title: Radiosynthesis and evaluation of 5-methyl-N-(4-[(11)C]methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine ([(11)C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4).
abstract: ADX88178 (1) has been recently developed as a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4). The aim of this study was to develop [(11)C]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [(11)C]1 was efficiently synthesized by introducing an [(11)C]methyl group into a pyrimidine ring via C-(11)C coupling and deprotection reactions, in 16±6% radiochemical yield (n=10). At the end of synthesis, 0.54-1.10GBq of [(11)C]1 was acquired with >98% radiochemical purity and 90-120GBq/μmol of specific activity. In vitro autoradiography and ex vivo biodistribution study in rat brains showed specific binding of [(11)C]1 in the cerebellum, striatum, thalamus, cerebral cortex, and medulla oblongata, which showed dose-dependent decreases by administration with multi-dose of unlabeled 1.
authors.affiliation: Molecular Probe Program, 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.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; SHI Accelerator Service Co. Ltd, 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nengaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; SHI Accelerator Service Co. Ltd, 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: zhang@nirs.go.jp.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000378:metabolism*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C000591920:5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C108823:metabotropic glutamate receptor 4
keywords: Autoradiography; PET; [(11)C]ADX88178; mGluR4