and a lesion insert was scanned by both PET/MR and PET/CT. In addition, 30 patients underwent whole-body 18 F-fluorodeoxyglucose PET/CT followed by simultaneous cardiac PET/MR. Phantom study showed 3% reduction of activity values in the myocardium due to the non-inclusion of the phased array coil in the AC. In patient scans, average standardized uptake values (SUVs) obtained by PET/CT and PET/MR showed no significant difference (n = 30, 4.6 ± 3.5 vs 4.7 ± 2.8, P = 0.47). There was excellent per patient correlation between the values acquired by PET/CT and PET/MR (R 2  = 0.97). Myocardial SUVs PET imaging using MR for AC shows excellent correlation with myocardial SUVs obtained by standard PET/CT imaging. The 2-point Dixon VIBE MR technique can be used for AC in simultaneous PET/MR data acquisition.

  16. Application of PET and PET/CT imaging for cancer screening

    International Nuclear Information System (INIS)

    Chen Yenkung; Hu Fenglan; Shen Yehyou; Liao, A.C.; Hung, T.Z.; Su, Chentau; Chen Liangkuang

    2004-01-01

    The aim of this study was to evaluate the potential application of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) and PET/CT for cancer screening in asymptomatic individuals. Methods: The subjects consisted of 3631 physical check up examinees (1947 men, 1684 women; mean age ±SD, 52.1±8.2 y) with non-specific medical histories. Whole-body FDG PET (or PET/CT), ultrasound and tumor markers were performed on all patients. Focal hypermetabolic areas with intensities equal to or exceeding the level of FDG uptake in the brain and bladder were considered abnormal and interpreted as neoplasia. Follow-up periods were longer than one year. Results: Among the 3631 FDG PET (including 1687 PET/CT), ultrasound and tumor markers examinations, malignant tumors were discovered in 47 examinees (1.29%). PET findings were true-positive in 38 of the 47 cancers (80.9%). In addition, 32 of the 47 cancers were performed with the PET-CT scan. PET detected cancer lesions in 28 of the 32 examinees. However, the CT detected cancer lesions in only 15 of 32 examinees. Conclusion: The sensitivity of FDG PET in the detection of a wide variety of cancers is high. Most cancer can be detected with FDG PET in a resectable stage. CT of the PET/CT for localization and characteristics of the lesion shows an increased specificity of the PET scan. Using ultrasound and tumor markers may complement the PET scan in cancer screening for hepatic and urologic neoplasms. (authors)

  17. 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...

  18. Improved receptor analysis in PET using a priori information from in vitro binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Litton, J.-E.; Hall, H.; Blomqvist, G. [Department of Clinical Neuroscience, Karolinska Hospital, S-171 76 Stockholm (Sweden)

    1997-08-01

    An accurate determination of non-specific binding is required for the analysis of in vitro and in vivo receptor binding data. For some radioligands the non-specific binding is of the same magnitude as the specific binding. Furthermore, in vitro measurements have shown that the non-specific binding can be different in different brain regions. If this is the case in a PET study for determining B{sub max} and K{sub d}, a correction for the non-specific binding has to be applied. The aim of the present communication is to present a means for determining corrected B{sub max} and K{sub d} with Scatchard analysis using in vitro binding studies. The influence of non-specific binding on the free and specifically bound radioligand is expressed with the aid of a correction factor, which can be calculated from measurable quantities. Introduction of the corrected free and specifically bound radioligand should give binding parameters closer to reality than previously obtained results. (author)

  19. 2-[18 F]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) findings of chronic expanding intrapericardial hematoma: a potential interpretive pitfall that mimics a malignant tumor

    Science.gov (United States)

    2013-01-01

    A 77-year-old man who had undergone mitral valve replacement 5 years previously presented with an intrapericardial mass. Computed tomography and magnetic resonance imaging showed that the mass lesion contained hematoma components. Positron-emission tomography (PET) with 2-[18 F] fluoro-2-deoxy-d-glucose (FDG) revealed uptake in the peripheral rim of the mass. These findings suggested the presence of hematoma associated with a malignant lesion. Surgical resection was performed, and the histological diagnosis was chronic expanding intrapericardial hematoma without neoplastic changes. Chronic expanding intrapericardial hematoma is a rare disease but should be considered when an expanding mass is found in a patient after cardiac surgery. The FDG-PET findings of chronic expanding hematomas, including FDG uptake in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall that mimics a malignant tumor. PMID:23324446

  20. Cancer screening with FDG-PET

    International Nuclear Information System (INIS)

    Ide, M.

    2006-01-01

    Aim: This study is based on medical health check-up and cancer screening on of a medical health club using PET, MRI, spiral CT and other conventional examinations. Methods: Between October 1994 and June 2005, 9357 asymptomatic members of the health club participated in 24772 screening session (5693 men and 3664 women, mean age 52.2±10.4 years). Results: Malignant tumors were discovered in 296 of the 9357 participants (3.16%) and 24772 screening sessions (1.19%). The detection rate of our program is much higher than that of mass screening in Japan. The thyroid, lung, colon and breast cancers were PET positive, but the prostate, renal and bladder cancers were generally PET negative. Conclusion: FDG-PET has the potential to detect a wide variety of cancers at curable stages in asymptomatic individuals. To reduce false-positive and false-negative results of PET examination, there is a need of experienced radiologist and/or oncologists who had training in the wide aspect of FDG-PET. FDG-PET has limitations in the detection of urological cancers, cancers of low cell density, small cancers and hypo metabolic or FDG non-avid cancers. Therefore, conventional examinations and/or PET/CT are also needed for cancer screening in association with FDG-PET

  1. PET imaging in breast cancer

    International Nuclear Information System (INIS)

    Bombardieri, E.; Crippa, F.

    2001-01-01

    The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18 F has the advantages of the a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complete other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. These statements are coming from the examination of more than 2000 breast cancer detection

  2. 67Ga(NODASA): a new potential bifunctional radioligand for coupling to peptides

    International Nuclear Information System (INIS)

    Andre, J.P.; Maecke, H.R.; Zehnder, M.; Macko, L.; Kaspar, A.

    1998-01-01

    A new bifunctional chelator NODASA (1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) has been synthesised and its Ga(III) complex was crystallographically characterized by X-ray diffraction. The complex showed to be stable in serum and in acidic conditions and its stability constant was determined using a competition method with an auxiliary ligand. The conjugation of Ga(NODASA) to a model aminoacidamide proved the feasibility of a prelabelling approach. (author)

  3. Positron emission tomography (PET) for oncologic applications in oral region

    International Nuclear Information System (INIS)

    Shozushima, Masanori; Terasaki, Kazunori

    2004-01-01

    A rapidly emerging clinical application of positron emission tomography (PET) is the detection of cancer with radionuclide tracer, because it provides information unavailable by ultrasound, computed tomography or magnetic resonance imaging. The most commonly used radiotracer for PET oncologic imaging is fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG). Early studies show PET has potential value in viewing the region of the tumor, detecting, staging, grading, monitoring response to anticancer therapy, and differentiating recurrent or residual disease from post treatment changes. However, limitations of FDG-PET in the head and neck region, namely, physiological FDG uptake in the salivary glands and palatine tonsils, have been reported, increasing the false-positive rates in image interpretation. This review was designed to address these distinctions of oral cancer PET imaging: specialization of PET equipment, cancer cell metabolism, proliferation and tracers, clinical diagnosis of oral cancer with PET, pitfalls in oncologic diagnosis with FDG-PET imaging. (author)

  4. PET reconstruction

    International Nuclear Information System (INIS)

    O'Sullivan, F.; Pawitan, Y.; Harrison, R.L.; Lewellen, T.K.

    1990-01-01

    In statistical terms, filtered backprojection can be viewed as smoothed Least Squares (LS). In this paper, the authors report on improvement in LS resolution by: incorporating locally adaptive smoothers, imposing positivity and using statistical methods for optimal selection of the resolution parameter. The resulting algorithm has high computational efficiency relative to more elaborate Maximum Likelihood (ML) type techniques (i.e. EM with sieves). Practical aspects of the procedure are discussed in the context of PET and illustrations with computer simulated and real tomograph data are presented. The relative recovery coefficients for a 9mm sphere in a computer simulated hot-spot phantom range from .3 to .6 when the number of counts ranges from 10,000 to 640,000 respectively. The authors will also present results illustrating the relative efficacy of ML and LS reconstruction techniques

  5. Potential role of combined FDG PET/CT & contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity.

    Science.gov (United States)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D'Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-04-01

    To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Potential role of combined FDG PET/CT and contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity

    International Nuclear Information System (INIS)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D’Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-01-01

    Purpose: To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. Materials and methods: A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Results: Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Conclusion: Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended.

  7. Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance

    International Nuclear Information System (INIS)

    Hendrickson, Kristi; Phillips, Mark; Smith, Wade; Peterson, Lanell; Krohn, Kenneth; Rajendran, Joseph

    2011-01-01

    Background and purpose: Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer . Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control . Advanced radiation treatment planning (RTP) and delivery techniques such as intensity modulated radiation therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP). Materials and methods: FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for 10 of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients. Result: A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included. Conclusion: Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications.

  8. Simultaneous PET-MR acquisition and MR-derived motion fields for correction of non-rigid motion in PET

    International Nuclear Information System (INIS)

    Tsoumpas, C.; Mackewn, J.E.; Halsted, P.; King, A.P.; Buerger, C.; Totman, J.J.; Schaeffter, T.; Marsden, P.K.

    2010-01-01

    Positron emission tomography (PET) provides an accurate measurement of radiotracer concentration in vivo, but performance can be limited by subject motion which degrades spatial resolution and quantitative accuracy. This effect may become a limiting factor for PET studies in the body as PET scanner technology improves. In this work, we propose a new approach to address this problem by employing motion information from images measured simultaneously using a magnetic resonance (MR) scanner. The approach is demonstrated using an MR-compatible PET scanner and PET-MR acquisition with a purpose-designed phantom capable of non-rigid deformations. Measured, simultaneously acquired MR data were used to correct for motion in PET, and results were compared with those obtained using motion information from PET images alone. Motion artefacts were significantly reduced and the PET image quality and quantification was significantly improved by the use of MR motion fields, whilst the use of PET-only motion information was less successful. Combined PET-MR acquisitions potentially allow PET motion compensation in whole-body acquisitions without prolonging PET acquisition time or increasing radiation dose. This, to the best of our knowledge, is the first study to demonstrate that simultaneously acquired MR data can be used to estimate and correct for the effects of non-rigid motion in PET. (author)

  9. Imaging and PET - PET/CT imaging

    International Nuclear Information System (INIS)

    Von Schulthess, G.K.; Hany, Th.F.

    2008-01-01

    PET/CT has grown because the lack of anatomic landmarks in PET makes 'hardware-fusion' to anatomic cross-sectional data extremely useful. Addition of CT to PET improves specificity, but also sensitivity, and adding PET to CT adds sensitivity and specificity in tumor imaging. The synergistic advantage of adding CT is that the attenuation correction needed for PET data can also be derived from the CT data. This makes PET-CT 25-30% faster than PET alone, leading to higher patient throughput and a more comfortable examination for patients typically lasting 20 minutes or less. FDG-PET-CT appears to provide relevant information in the staging and therapy monitoring of many tumors, such as lung carcinoma, colorectal cancer, lymphoma, gynaecological cancers, melanoma and many others, with the notable exception of prostatic cancer. for this cancer, choline derivatives may possibly become useful radiopharmaceuticals. The published literature on the applications of FDG-PET-CT in oncology is still limited but several designed studies have demonstrated the benefits of PET-CT. (authors)

  10. 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.

  11. Missed causative tumors in diagnosing tumor-induced osteomalacia with (18)F-FDG PET/CT: a potential pitfall of standard-field imaging.

    Science.gov (United States)

    Kaneuchi, Yoichi; Hakozaki, Michiyuki; Yamada, Hitoshi; Hasegawa, Osamu; Tajino, Takahiro; Konno, Shinichi

    2016-01-01

    We describe herein two tumor-induced osteomalacia (TIO) cases for whom the causative lesions, located in their popliteal fossa, that were not identified in the standard field of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT), which usually images only the head, trunk, and proximal parts of the extremities. A 47 years old Japanese man with multiple pathological fractures due to osteomalacia, accompanied by muscle weakness, hypophosphatemia, and an elevation of alkaline phosphatase (ALP) was referred to our hospital. A (18)F-FDG PET/CT scan was performed, but no (18)F-FDG uptake was detected in the standard field of imaging. Magnetic resonance imaging revealed a small subcutaneous tumor (1.9×1.2×0.6cm) of the left posteriomedial knee, displaying uniform enhancement on gadolinium-enhanced T1-weighted fat-suppression imaging. The tumor was resected widely and diagnosed as phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). The other patient was a 31 years old Japanese woman with multiple pathological fractures, hypophosphatemia and elevated of ALP and was referred to our hospital on suspicion of TIO. Although the causative lesion was not identified in the standard field of (18)F-FDG PET/CT, (18)F-FDG uptake (SUVmax 2.9) was detected on the right knee in the additional whole-body (18)F-FDG PET/CT. Magnetic resonance imaging revealed a soft-tissue tumor (6.4×4.1×2.9cm) in the right posterior knee. Following biopsy, the tumor was marginally resected, and was pathologically diagnosed as PMTMCT. Once patients are suspected to have TIO, a whole-body nuclear imaging study such as (18)F-FDG PET/CT should be performed, in order not to miss the hidden causative tumor, especially occurring in the distal extremities.

  12. Trends in PET imaging

    International Nuclear Information System (INIS)

    Moses, William W.

    2000-01-01

    Positron Emission Tomography (PET) imaging is a well established method for obtaining information on the status of certain organs within the human body or in animals. This paper presents an overview of recent trends PET instrumentation. Significant effort is being expended to develop new PET detector modules, especially those capable of measuring depth of interaction. This is aided by recent advances in scintillator and pixellated photodetector technology. The other significant area of effort is development of special purpose PET cameras (such as for imaging breast cancer or small animals) or cameras that have the ability to image in more than one modality (such as PET / SPECT or PET / X-Ray CT)

  13. Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae [Kyungpook National University Medical Center and School of Medicine, Daegu (Korea, Republic of)

    2016-03-15

    This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV{sub max} and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV{sub max} were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV{sub max} was 4.7. In 16 patients who underwent follow-up PET/CT, SUV{sub max} was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment.

  14. The motor evoked potential in aids and HAM/TSP State of the evidence El potencial evocado motor en SIDA y HAM/PET

    Directory of Open Access Journals (Sweden)

    Fidias E. Leon-Sarmiento

    2009-12-01

    datos MEDLINE, que abarcó el período de 1985 a 2008; se incluyeron los términos "HTLV-I, HTLV-II, HTLV-III and HIV, HIV1, HIV2, evoked potential, motor evoked potential, high voltage electrical stimulation, transcranial magnetic stimulation, magnetic stimulation, corticomotor physiology, motor pathways, acquired immunodeficiency syndrome, AIDS, SIDA, tropical spastic paraparesis, HTLV-I-associated myelopathy, HAM, TSP, and HAM/TSP". RESULTADOS: Se obtuvieron 18 artículos publicados en inglés, español, portugués, francés y japonés. El tiempo de conducción central es el único parámetro que se ha estudiado en individuos seropositivos a retrovirus humanos. Las investigaciones hechas en HAM/PET apoyan el compromiso del tracto piramidal, principalmente a nivel dorso-lumbar, de manera centrípeta. En SIDA, el compromiso parece ser mas prominente a nivel cortical, siguiendo un patrón centrifugo. CONCLUSION: El conocer las diferencias en el compromiso y anormalidades del tracto corticoespinal de los pacientes con SIDA y HAM/TSP podrán ser útiles para reorientar la neurorehabilitación temprana en estos desórdenes neurodegenerativos asociados a retrovirus. De otro lado, evaluaciones mas sensibles y sofisticadas del sistema piramidal, que permitan detectar cambios tempranos en los circuitos talamocorticoganglionicos serán mandatarios de realizar a partir de la fecha, bien sea que los individuos estén asintomáticos o no, en estadios clínicos donde las fibras corticoespinales rápidas no estén aun comprometidas.

  15. Imaging micro-glial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by Positron Emission Tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714

    International Nuclear Information System (INIS)

    Abourbeh, Galith; Theze, Benoit; Dubois, Albertine; Tavitian, Bertrand; Boisgard, Raphael; Maroy, Renaud; Brulon, Vincent; Fontyn, Yoann; Dolle, Frederic

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated micro-glia/macrophages play a key role in the immuno-pathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Micro-glia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of micro-glial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuro-inflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [ 18 F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [ 18 F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [ 18 F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl) - isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [ 18 F]DPA-714, neuro-inflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuro-inflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuro-inflammation for detection, monitoring, and research in MS. (authors)

  16. PET/MRI for Neurological Applications

    Science.gov (United States)

    Catana, Ciprian; Drzezga, Alexander; Heiss, Wolf-Dieter; Rosen, Bruce R.

    2013-01-01

    PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MR data acquisition allows the spatial and temporal correlation of the measured signals, opening up opportunities impossible to realize using stand-alone instruments. This paper reviews the methodological improvements and potential neurological and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MR data to improve the PET data quantification. On the MR side, we present how improved PET quantification could be used to validate a number of MR techniques. Finally, we describe promising research, translational and clinical applications that could benefit from these advanced tools. PMID:23143086

  17. PET/MRI for neurologic applications.

    Science.gov (United States)

    Catana, Ciprian; Drzezga, Alexander; Heiss, Wolf-Dieter; Rosen, Bruce R

    2012-12-01

    PET and MRI provide complementary information in the study of the human brain. Simultaneous PET/MRI data acquisition allows the spatial and temporal correlation of the measured signals, creating opportunities impossible to realize using stand-alone instruments. This paper reviews the methodologic improvements and potential neurologic and psychiatric applications of this novel technology. We first present methods for improving the performance and information content of each modality by using the information provided by the other technique. On the PET side, we discuss methods that use the simultaneously acquired MRI data to improve the PET data quantification. On the MRI side, we present how improved PET quantification can be used to validate several MRI techniques. Finally, we describe promising research, translational, and clinical applications that can benefit from these advanced tools.

  18. Kinetic modeling in PET imaging of hypoxia

    Science.gov (United States)

    Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

    2014-01-01

    Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200

  19. PET / MRI vs. PET / CT. Indications Oncology

    International Nuclear Information System (INIS)

    Oliva González, Juan P.

    2016-01-01

    Hybrid techniques in Nuclear Medicine is currently a field in full development for diagnosis and treatment of various medical conditions. With the recent advent of PET / MRI much it speculated about whether or not it is superior to PET / CT especially in oncology. The Conference seeks to clarify this situation by dealing issues such as: State of the art technology PET / MRI; Indications Oncology; Some clinical cases. It concludes by explaining the oncological indications of both the real and current situation of the PET / MRI. (author)

  20. Preparation of steroid radioligands for ultrafiltration assays by a solid-phase transport globulin method using concanavalin A-Sepharose

    International Nuclear Information System (INIS)

    Hiramatsu, R.; Nisula, B.C.

    1985-01-01

    Concanavalin A-Sepharose (Con A-Sepharose) was applied to separate non-protein-bound and albumin-bound radioactive impurities from steroid radioligands. Con A-Sepharose gel, plasma, and steroid radioligand were mixed, incubated, and then washed with buffer. This method was compared with an affinity diafiltration method which separates non-protein-bound radioactive impurities with a filter membrane. 3 H-Water and 3 H-estrone sulfate, chosen to serve as molecules representative of non-protein-bound and albumin-bound impurities, were removed quite effectively by the Con A-Sepharose method, while 85% of 3 H-estrone sulfate could not be removed by the diafiltration method. Plasma unbound cortisol (F) and testosterone (T) values determined by ultrafiltration using 3 H-F and 3 H-T prepared by the Con A-Sepharose method were significantly lower than those determined using the radioligands unprocessed or prepared by the diafiltration method. The whole procedure of the Con A-Sepharose method takes only 3-4 hours. This method is a simple, rapid, and effective technique for preparation of steroid radioligands for plasma protein binding studies

  1. Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging

    NARCIS (Netherlands)

    Rijks, L. J.; Busemann Sokole, E.; Stabin, M. G.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1998-01-01

    This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous

  2. Radiosynthesis, evaluation and preclinical studies of a new 5HT2A radioligand

    International Nuclear Information System (INIS)

    Mertens, J.; Terriere, D.; Baeken, C.; D'Haenan, H.; Flamen, P.; Bossuyt, A.; Leysen, J.

    1998-01-01

    123 I-5-I-R91150, a radioiodinated analogue of R91150 (a ligand (antagonist) of Janssen Research Foundation), showing high affinity and selectivity for 5HT 2A receptors, was developed as a potential in vivo 5HT 2A receptor tracer for SPECT. The applied radiochemistry, whereby the radioiodine was substituted on the 5 - position of the benzamide ring, allowed to obtain the tracer with high specific activity and high purity. In vitro and in vivo rat studies revealed that the new tracer bound reversibly with the required high affinity (Kd=0.1 nM) and high selectivity (a factor ranging from 10000 to at least 50 vis a vis other receptors) to 5HT 2A receptors. In young normal subjects the major part of the 123 I-5-I-R91150 radioactivity in the brain is present in cortical areas. Cortical area to cerebellum activity ratio reaches an equilibrium value of about 1.8 around 90 min. till 4 hours p.i.. This binding was specific and reversible. The cortical activity reflects a distribution in the brain similar to that of the mapping of 5HT 2A receptors from post mortem studies. These findings suggested that 123 I-5-I-R91150 allows imaging and quantitative estimation with SPECT and could be used for further clinical studies. The radiobromine analogue was synthetised as a potential PET tracer. (author)

  3. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming

    2015-01-01

    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...

  4. Metabolic liver function in humans measured by 2-(18)F-fluoro-2-deoxy-D-galactose PET/CT-reproducibility and clinical potential

    DEFF Research Database (Denmark)

    Bak-Fredslund, Kirstine P; Lykke Eriksen, Peter; Munk, Ole L

    2017-01-01

    Background: PET/CT with the radioactively labelled galactose analogue 2-18F-fluoro-2-deoxy-D-galactose (18F-FDGal) can be used to quantify the hepatic metabolic function and visualise regional metabolic heterogeneity. We determined the day-to-day variation in humans with and without liver disease....... Furthermore, we examined whether the standardised uptake value (SUV) of 18F-FDGal from static scans can substitute the hepatic systemic clearance of 18F- FDGal (Kmet, mL blood/min/mL liver tissue/) quantified from dynamic scans as measure of metabolic function. Four patients with cirrhosis and six healthy...... subjects underwent two 18F-FDGal PET/CT scans within a median interval of 15 days for determination of day-to-day variation. The correlation between Kmet and SUV was examined using scan data and measured arterial blood concentrations of 18F-FDGal (blood samples) from 14 subjects from previous studies...

  5. Potential use of "1"8F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report

    International Nuclear Information System (INIS)

    Taniguchi, Yuki; Takahashi, Miwako; Momose, Toshimitsu; Matsudaira, Ko; Oka, Hiroyuki

    2016-01-01

    Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ("1"8F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, "1"8F-FDG-PET imaging revealed the uptake of "1"8F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using "1"8F-FDG-PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. (orig.)

  6. Dual-time FDG-PET/CT in patients with potential breast cancer recurrence: Head-to-head comparison with CT and bone scintigraphy

    DEFF Research Database (Denmark)

    Baun, Christina; Falch Braas, Kirsten; Gerke, Oke

    of six hours and had a blood glucose level less than 8 mmol/l prior to injection of 4 MBq/kg of FDG. Imaging was performed 1 and 3 hours (±5 mins) after injection. At both time-points a low-dose CT from the skull to the proximal femur was obtained followed by a 3D PET-scan of the same area. The duration...... administered with a flow of 3.0 ml/s and a delay of 60 seconds. Bone scintigraphy. The patients were injected with 700 MBq 99mTc-DPD 3 to 4 hours prior to whole body imaging. In the waiting period the patients were asked to drink approx. 1 litre of clear liquids. Positive findings with any of the three...... had sensitivities of 67% and 81% and specificities of 100% and 48%, respectively. Conclusion: These interim results suggest that FDG PET/CT may have a role in the diagnostic work-up of patients with suspected recurrent breast cancer. The 3-hour FDG-PET scan may be diagnostically superior to the other...

  7. Potential use of {sup 18}F-FDG-PET/CT to visualize hypermetabolism associated with muscle pain in patients with adult spinal deformity: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yuki [The University of Tokyo Hospital, Department of Orthopedic Surgery, Bunkyo-ku, Tokyo (Japan); Takahashi, Miwako; Momose, Toshimitsu [The University of Tokyo, Division of Nuclear Medicine, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); Matsudaira, Ko; Oka, Hiroyuki [The University of Tokyo, Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, Tokyo (Japan)

    2016-11-15

    Patients with adult spinal deformity (ASD) are surgically treated for pain relief; however, visualization of the exact origin of the pain with imaging modalities is still challenging. We report the first case of a 60-year-old female patient who presented with painful degenerative kyphoscoliosis and was evaluated with flourine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT) preoperatively. Because her low back pain was resistant to conservative treatment, she was treated with posterior spinal correction and fusion surgery from Th2 to the ilium. One year after the surgery, her low back pain had disappeared completely. In accordance with her clinical course, {sup 18}F-FDG-PET imaging revealed the uptake of {sup 18}F-FDG in the paravertebral muscles preoperatively and showed the complete absence of uptake at 1 year after surgery. The uptake site coincided with the convex part of each curve of the lumbar spine and was thought to be the result of the increased activity of paravertebral muscles due to their chronic stretched state in the kyphotic posture. This case report suggests the possibility of using {sup 18}F-FDG-PET/CT to visualize increased activity in paravertebral muscles and the ensuing pain in ASD patients. (orig.)

  8. Pets and Parasites

    Science.gov (United States)

    ... good news is that this rarely happens. Most pet-to-people diseases can be avoided by following a few ... your doctor Can a parasite cause death in people and pets? Can human disease from a parasite be treated ...

  9. Heart PET scan

    Science.gov (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  10. [Principles of PET].

    Science.gov (United States)

    Beuthien-Baumann, B

    2018-05-01

    Positron emission tomography (PET) is a procedure in nuclear medicine, which is applied predominantly in oncological diagnostics. In the form of modern hybrid machines, such as PET computed tomography (PET/CT) and PET magnetic resonance imaging (PET/MRI) it has found wide acceptance and availability. The PET procedure is more than just another imaging technique, but a functional method with the capability for quantification in addition to the distribution pattern of the radiopharmaceutical, the results of which are used for therapeutic decisions. A profound knowledge of the principles of PET including the correct indications, patient preparation, and possible artifacts is mandatory for the correct interpretation of PET results.

  11. In vivo evaluation of [123I]mZIENT as a SPECT radioligand for the serotonin transporter

    International Nuclear Information System (INIS)

    Batis, Jeffery; Barret, Olivier; Alagille, David; Koren, Andrei O.; Stehouwer, Jeffrey S.; Cosgrove, Kelly; Goodman, Mark; Seibyl, John; Tamagnan, Gilles

    2012-01-01

    Introduction: In vivo imaging of the serotonin transporter continues to be a valuable tool in drug development and in monitoring diseases that alter serotonergic function. The purposes of this study were to: 1) evaluate the test/retest reproducibility of [ 123 I] 2β-Carbomethoxy-3β-(3′-((Z)-2-iodoethenyl)phenyl)nortropane ([ 123 I]mZIENT); and 2) to assess displacement of [ 123 I]mZIENT following administration of SERT specific drugs. Methods: Six female baboons (Papio anubis) were scanned following i.v. administration of [ 123 I]mZIENT. The regional binding potential (BP nd ) was determined using a simplified reference tissue model, with the cerebellum used as a reference region. The test/retest reproducibility of BP nd was determined following repeated injection of [ 123 I]mZIENT on a different day. To assess the displacement of [ 123 I]mZIENT from SERT, citalopram (0.01–5 mg/kg) or sertraline (0.01–0.5 mg/kg) was given as iv bolus at ∼ 4 h following administration of [ 123 I]mZIENT. Results: The test/retest variability of BP nd was less than 10% for all SERT-rich brain regions. Estimates of ED50 for displacement of [ 123 I]mZIENT in SERT-rich regions were consistent with previous reports for the [ 11 C] analog of [ 123 I]mZIENT. Both citalopram and sertraline displaced [ 123 I]mZIENT from SERT in a dose-dependent manner, with maximal observed displacements of greater than 80% in the diencephalon and greater than 75% in brainstem for both citalopram and sertraline. Conclusions: [ 123 I] mZIENT demonstrates good test–retest reproducibility; and initial displacement studies suggest that this compound is highly selective for SERT. Overall, this radioligand has favorable characteristics for use in drug development studies and/or longitudinal studies interrogating SERT.

  12. Dopamine receptors in pituitary adenomas: PET visualization with 11C-N-methylspiperone

    International Nuclear Information System (INIS)

    Muhr, C.; Bergstroem, M.L.; Lundberg, P.O.; Bergstroem, K.H.; Hartvig, P.; Lundqvist, H.; Antoni, G.; Langstroem, B.

    1986-01-01

    Two patients with pituitary tumors were examined with positron emission tomography (PET) after intravenous administration of 11C-N-methylspiperone. In repeat studies the patients were given 1 mg of intravenous haloperidol prior to the administration of the radioligand to block the dopamine receptors. High uptakes of the radiolabeled ligand were seen in one of the tumors. With haloperidol pretreatment the uptake was lower, probably mainly showing the remaining unspecific binding. The most marked uptake and the largest effect of haloperidol pretreatment was seen in a patient with a hormonally active prolactinoma. Dopamine receptor binding in pituitary tumors can be demonstrated in vivo with PET, and quantification of this binding is possible using a compartmental model. This technique may be useful in improving our understanding of the variable response to medical treatment of prolactinomas with dopamine agonists as well as in the prediction of the effect of such treatment

  13. Evaluation of dopamine transporters and D2 receptors in hemiparkinsonian rat brains in vivo using consecutive PET scans of [18F]FPCIT and [18F]fallypride

    International Nuclear Information System (INIS)

    Choi, Jae Yong; Kim, Chul Hoon; Jeon, Tae Joo; Cho, Won Gil; Lee, Jin Suk; Lee, Soo Jin; Choi, Tae Hyun; Kim, Byoung Soo; Yi, Chi Hoon; Seo, Youngbeom; Yi, Dae Ik; Han, Sang Jin; Lee, Minkyung; Kim, Dong Goo; Lee, Jong Doo; An, Gwangil

    2012-01-01

    The aim of this study was to investigate dopaminergic function in unilaterally lesioned 6-OHDA rats by dual PET radioligands: [ 18 F]FPCIT (a dopamine transporter imaging radioligand) and [ 18 F]fallypride (a dopamine D2 receptors imaging radioligand). As a result, the brain uptake of [ 18 F]FPCIT was significantly reduced and that of [ 18 F]fallypride was increased in the ipsilateral striatum (lesion side) of the 6-OHDA rats. These findings implicated that dopamine transporter is down-regulated and dopamine D2 receptor is up-regulated in this hemiparkinsonian rat model. - Highlights: ► The dopaminergic integrity in unilateral 6-OHDA was evaluated by dual PET tracers. ► The brain uptake and BP ND of [ 18 F]FPCIT was greatly decreased. ► The brain uptake and BP ND [ 18 F]fallypride was slightly increased. ► DAT are down-regulated and D2R are up-regulated.

  14. Pyrethroid insecticides and radioligand displacement from the GABA receptor chloride ionophore complex

    International Nuclear Information System (INIS)

    Crofton, K.M.; Reiter, L.W.; Mailman, R.B.

    1987-01-01

    Radioligand binding displacement studies were conducted to determine the effects of Type I and II pyrethroids on 3 H-flunitrazepam (FLU), 3 H-muscimol (MUS), and ( 35 S-t-butylbicyclophosphorothionate (TBPS) binding. Competition experiments with 3 H-FLU and 3 H-MUS indicate a lack of competition for binding by the pyrethroids. Type I pyrethroids failed to compete for the binding of ( 35 S-TBPS at concentrations as high as 50 pM. Type II pyrethroids inhibited ( 35 S-TBPS binding to rat brain synaptosomes with Ki values ranging from 5-10 pM. The data presented suggest that the interaction of Type II pyrethroids with the GABA receptor-ionophore complex is restricted to a site near the TBPS/picrotoxinin binding site

  15. [3H]imidacloprid: synthesis of a candidate radioligand for the nicotinic acetylcholine receptor

    International Nuclear Information System (INIS)

    Latli, B.; Casida, J.E.

    1992-01-01

    Imidacloprid is an exceptionally potent insecticide known from physiological studies to act at the nicotinic acetylcholine receptor. To prepare [ 3 H]imidacloprid as a candidate radioligand, 6-chloronicotinoyl chloride was reduced with NaB 2 H 4 (in model studies) or NaB 3 H 4 in absolute ethanol to 2-chloro-5-pyridinylmethanol which was transformed to 2-chloro-5-chloromethylpyridine on refluxing with thionyl chloride. Coupling with 4,5-dihydro-N-nitro-1H-imidazol-2-amine then gave [ 2 H 2 ]imidacloprid incorporating about 95% of the deuterium or [ 3 H 2 ]imidacloprid (25 Ci/mmol) in 80% radiochemical yield. In studies not detailed here [ 3 H] imidacloprid was found to undergo high affinity, specific and saturable binding to a site in insect brain. (author)

  16. 125I-labeled 8-phenylxanthine derivatives: antagonist radioligands for adenosine A1 receptors

    International Nuclear Information System (INIS)

    Linden, J.; Patel, A.; Earl, C.Q.; Craig, R.H.; Daluge, S.M.

    1988-01-01

    A series of 8-phenylxanthine derivatives has been synthesized with oxyacetic acid on the para phenyl position to increase aqueous solubility and minimize nonspecific binding and iodinatable groups on the 1- or 3-position of the xanthine ring. The structure-activity relationship for binding of these compounds to A1 adenosine receptors of bovine and rat brain and A2 receptors of human platelets was examined. The addition of arylamine or photosensitive aryl azide groups to the 3-position of xanthine had little effect on A1 binding affinity with or without iodination, whereas substitutions at the 1-position caused greatly reduced A1 binding affinity. The addition of an aminobenzyl group to the 3-position of the xanthine had little effect on A2 binding affinity, but 3-aminophenethyl substitution decreased A2 binding affinity. Two acidic 3-(arylamino)-8-phenylxanthine derivatives were labeled with 125 I and evaluated as A1 receptor radioligands. The new radioligands bound to A1 receptors with KD values of 1-1.25 nM. Specific binding represented over 80% of total binding. High concentrations of NaCl or other salts increased the binding affinity of acidic but not neutral antagonists, suggesting that interactions between ionized xanthines and receptors may be affected significantly by changes in ionic strength. On the basis of binding studies with these antagonists and isotope dilution with the agonist [ 125 I]N6-(4-amino-3-iodobenzyl)adenosine, multiple agonist affinity states of A1 receptors have been identified

  17. PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow

    International Nuclear Information System (INIS)

    Hassoun, Wadad; Ginovart, Nathalie; Zimmer, Luc; Gualda, Veronique; Bonnefoi, Frederic; Le Cavorsin, Marion; Leviel, Vincent

    2003-01-01

    Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [ 11 C]raclopride (BP raclo ), a radioligand with good specificity for dopamine (DA) receptors of the D 2 type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg -1 h -1 ; i.m.) and anaesthetised with halothane (1.5%). Non-specific binding was evaluated in the cerebellum. In the striatum of both sides, the BP raclo was unmodified by ketamine anaesthesia when compared with awake animals. In contrast, a large increase in BP raclo was observed under halothane anaesthesia. The non-specific binding of [ 11 C]raclopride, evaluated in the cerebellum, was also unchanged under ketamine anaesthesia but greatly increased under halothane anaesthesia. To evaluate whether changes in the cerebral blood flow (CBF) resulting from the different experimental situations could be at the root of these discrepancies, injections of [ 15 O]H 2 O were performed; measurements revealed a drastically increased CBF under halothane anaesthesia and a slight enhancement under ketamine anaesthesia, when compared with the waking state. These results are the first to be obtained on this topic in awake cats, and show that the BP raclo is greatly dependent on alterations in the CBF. (orig.)

  18. Evaluation of the Dopamine Hypothesis of ADHD with PET Brain Imaging

    International Nuclear Information System (INIS)

    Swanson, James

    2010-01-01

    The Dopamine (DA) Hypothesis of ADHD (Wender, 1971; Levy, 1990) suggests that abnormalities in the synaptic mechanisms of DA transmission may be disrupted, and specific abnormalities in DA receptors and DA transporters (DAT) have been proposed (see Swanson et al, 1998). Early studies with small samples (e.g., n = 6, Dougherty et al, 1999) used single photon emission tomography (SPECT) and the radioligand (123I Altropane) to test a theory that ADHD may be caused by an over expression of DAT and reported 'a 70% increase in age-corrected dopamine transporter density in patients with attention deficit hyperactivity disorder compared with healthy controls' and suggested that treatment with stimulant medication decreased DAT density in ADHD patients and corrected an underlying abnormality (Krause et al, 2000). The potential importance of these findings was noted by Swanson (1999): 'If true, this is a major finding and points the way for new investigations of the primary pharmacological treatment for ADHD (with the stimulant drugs - e.g., methylphenidate), for which the dopamine transporter is the primary site of action. The potential importance of this finding demands special scrutiny'. This has been provided over the past decade using Positron Emission Tomography (PET). Brain imaging studies were conducted at Brookhaven National Laboratory (BNL) in a relatively large sample of stimulant-naive adults assessed for DAT (11C cocaine) density and DA receptors (11C raclopride) availability. These studies (Volkow et al, 2007; Volkow et al, 2009) do not confirm the hypothesis of increased DAT density and suggest the opposite (i.e., decreased rather than increased DAT density), and follow-up after treatment (Wang et al, 2010) does not confirm the hypothesis that therapeutic doses of methylphenidate decrease DAT density and suggests the opposite (i.e., increased rather than decreased DAT density). The brain regions implicated by these PET imaging studies also suggest that a

  19. How PET is changing the management of cancer with radiotherapy

    International Nuclear Information System (INIS)

    Mac Manus, M.

    2005-01-01

    Information from PET scanning is transforming the management of many malignancies and the impact of PET is likely to increase further as new indications are recognised. PET is of particular value in patients treated with radiotherapy (RT) with curative intent. These patients rarely undergo invasive surgical staging and therefore imaging is crucial in determining the extent of disease before treatment. More accurate staging with PET means that futile aggressive RT or chcmoRT can be avoided in patients with incurable extensive disease. FDG-PET is of proven value in the staging of common metabolically-active malignancies treated with radiotherapy. These include lung cancer, head and neck cancer, lymphomas and oesophageal carcinoma. It has been shown that PET can improve the selection of patients for radical surgery or radiotherapy in lung cancer and that PET-based staging more accurately predicts survival than conventional staging. For those patients that remain eligible for definitive RT after PET. treatment can be more accurately targeted at the tumour and involved regional nodes. The value of PET for treatment planning is enhanced significantly when PET and CT scans are acquired on a combined PET/CT scanner. Fused PET-CT images can be imported into the radiotherapy planning computer and used to accurately target tumour with the best beam arrangement. After treatment, response may be hard to assess with structural imaging. PET-rcsponse to chemotherapy or radiotherapy in non-small cell lung cancer (NSCLC) predicts survival in NSCLC more accurately than CT response. However, PET has much more potential than imaging with FDG alone can realise. Markers such as FLT can be used to image proliferation in tumours, misonidazole or FAZA can be used to image hypoxia and labeled metabolites of anti-cancer drugs such as 5-FU can be used to study pharmacokinetics. New combinations of radiation and drugs may emerge that can be selected based on biological characteristics of

  20. Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Farde, Lars; Rück, Christian; Varrone, Andrea; Forsberg, Anton; Lindefors, Nils; Halldin, Christer; Lundberg, Johan

    2016-07-30

    The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging

    Science.gov (United States)

    Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

    2012-01-01

    The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 (68Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with 68Ga was achieved in 10 minutes using microwave heating. The labeling efficiency a nd radiochemical purity after purification of 68Ga-DOTA-DG were ~85% and greater than 98%, respectively. In A431 cells, the percentages of 68Ga-DOTA-DG and 18F-FDG uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the mean ± standard deviation of 68Ga-DOTADG uptake values in A431 tumors were 2.38±0.30, 0.75±0.13, and 0.39±0.04 percent of the injected dose per gram of tissue at 10, 30, and 60 minutes after intravenous injection, respectively. μPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after injection of 68Ga-DOTA-DG at a dose of 3.7 MBq. 68Ga-DOTA-DG displayed significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios than 18F-FDG did. Further studies are needed to identify the mechanism of tumor uptake of this new glucosamine-based PET imaging tracer. PMID:23145365

  2. Dynamic comparison of PET imaging performance between state-of-the-art ToF-PET/CT and ToF-PET/MR scanners

    International Nuclear Information System (INIS)

    Delso, Gaspar; Deller, Tim; Khalighi, Mehdi; Veit-Haibach, Patrick; Schulthess, Gustav von

    2014-01-01

    The goal of the present work was to determine the potential for dose reduction in a new clinical ToF-PET/MR scanner. This was achieved by means of long dynamic phantom acquisitions designed to provide a fair comparison of image quality and lesion detectability, as a function of activity, between the new PET/MR system and a state-of-the art PET/CT.

  3. FDG PET imaging dementia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medical School and Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2007-04-15

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia.

  4. FDG PET imaging dementia

    International Nuclear Information System (INIS)

    Ahn, Byeong Cheol

    2007-01-01

    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia

  5. Radiosynthesis and Evaluation of [(11)C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites

    DEFF Research Database (Denmark)

    Jensen, Claus H; Hansen, Hanne D; Bay, Tina

    2017-01-01

    understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report...... autoradiography on sections of pig brain was performed using [(3)H]HOCPCA. In vivo evaluation of [(11)C]HOCPCA showed no brain uptake, possibly due to a limited uptake of HOCPCA by the MCT1 transporter at tracer doses of [(11)C]HOCPCA....

  6. The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning.

    Science.gov (United States)

    Kautzky, A; James, G M; Philippe, C; Baldinger-Melich, P; Kraus, C; Kranz, G S; Vanicek, T; Gryglewski, G; Wadsak, W; Mitterhauser, M; Rujescu, D; Kasper, S; Lanzenberger, R

    2017-06-13

    Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT 1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl- 11 C]WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BP ND ) was divided by dorsal raphe BP ND as a specific measure to highlight rs6295 effects (BP Div ). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BP Div was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT 1A BP ND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.

  7. [11C]CHIBA-1001 as a novel PET ligand for alpha7 nicotinic receptors in the brain: a PET study in conscious monkeys.

    Directory of Open Access Journals (Sweden)

    Kenji Hashimoto

    Full Text Available BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain. METHODOLOGY/PRINCIPAL FINDINGS: A receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg. However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg. Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days; which is a non-human primate model of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.

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

    Science.gov (United States)

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

    2017-07-01

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

  9. Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by (18)F-FLT PET scanning.

    Science.gov (United States)

    Woolthuis, C; Agool, A; Olthof, S; Slart, R H J A; Huls, G; Smid, W M; Schuringa, J J; Vellenga, E

    2011-01-01

    Autologous SCT (auto-SCT) introduces a reduced tolerance to chemotherapy even in patients with adequate engraftment, suggesting long-term effects of the transplantation procedure on the BM capacity. To study the hematopoietic cell compartment after auto-SCT, CD34(+) BM cells (n = 16) from patients at 6-9 months after auto-SCT were studied with regard to the progenitor subsets, colony frequency and cell cycle status. The BM compartments were studied in vivo using PET tracer 3-fluoro-3-deoxy-L-thymidine (¹⁸F-FLT PET). BM CD34(+) cells after auto-SCT were compared with normal CD34(+) cells and showed a phenotypic shift from common myeloid progenitor (CMP mean percentage 3.7 vs 19.4%, P=0.001) to granulocyte-macrophage progenitor (GMP mean percentage 51.8 vs 27.6%, P=0.01). In addition, a reduced clonogenic potential and higher cycling activity especially of the GMP fraction (41% ± 4 in G2/S phase vs 19% ± 2, P = 0.03) were observed in BM after auto-SCT compared with normal. The enhanced cycling activity was confirmed in vivo by showing a significantly higher uptake of the ¹⁸F-FLT PET tracer by the BM compartment. This study shows that auto-SCT results in defects of the hematopoietic compartment at least 6 months after auto-SCT, characterized by changes in the composition of progenitor subsets and enhanced in vitro and in vivo cycling activity.

  10. Mechanism of action in VIVO of some pet radiotracers

    International Nuclear Information System (INIS)

    Sachinidis, J.J.; Egan, G.F.; Berlangieri, S.U.; Scott, A.M.

    1998-01-01

    Full text: Position Emission Tomography (PET) is a technique that utilises position-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. PET studies range from standard image displays that provide indices of physiological function to complex kinetic analysis methods for absolute quantification. This paper will review some of the important PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre, Melbourne and discuss their mechanism of action in vivo. Depending on their mechanism of action, PET radiopharmaceuticals may be divided into two categories. The first category is non-specific radiotracers which follow a biochemical pathway. The second category is specific radioligands which are involved in an interaction with a receptor transporter or a receptor site. Radiopharmaceuticals from the first category may be assessed using a single or two compartmental plasma-tissue model and allow a measurement of tissue extraction or metabolism.[ 15 O] water is a freely diffusable inert which is used for cerebral blood flow measurement; [ 18 F] FDG which follows the initial phases of glucose metabolism but does not enter the Krebs cycle after phosphorylation and therefore is effectively trapped in the cells, can be used for tissue glucose metabolism measurement in oncology, cardiology and neurology; and [ 18 F]fluoromisonidazole which is a bio-reductive drug that in vivo follows an intracellular reduction pathway, can be used for hypoxic tissue measurement in stroke and tumour evaluation. Radiopharmaceuticals from the second category may be assessed using a three-compartment model: - unmetabolised free ligand in plasma, - free ligand in tissue, - and specially bound ligand in tissue. These radiotracers such as [ 11 C] flumazenil, which is an antagonist with high affinity and selectivity for a central benzodiazepine receptors, are used to study the changes in density or affinity of these receptors

  11. Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

    International Nuclear Information System (INIS)

    Herth, Matthias M.; Petersen, Ida Nymann; Hansen, Hanne Demant; Hansen, Martin; Ettrup, Anders; Jensen, Anders A.; Lehel, Szabolcs; Dyssegaard, Agnete; Gillings, Nic; Knudsen, Gitte M.

    2016-01-01

    Introduction: The serotonin 2A receptor (5-HT 2A R) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins and processes in the human brain and several 5-HT 2A R PET antagonist radioligands are available. In contrast to an antagonist radioligand, an agonist radioligand should be able to image the population of functional receptors, i.e., those capable of inducing neuroreceptor signaling. Recently, we successfully developed and validated the first 5-HT 2A R agonist PET tracer, [ 11 C]Cimbi-36, for neuroimaging in humans and herein disclose some of our efforts to develop an 18 F-labeled 5-HT 2A R agonist PET-ligand. Methods and results: Three fluorine containing derivatives of Cimbi-36 were synthesized and found to be potent 5-HT 2A agonists. 18 F-labeling of the appropriate precursors was performed using [ 18 F]FETos, typically yielding 0.2–2.0 GBq and specific activities of 40–120 GBq/μmol. PET studies in Danish landrace pigs revealed that [ 18 F]1 displayed brain uptake in 5-HT 2A R rich regions. However, high uptake in bone was also observed. No blocking effect was detected during a competition experiment with a 5-HT 2A R selective antagonist. [ 18 F]2 and [ 18 F]3 showed very low brain uptake. Conclusion: None of the investigated 18 F-labeled Cimbi-36 derivatives [ 18 F]1, [ 18 F]2 and [ 18 F]3 show suitable tracer characteristics for in vivo PET neuroimaging of the 5-HT 2A R. Although for [ 18 F]1 there was reasonable brain uptake, we suggest that a large proportion radioactivity in the brain was due to radiometabolites, which would explain why it could not be displaced by a 5-HT 2A R antagonist.

  12. Selecting Safe Pets (For Parents)

    Science.gov (United States)

    ... supplies (pet bowls, pet bed, leash, etc.) as gifts, then selecting the pet as a family. That way, everyone has time to really think about whether your family is ready for a pet. Key Questions Before adopting or purchasing any pet, talk to all family members, discuss ...

  13. Pet-Related Infections.

    Science.gov (United States)

    Day, Michael J

    2016-11-15

    Physicians and veterinarians have many opportunities to partner in promoting the well-being of people and their pets, especially by addressing zoonotic diseases that may be transmitted between a pet and a human family member. Common cutaneous pet-acquired zoonoses are dermatophytosis (ringworm) and sarcoptic mange (scabies), which are both readily treated. Toxoplasmosis can be acquired from exposure to cat feces, but appropriate hygienic measures can minimize the risk to pregnant women. Persons who work with animals are at increased risk of acquiring bartonellosis (e.g., cat-scratch disease); control of cat fleas is essential to minimize the risk of these infections. People and their pets share a range of tick-borne diseases, and exposure risk can be minimized with use of tick repellent, prompt tick removal, and appropriate tick control measures for pets. Pets such as reptiles, amphibians, and backyard poultry pose a risk of transmitting Salmonella species and are becoming more popular. Personal hygiene after interacting with these pets is crucial to prevent Salmonella infections. Leptospirosis is more often acquired from wildlife than infected dogs, but at-risk dogs can be protected with vaccination. The clinical history in the primary care office should routinely include questions about pets and occupational or other exposure to pet animals. Control and prevention of zoonoses are best achieved by enhancing communication between physicians and veterinarians to ensure patients know the risks of and how to prevent zoonoses in themselves, their pets, and other people.

  14. Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Zerizer, Imene; Tan, Kathryn; Khan, Sameer; Barwick, Tara [Department of Nuclear Medicine, Imperial College Healthcare, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Marzola, Maria Cristina [Department of Nuclear Medicine, PET/CT Centre, Radiology and Medical Physics, ' Santa Maria della Misericordia' Hospital, Rovigo (Italy); Rubello, Domenico [Department of Nuclear Medicine, PET/CT Centre, Radiology and Medical Physics, ' Santa Maria della Misericordia' Hospital, Rovigo (Italy)], E-mail: domenico.rubello@libero.it; Al-Nahhas, Adil [Department of Nuclear Medicine, Imperial College Healthcare, Hammersmith Hospital, Du Cane Road, London (United Kingdom)

    2010-03-15

    Purpose: to investigate the role of FDG-PET and PET/CT in the evaluation of vasculitis. Materials and methods: a systematic revision of the papers published in PubMed/Medline until December 2009 was done. Results: FDG-PET and PET/CT have been proven to be valuable in the diagnosis of large-vessel vasculitis, especially giant cells arteritis with sensitivity values ranging 77% to 92%, and specificity values ranging 89% to 100%. In particular, FDG-PET/CT has demonstrated the potential to non-invasively diagnose the onset of the vasculitis earlier than traditional anatomical imaging techniques, thus enabling prompt treatment. False positive results mainly occur in the differential diagnosis between vasculitis and atherosclerotic vessels in elderly patients. Another area where FDG-PET/CT is gaining wider acceptance is in monitoring response to therapy; it can reliably detect the earliest changes of disease improvement post-therapy, and persistent activity is an indicator of non-responders to therapy. A few data have been reported about medium/small vessel vasculitis. Discussion: FDG-PET and PET/CT have proven utility: (a) in the initial diagnosis of patients suspected of having vasculitis particularly in those who present with non-specific symptoms; (b) in the identification of areas of increased FDG uptake in which a biopsy should be done for obtaining a diagnosis; (c) in evaluating the extent of the disease; (d) in assessing response to treatment.

  15. Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis

    International Nuclear Information System (INIS)

    Zerizer, Imene; Tan, Kathryn; Khan, Sameer; Barwick, Tara; Marzola, Maria Cristina; Rubello, Domenico; Al-Nahhas, Adil

    2010-01-01

    Purpose: to investigate the role of FDG-PET and PET/CT in the evaluation of vasculitis. Materials and methods: a systematic revision of the papers published in PubMed/Medline until December 2009 was done. Results: FDG-PET and PET/CT have been proven to be valuable in the diagnosis of large-vessel vasculitis, especially giant cells arteritis with sensitivity values ranging 77% to 92%, and specificity values ranging 89% to 100%. In particular, FDG-PET/CT has demonstrated the potential to non-invasively diagnose the onset of the vasculitis earlier than traditional anatomical imaging techniques, thus enabling prompt treatment. False positive results mainly occur in the differential diagnosis between vasculitis and atherosclerotic vessels in elderly patients. Another area where FDG-PET/CT is gaining wider acceptance is in monitoring response to therapy; it can reliably detect the earliest changes of disease improvement post-therapy, and persistent activity is an indicator of non-responders to therapy. A few data have been reported about medium/small vessel vasculitis. Discussion: FDG-PET and PET/CT have proven utility: (a) in the initial diagnosis of patients suspected of having vasculitis particularly in those who present with non-specific symptoms; (b) in the identification of areas of increased FDG uptake in which a biopsy should be done for obtaining a diagnosis; (c) in evaluating the extent of the disease; (d) in assessing response to treatment.

  16. Use of PET and PET/CT for Radiation Therapy Planning: IAEA expert report 2006-2007

    International Nuclear Information System (INIS)

    MacManus, Michael; Nestle, Ursula; Rosenzweig, Kenneth E.; Carrio, Ignasi; Messa, Cristina; Belohlavek, Otakar; Danna, Massimo; Inoue, Tomio; Deniaud-Alexandre, Elizabeth; Schipani, Stefano; Watanabe, Naoyuki; Dondi, Maurizio; Jeremic, Branislav

    2009-01-01

    Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants' meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, 18 F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

  17. Synthesis and evaluation of iodine-123 labelled tricyclic tropanes as radioligands for the serotonin transporter

    International Nuclear Information System (INIS)

    Quinlivan, Mitchell; Mattner, Filomena; Papazian, Vahan; Zhou, Jia; Katsifis, Andrew; Emond, Patrick; Chalon, Sylvie; Kozikowski, Alan; Guilloteau, Denis; Kassiou, Michael

    2003-01-01

    The tricyclic tropane analogues (1S,3S,6R,10S)-(Z)-10-(benzoyloxymethyl)-9-(3-chloro-4-iodobenzylidene)-7 -azatricyclo[4.3.1.0 3,7 ]decane, 1, and (1S,3S,6R,10S)-(Z)-9-(3-chloro-4-iodobenzylidene)-7-azatricyclo[4.3.1.0 3,7 ] = decane-10-carboxylic acid methyl ester, 2, have been shown to be potent and selective serotonin transporter (SERT) ligands. They possess nanomolar affinity for the SERT (Ki = 0.06 nM and 1.8 nM respectively) and are suitable for radiolabelling using iodine-123. In the present study we prepared [ 123 I]1 and [ 123 I]2 from the appropriate tributylstannane precursors using acidic media with chloramine-T as the oxidising agent. The radiochemical yield obtained for [ 123 I]1 varied between 50-60% while for [ 123 I]2 the range was 65-80%. Both radioligands were obtained with radiochemical purity > 97% and specific activity estimated to be > 185 GBq/μmol. The biodistribution of [ 123 I]1 demonstrated low degree of brain penetration at 5 min (0.14%ID/g) with a homogenous distribution. The radioactivity cleared quickly from all brain regions with no preferential localization. In comparison, [ 123 I]2 demonstrated on average a higher brain uptake at 5 min (0.5%ID/g). However the distribution of radioactivity was homogenous and cleared to levels similar to [ 123 I]1 at 1 hr post-injection. Pre-administration of citalopram failed to show any significant inhibition of [ 123 I]2 uptake in the rat brain. The high lipophilicity of 1 and 2 (HPLC-derived log P 7.4 values of 6.41 and 4.25 respectively) and in vivo metabolism, seen by high thyroid uptake would explain the absence of any specific binding observed in the rat brain. In view of these results [ 123 I]1 and [ 123 I]2 do not appear to be suitable radioligands for in vivo studies of the SERT

  18. Synthesis and evaluation of iodine-123 labelled tricyclic tropanes as radioligands for the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Quinlivan, Mitchell; Mattner, Filomena; Papazian, Vahan; Zhou, Jia; Katsifis, Andrew; Emond, Patrick; Chalon, Sylvie; Kozikowski, Alan; Guilloteau, Denis; Kassiou, Michael E-mail: mkassiou@med.usyd.edu.au

    2003-10-01

    The tricyclic tropane analogues (1S,3S,6R,10S)-(Z)-10-(benzoyloxymethyl)-9-(3-chloro-4-iodobenzylidene)-7 -azatricyclo[4.3.1.0{sup 3,7}]decane, 1, and (1S,3S,6R,10S)-(Z)-9-(3-chloro-4-iodobenzylidene)-7-azatricyclo[4.3.1.0{sup 3,7}] = decane-10-carboxylic acid methyl ester, 2, have been shown to be potent and selective serotonin transporter (SERT) ligands. They possess nanomolar affinity for the SERT (Ki = 0.06 nM and 1.8 nM respectively) and are suitable for radiolabelling using iodine-123. In the present study we prepared [{sup 123}I]1 and [{sup 123}I]2 from the appropriate tributylstannane precursors using acidic media with chloramine-T as the oxidising agent. The radiochemical yield obtained for [{sup 123}I]1 varied between 50-60% while for [{sup 123}I]2 the range was 65-80%. Both radioligands were obtained with radiochemical purity > 97% and specific activity estimated to be > 185 GBq/{mu}mol. The biodistribution of [{sup 123}I]1 demonstrated low degree of brain penetration at 5 min (0.14%ID/g) with a homogenous distribution. The radioactivity cleared quickly from all brain regions with no preferential localization. In comparison, [{sup 123}I]2 demonstrated on average a higher brain uptake at 5 min (0.5%ID/g). However the distribution of radioactivity was homogenous and cleared to levels similar to [{sup 123}I]1 at 1 hr post-injection. Pre-administration of citalopram failed to show any significant inhibition of [{sup 123}I]2 uptake in the rat brain. The high lipophilicity of 1 and 2 (HPLC-derived log P{sub 7.4} values of 6.41 and 4.25 respectively) and in vivo metabolism, seen by high thyroid uptake would explain the absence of any specific binding observed in the rat brain. In view of these results [{sup 123}I]1 and [{sup 123}I]2 do not appear to be suitable radioligands for in vivo studies of the SERT.

  19. Multi-technique hybrid imaging in PET/CT and PET/MR: what does the future hold?

    International Nuclear Information System (INIS)

    Galiza Barbosa, F. de; Delso, G.; Voert, E.E.G.W. ter; Huellner, M.W.; Herrmann, K.; Veit-Haibach, P.

    2016-01-01

    Integrated positron-emission tomography and computed tomography (PET/CT) is one of the most important imaging techniques to have emerged in oncological practice in the last decade. Hybrid imaging, in general, remains a rapidly growing field, not only in developing countries, but also in western industrialised healthcare systems. A great deal of technological development and research is focused on improving hybrid imaging technology further and introducing new techniques, e.g., integrated PET and magnetic resonance imaging (PET/MRI). Additionally, there are several new PET tracers on the horizon, which have the potential to broaden clinical applications in hybrid imaging for diagnosis as well as therapy. This article aims to highlight some of the major technical and clinical advances that are currently taking place in PET/CT and PET/MRI that will potentially maintain the position of hybrid techniques at the forefront of medical imaging technologies.

  20. A kinetic analysis of kappa-opioid agonist binding using the selective radioligand (/sup 3/H)U69593

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.A.; Hunter, J.C.; Hill, R.G.; Hughes, J.

    1989-07-01

    The interaction of the nonselective opioid ligand (3H)bremazocine and of the kappa-opioid (3H)U69593 with the kappa-receptor was investigated in guinea-pig cortical membranes. Each radioligand bound to a single population of high-affinity sites, although (3H)U69593 apparently recognised only 70% of those sites labelled by (3H)bremazocine. Naloxone and the kappa-selective ligands U69593 and PD117302 exhibited full inhibition of the binding of both radioligands. Kinetic analysis demonstrated biphasic rates of association and dissociation for both (3H)bremazocine and (3H)U69593. Detailed analysis of the binding of (3H)U69593 revealed that the fast rate of association was dependent on radioligand concentration, in contrast to the slow rate, which was independent of ligand concentration. Guanylyl-5'-imidodiphosphate (GppNHp) inhibited binding of (3H)U69593; saturation analysis demonstrated that the inhibitory effects of GppNHp resulted in a decrease in affinity without any significant change in binding capacity. GppNHp attenuated the formation of the slow component of (3H)U69593 binding, while accelerating the fast component. The data are consistent with the formation of a high-affinity complex between the kappa-receptor and a guanine nucleotide binding protein. Guanine nucleotides promote the dissociation of this ternary complex and the stabilisation of a lower-affinity state of the receptor.

  1. Comparison of two synthetic methods to obtain [18F] N-(2-aminoethyl)-5-fluoropyridine-2-carboxamide, a potential MAO-B imaging tracer for PET

    International Nuclear Information System (INIS)

    Beer, H.-F.; Haeberli, M.; Ametamey, S.; Schubiger, P.A.

    1995-01-01

    The compound Ro 19-6327, N-(2-aminoethyl)-5-chloropyridine-2-carboxamide, is known to inhibit reversibly and site specifically the enzyme monoamine oxidase B (MAO-B). The 123 I-labelled iodo-analogue N-(2-aminoethyl)-5-iodopyridine-2-carboxamide (Ro 43-0463) was investigated successfully in human volunteers by means of SPET (Single Photon Emission Tomography). We developed therefore the synthesis and radiolabelling of the corresponding fluoro-analogue N-(2-aminoethyl)-5-fluoropyridine-2-carboxamide with 18 F in order to carry out PET (Positron Emission Tomography) investigations of MAO-B related neuropsychiatric diseases. For this purpose two synthetic approaches leading to the electrophilic and the nucleophilic methods of 18 F radiolabelling were undertaken. The nucleophilic approach appeared to be superior when factors such as precursor synthesis, beam time, specific activity and radiochemical purity of the product are considered. (author)

  2. Biodistribution and radiation dosimetry of 18F-CP-18, a potential apoptosis imaging agent, as determined from PET/CT scans in healthy volunteers.

    Science.gov (United States)

    Doss, Mohan; Kolb, Hartmuth C; Walsh, Joseph C; Mocharla, Vani; Fan, Hong; Chaudhary, Ashok; Zhu, Zhihong; Alpaugh, R Katherine; Lango, Miriam N; Yu, Jian Q

    2013-12-01

    (18)F-CP-18, or (18S,21S,24S,27S,30S)-27-(2-carboxyethyl)-21-(carboxymethyl)-30-((2S,3R,4R,5R,6S)-6-((2-(4-(3-F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)-24-isopropyl-18-methyl-17,20,23,26,29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioic acid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from (18)F-CP-18. Successive whole-body PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of (18)F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of (18)F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. (18)F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high (18)F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 ± 4 μSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 ± 61 μGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 ± 2 μSv/MBq and 142 ± 15 μGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 ± 2.2 mSv for the 4.8-h interval, reduced to 8.3 ± 1.1 mSv for the 1-h interval

  3. Pets and the immunocompromised person

    Science.gov (United States)

    ... marrow transplant patients and pets; Chemotherapy patients and pets ... Centers for Disease Control and Prevention website. Healthy pets healthy people. www.cdc.gov/healthypets . Updated July 19, 2016. ...

  4. Sensory analysis of pet foods.

    Science.gov (United States)

    Koppel, Kadri

    2014-08-01

    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities. © 2014 Society of Chemical Industry.

  5. PET in management of breast cancer

    International Nuclear Information System (INIS)

    Lee, Myung-Chul

    2004-01-01

    Full text: PET provides useful information about tumor metabolism enabling accurate visualization of malignant lesions. Approximately 60-80% suspicious lesions on mammography have benign histology and about 10% of breast cancers with palpable mass are not identified in mammography. The key roles of PET technology in breast cancer are in: primary diagnosis, staging, recurrent diseases monitoring and prediction of therapy response. The sensitivity and specificity of FDG-PET for the diagnosis of breast cancer has been reported to be 68-100% and 83-100%, respectively. Considering the increasing number of small breast tumors detected by mammography and false negative results, the clinical relevance of FDG-PET for the primary diagnosis is limited. In selected patients, however, for example with dense breasts, breasts implants, augmented breast or after breast surgery, which can affect the accuracy of mammography, and in cases with equivocal mammography, FDG-PET can provide clinically relevant information. PET accurately determines the extent of disease, including the loco-regional lymph node status. Furthermore, whole-body PET imaging promises a high diagnostic accuracy for detecting recurrent or metastatic breast carcinoma with a high positive predictive value. We studied the usefulness of the FDG-PET in 42 preoperative patients with suspected breast cancer in differentiation of lesions. The diagnostic value of FDG-PET in terms of sensitivity and specificity was 95% and 77% respectively in primary mass while it was 73% and 100% for axillary lymph nodes. PET is much more accurate than other conventional modalities. The sensitivity of FDG-PET for correct staging of axillary nodal status is 84-100%. It has the potential to replace conventional procedures for the staging of distant metastases. We observed the sensitivity and the specificity of FDG-PET to be 96% and 85% to detect distant metastases. FDG-PET may become the method of choice for the early assessment of

  6. Bacterial Zoonoses Transmitted by Household Pets

    DEFF Research Database (Denmark)

    Damborg, Peter Panduro; Broens, E.M.; Chomel, B.B.

    2016-01-01

    The close contact between household pets and people offers favourable conditions for bacterial transmission. In this article, the aetiology, prevalence, transmission, impact on human health and preventative measures are summarized for selected bacterial zoonoses transmissible by household pets. Six...... zoonoses representing distinct transmission routes were selected arbitrarily based on the available information on incidence and severity of pet-associated disease caused by zoonotic bacteria: bite infections and cat scratch disease (physical injuries), psittacosis (inhalation), leptospirosis (contact...... with urine), and campylobacteriosis and salmonellosis (faecal–oral ingestion). Antimicrobial resistance was also included due to the recent emergence of multidrug-resistant bacteria of zoonotic potential in dogs and cats. There is a general lack of data on pathogen prevalence in the relevant pet population...

  7. Clinical PET application

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Hong, Song W.; Choi, Chang W.; Yang, Seong Dae [Korea Cancer Center Hospital, Seoul (Korea)

    1997-12-01

    PET gives various methabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 250 cases of PET images were obtained, which resulted total income of 180,000,000 won. 50,000,000 won was deposited for the 1998 PET clinical research. Second year PET clinical research should be managed under unified project. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18}FDG in a day purchase of HPLC pump and {sup 68}Ga pin source which was delayed due to economic crisis, should be done early in 1998. (author). 2 figs., 3 tabs.

  8. Imaging with PET system

    International Nuclear Information System (INIS)

    Das, B.K.; Noreen Norfaraheen Lee Abdullah

    2012-01-01

    PET deals with biochemistry and metabolic changes that occur at molecular level. Hence, PET differs fundamentally from other imaging modalities. CT imaging is based on tissue density, whereas MRI conveys anatomic information based on proton density and proton relaxation dynamics. CT and MRI are useful in clinical diagnosis only when disease process has caused significant anatomic alterations. However, in most disease conditions chemical changes precede anatomic changes, that can be detected by PET technology. Thus, PET can provide earliest and unique information about ongoing disease process long before anatomic or structural changes take place. There is no other modality available at present that can replace PET technology. Although PET produces cross-sectional images like that obtained in MRI or CT, they represent circulation, function and metabolism, and not anatomic structure. PET is extremely sensitive measuring quantitatively concentration of tracers in nano to pico-molar range. Thus, PET enables merger of biochemistry and biology in medicine giving birth to molecular medicine that focuses on identifying the molecular errors of disease leading to developing molecular corrections including gene therapy. Molecular imaging with PET has been playing a role in examining the biological nature of a disease condition and its characterization to guide selection and evaluation of treatment. (author)

  9. The Z-isomer of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol is a promising radioligand for estrogen receptor imaging in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rijks, Leonie J. M.; Boer, Gerard J.; Endert, Erik; Bruin, Kora de; Janssen, Anton G. M.; Royen, Eric A. van

    1997-01-01

    The potential of both stereoisomers of 11{beta}-methoxy-17{alpha}-[{sup 123}I]iodovinylestradiol (E- and Z-[{sup 123}I]MIVE) as suitable radioligands for imaging of estrogen receptor(ER)-positive human breast tumours was studied. The 17{alpha}-[{sup 123}I]iodovinylestradiol derivatives were prepared stereospecifically by oxidative radioiododestannylation of the corresponding 17{alpha}-tri-n-butylstannylvinylestradiol precursors. Both isomers of MIVE showed high in vitro affinity for dimethylbenzanthracene-induced rat and fresh human mammary tumour ER, that of Z-MIVE however being manyfold higher than that of E-MIVE. In vivo distribution studies with E- and Z-[{sup 123}I]MIVE in normal and tumour-bearing female rats showed ER-mediated uptake and retention in uterus, ovaries, pituitary, hypothalamus and mammary tumours, again the highest for Z-[{sup 123}I]MIVE. The uterus- and tumour-to-nontarget tissue (fat, muscle) uptake ratios were also highest for Z-[{sup 123}I]MIVE. Additionally, planar whole body imaging of two breast cancer patients 1-2 h after injection of Z-[{sup 123}I]MIVE showed increased focal uptake at known tumour sites. Therefore, we conclude that Z-[{sup 123}I]MIVE is a promising radioligand for the diagnostic imaging of ER in human breast cancer.

  10. [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.)

  11. Direct 125I-radioligand assays for serum progesterone compared with assays involving extraction of serum

    International Nuclear Information System (INIS)

    Ratcliffe, W.A.; Corrie, J.E.T.; Dalziel, A.H.; Macpherson, J.S.

    1982-01-01

    Two direct radioimmunoassays for progesterone in 50 μL of unextracted serum or plasma with assays involving extraction of serum were compared. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11α-hemisuccinyl conjugate and the radioligand 125 I-labeled progesterone 11α-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r > 0.96) with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum

  12. A comparative study in three commercial kits of radioligand assay for GAD-Ab

    International Nuclear Information System (INIS)

    Yang Yehua; Zhou Zhiguang; Huang Gan; Yang Feike; Li Zhangwei

    2006-01-01

    Objective: To provide data for perfect selection of glutamic acid decarboxylase antibodies (GAD-Ab) assay commercial kits. Methods: The sera of 88 titer-graded samples by radioligand assay (RLA) were measured with two types of enzyme-linked immunosorbent assay (ELISA) kits and one type of immunoradiometric assay (IRMA) kit for GAD-Ab in order to test their consistency with RLA. Another 140 diabetic sera were measured with RLA and screened by a type of suitable kit to search the cutoff point for discriminating patients who needed rechecking. Results: Compared with RLA, concordance ratio of 3 kits: Medizym kit(75%) > RSR kit(73.9%) > Biomerica kit(62.5%); Kappa value: Medizym kit (0.408, common) > RSR kit (0.405, common) > Biomerica kit (0.185, failing); correlation to RLA index: RSR kit (r= 0.992) > Medizym kit(r= 0. 791 ) > Biomerica kit (r = -0. 055); area under the receiver operating characteristic (ROC) curve: Medizym kit (0.812) > RSR kit (0. 727 ) > Biomerica kit (0.666). Conclusions: The efficiencies of RSR kit and Medizym kit are good. Serum concentration between 0.25-0.99 U/ml measured by RSR kit is suggested to further recheck by RLA. (authors)

  13. Determination of luteinizing hormone in bovine blood by radioligand receptor assay and comparison with radioimmunological evaluation

    International Nuclear Information System (INIS)

    Schams, D.; Menzer, C.

    1978-01-01

    A sensitive and specific radioligand receptor assay (RRA) using rat testis homogenate as the receptor source is described for measurement of luteinizing hormone (LH) in bovine blood. Interfering and nonspecific substances in blood were removed by means of ion-exchange chromatography on CM-Sephadex C-50. Criteria of validation such as recovery of added LH to plasma or serum, reproducibility, and specificity gave good results. Inhibition curves obtained with bovine plasma and serum were parallel to those obtained with the bovine standard preparation. The range of the dose-response curve was between 0.5-20 ng of bovine LH. The pattern of LH concentrations in purified serum samples under different physiological conditions such as during the oestrous cycle and after administration of GnRH showed a very close correlattion whether measured by means of radioimmunoassay (RIA) or receptor assay. Values of RRA-LH were consistently higher than those of RIA-LH. Thus the lower the RIA-LH levels, the more pronounced were the discrepancies between results of both assay systems. The mean ratio of RRA-LH/RIA-LH for basal levels (less than 1 ng RIA-LH/ml plasma) was 17.8 as compared to a mean ratio for higher peak values (more than 20 ng RIA-LH/ml plasma) of only 1.2. (author)

  14. New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors

    Directory of Open Access Journals (Sweden)

    Olivier Nosjean

    2013-04-01

    Full Text Available Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[125I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and S70254. These compounds were characterized for their affinities to the hMT1 and hMT2 recombinant receptors and their functionality in the classical GTPS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas S70254 and DIV880 are only partial MT2 agonists, with Ki in the low nanomolar range while they have no affinity to MT1 receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues.

  15. Elaboration of a radioligand receptor assay for TSH and thyroid-stimulating immunoglobulins

    International Nuclear Information System (INIS)

    Wille, A.

    1980-01-01

    125 J-TSH is bound by membrane preparations from human thyroid glands. The removal of the radioactive hormone from the bond, interpreted by means of a standard curve, is an indicator of the unknown quantity of TSH or TSI. The specific binding of the TSH to the membrane proceeds as a function of hydrogen ion concentration, temperature, and incubation time. Since all globulins exhibit an unspecific binding to the membranes, it is necessary to separate the gamma globulin fraction from the serum in order to detect the TSI. The separation is achieved by QAE Sephadex A-50 columns. The displacement characteristics of the gamma globulin fractions are determined in the radioligand receptor assay. The classification into normal and pathological findings is done in accordance with the TSI index of Smith and Hall. The poor detection of TSI in the sera studied is attributed to the fact that the group of patients of this study had already been treated at the time the blood sera were taken. The TSH content of homogenates from human, postmortally taken pituitary glands is determined by the RRA and compared with the TSH values of the RIA. The comparison shows a positive correlation, with the TSH data of the RRA being above those of the radioimmunoassay. (orig./MG) [de