title: Radiosynthesis and preliminary PET evaluation of (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors.
abstract: To prompt the development of (18)F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared (18)F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1,2-dihydropyridin-3-yl)benzonitrile ([(18)F]8). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the (18)F-labeled 1-bromo-3-fluorobenzene ([(18)F]15) intermediate with K(18)F. 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 [(18)F]8 in 10±2% uncorrected radiochemical yield relative to starting (18)F-fluoride with >99% radiochemical purity and 29.6±7.4Gbq/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.
authors.affiliation: Department of Chemistry & Chemical Biology, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA; Gordon Center for Medical Imaging & Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA.
authors.forename: Gengyang
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Chemistry & Chemical Biology, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA.
authors.forename: Graham B
authors.initials: GB
authors.lastname: Jones
authors.affiliation: Gordon Center for Medical Imaging & Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA. Electronic address: vasdev.neil@mgh.harvard.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
authors.affiliation: Gordon Center for Medical Imaging & Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School, 55 Fruit St., Boston, MA 02114, USA. Electronic address: liang.steven@mgh.harvard.edu.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000008:administration & dosage*; D051379:Mice; D049268:Positron-Emission Tomography; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D018091:Receptors, AMPA
keywords: AMPA receptor; Fluorine-18; Perampanel; Positron emission tomography; Radiotracer