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• W4318244605 abstract "Abstract GluN2B subunit-containing N- methyl-d-aspartate (NMDA) receptors have been implicated in various neurological disorders. Nonetheless, a validated fluorine-18 labeled positron emission tomography (PET) ligand for GluN2B imaging in the living human brain is currently lacking. As part of our PET ligand development program, we have recently reported on the preclinical evaluation of [ 18 F]OF-NB1 – a GluN2B PET ligand with promising attributes for potential clinical translation. However, the further development of [ 18 F]OF-NB1 is currently precluded by major limitations in the radiolabeling procedure. These limitations include the use of highly corrosive reactants and racemization during the radiosynthesis. As such, the aim of this study was to develop a synthetic approach that allows an enantiomerically pure radiosynthesis of ( R ) - [ 18 F]OF-NB1 and ( S ) - [ 18 F]OF-NB1, as well as to assess their in vitro and in vivo performance characteristics for imaging the GluN2B subunit-containing NMDA receptor in rodents. A two-step radiosynthesis involving radiofluorination of the boronic acid pinacol ester, followed by coupling to the 3-benzazepine core structure via reductive amination was employed. The new synthetic approach yielded enantiomerically pure ( R ) - [ 18 F]OF-NB1 and ( S ) - [ 18 F]OF-NB1, while concurrently circumventing the use of corrosive reactants. In vitro autoradiograms with mouse and rat brain sections revealed a higher selectivity of ( R ) - [ 18 F]OF-NB1 over ( S ) - [ 18 F]OF-NB1 for GluN2B-rich brain regions. In concert with these observations, blockade studies with commercially available GluN2B antagonist, CP101606, showed a significant signal reduction, which was more pronounced for ( R ) - [ 18 F]OF-NB1 than for ( S ) - [ 18 F]OF-NB1. Conversely, blockade experiments with sigma2 ligand, FA10, did not result in a significant reduction of tracer binding for both enantiomers. PET imaging experiments with CD1 mice revealed a higher brain uptake and retention for ( R ) - [ 18 F]OF-NB1, as assessed by visual inspection and volumes of distribution from Logan graphical analyses. In vivo blocking experiments with sigma2 ligand, FA10, did not result in a significant reduction of the brain signal for both enantiomers, thus corroborating the selectivity over sigma2 receptors. In conclusion, we have developed a novel synthetic approach that is suitable for upscale to human use and allows the enantiomerically pure radiosynthesis of ( R ) - [ 18 F]OF-NB1 and ( S ) - [ 18 F]OF-NB1. While both enantiomers were selective over sigma2 receptors in vitro and in vivo , ( R ) - [ 18 F]OF-NB1 showed superior GluN2B subunit specificity by in vitro autoradiography and higher volumes of distribution in small animal PET studies." @default.
• W4318244605 created "2023-01-27" @default.
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• W4318244605 date "2023-01-27" @default.
• W4318244605 modified "2023-09-24" @default.
• W4318244605 title "Synthesis and Biological Evaluation of Enantiomerically Pure (R)- and (S)-[18F]OF-NB1 for Imaging the GluN2B Subunit-Containing NMDA receptors" @default.
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• W4318244605 cites W1965413171 @default.
• W4318244605 cites W1966363887 @default.
• W4318244605 cites W1969262850 @default.
• W4318244605 cites W1975138972 @default.
• W4318244605 cites W1980311878 @default.
• W4318244605 cites W1981502499 @default.
• W4318244605 cites W1997568797 @default.
• W4318244605 cites W1998347917 @default.
• W4318244605 cites W2000599697 @default.
• W4318244605 cites W2005766376 @default.
• W4318244605 cites W2012641732 @default.
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• W4318244605 cites W2024380057 @default.
• W4318244605 cites W2034961929 @default.
• W4318244605 cites W2037852973 @default.
• W4318244605 cites W2041024256 @default.
• W4318244605 cites W2053365908 @default.
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• W4318244605 cites W2085912953 @default.
• W4318244605 cites W2089417717 @default.
• W4318244605 cites W2095159395 @default.
• W4318244605 cites W2113944645 @default.
• W4318244605 cites W2116531960 @default.
• W4318244605 cites W2139976683 @default.
• W4318244605 cites W2143873033 @default.
• W4318244605 cites W2145547868 @default.
• W4318244605 cites W2157232476 @default.
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• W4318244605 cites W2324736404 @default.
• W4318244605 cites W2426802935 @default.
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• W4318244605 cites W2793783600 @default.
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• W4318244605 cites W2810762414 @default.
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• W4318244605 doi "https://doi.org/10.21203/rs.3.rs-2516002/v1" @default.
• W4318244605 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36747738" @default.
• W4318244605 hasPublicationYear "2023" @default.
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