Synthesis and in vitro evaluation of [18F](R)-FEPAQ: a potential PET ligand for VEGFR2

Synthesis and in vitro evaluation of (18)F](R)-N-(4-bromo-2-fluorophenyl)-7-((1-(2-fluoroethyl)piperidin-3-yl)methoxy)-6-methoxyquinazolin-4-amine ((R)-(18)F]FEPAQ or (18)F]1), a potential imaging agent for the VEGFR2, using phosphor image autoradiography are described. Synthesis of 2, the desfluoroethyl precursor for (R)-FEPAQ was achieved from t-butyl 3-(hydroxymethyl)piperidine-1-carboxylate (3) in five steps and in 50% yield. (18)F]1 was synthesized by reaction of sodium salt of compound 2 with (18)F]fluoroethyl tosylate in DMSO. The yield of (18)F]1 was 20% (EOS based on (18)F]F(-)) with >99% radiochemical purity and specific activity of 1-2 Ci/μmol (n=10). The total synthesis time was 75 min. The radiotracer selectively labeled VEGFR2 in slide-mounted sections of human brain and higher binding was found in surgically removed human glioblastoma sections as demonstrated by in vitro phosphor imager studies. These findings suggest (18)F]1 may be a promising radiotracer for imaging VEGFR2 in brain using PET.