title: Synthesis and in vitro evaluation of [18F](R)-FEPAQ: a potential PET ligand for VEGFR2.
abstract: 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.
authors: Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA. jp2155@columbia.edu
authors: Jaya
authors: J
authors: Prabhakaran
authors: Victoria
authors: V
authors: Arango
authors: Vattoly J
authors: VJ
authors: Majo
authors: Norman R
authors: NR
authors: Simpson
authors: Suham A
authors: SA
authors: Kassir
authors: Mark D
authors: MD
authors: Underwood
authors: Hanish
authors: H
authors: Polavarapu
authors: Jeffrey N
authors: JN
authors: Bruce
authors: Peter
authors: P
authors: Canoll
authors: J John
authors: JJ
authors: Mann
authors: J S Dileep
authors: JS
authors: Kumar
mesh_terms: D001921:Brain / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005462:Fluorine Radioisotopes / Q000737:chemistry; D005910:Glioma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005462:Fluorine Radioisotopes; D008024:Ligands; C576466:N-(4-bromo-2-fluorophenyl)-7-((1-(2-fluoroethyl)piperidin-3-yl)methoxy)-6-methoxyquinazolin-4-amine; D011799:Quinazolines; D019275:Radiopharmaceuticals; D040301:Vascular Endothelial Growth Factor Receptor-2