Add time:09/04/2019 Source:sciencedirect.com
To prompt the development of 18F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared 18F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([18F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the 18F-labeled 1-bromo-3-fluorobenzene ([18F]15) intermediate with K18F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile (10) to [18F]8 in 10 ± 2% uncorrected radiochemical yield relative to starting 18F-fluoride with >99% radiochemical purity and 29.6 ± 7.4 Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV) = 2.3 ± 0.1) and warrants further in vivo validation.
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