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)

  • Bioorg Med Chem Lett. 2016 Jan 15;26(2):370-374. doi: 10.1016/j.bmcl.2015.12.008.
Masayuki Fujinaga  1 ,  Tomoteru Yamasaki  1 ,  Nobuki Nengaki  2 ,  Masanao Ogawa  2 ,  Katsushi Kumata  1 ,  Yoko Shimoda  1 ,  Joji Yui  1 ,  Lin Xie  1 ,  Yiding Zhang  1 ,  Kazunori Kawamura  1 ,  Ming-Rong Zhang  3
Affiliations
  • 1. Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
  • 2. 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.
  • 3. Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: [email protected].
PMID: 26707390 DOI: 10.1016/j.bmcl.2015.12.008
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.

Keywords
Autoradiography; PET; [(11)C]ADX88178; mGluR4.