Radiosynthesis and preliminary PET evaluation of 18F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors

To prompt the development of F-18-labeled positron emission tomography (PET) tracers for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared F-18-labeled 2-(1-(3fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl) benzonitrile ([F-18] 8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the F-18-labeled 1-bromo-3-fluorobenzene ([F-18] 15) intermediate with (KF)-F-18. 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 [F-18] 8 in 10 +/- 2% uncorrected radiochemical yield relative to starting F-18-fluoride with > 99% radiochemical purity and 29.6 +/- 7.4 Gbq/lmol 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. (C) 2016 Elsevier Ltd. All rights reserved.