2. Academic Validation
  3. 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)

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

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.

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