title: Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain.
abstract: The purpose of this study was to synthesize 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline ([(18)F]FPTQ, [(18)F]7a) and to evaluate its potential as a positron emission tomography ligand for imaging metabotropic glutamate receptor type 1 (mGluR1) in the rat brain. Compound [(18)F]7a was synthesized by [(18)F]fluorination of 6-[1-(2-bromo-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline (7b) with potassium [(18)F]fluoride. At the end of synthesis, 1280-1830MBq (n=8) of [(18)F]7a was obtained with >98% radiochemical purity and 118-237GBq/μmol specific activity using 3300-4000MBq of [(18)F]F(-). In vitro autoradiography showed that [(18)F]7a had high specific binding with mGluR1 in the rat brain. Biodistribution study using a dissection method and small-animal PET showed that [(18)F]7a had high uptake in the rat brain. The uptake of radioactivity in the cerebellum was reduced by unlabeled 7a and mGluR1-selective ligand JNJ-16259685 (2), indicating that [(18)F]7a had in vivo specific binding with mGluR1. Because of a low amount of radiolabeled metabolite present in the brain, [(18)F]7a may have a limiting potential for the in vivo imaging of mGluR1 by PET.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nengaki
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D011804:Quinolines / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014018:Tissue Distribution; D014230:Triazoles / Q000378:metabolism*
chemical_list: C557985:6-(1-(2-fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl)quinoline; D011804:Quinolines; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D014230:Triazoles; C104077:metabotropic glutamate receptor type 1