Radiosynthesis and evaluation of 5-methyl-N-(4-[¹¹C]methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine ([¹¹C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4)

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• 作者：Masayuki Fujinaga^a ; ^&dagger ; ; Tomoteru Yamasaki^a ; ^&dagger ; ; Nobuki Nengaki^a ; ^b ; Masanao Ogawa^a ; ^b ; Katsushi Kumata^a ; Yoko Shimoda^a ; Joji Yui^a ; Lin Xie^a ; Yiding Zhang^a ; Kazunori Kawamura^a ; Ming-Rong Zhang^a ; ^{zhang@nirs.go.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：mGluR4 ; PET ; Autoradiography ; [11C]ADX88178
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：26
• 期：2
• 页码：370-374
• 全文大小：824 K

文摘

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 [¹¹C]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [¹¹C]1 was efficiently synthesized by introducing an [¹¹C]methyl group into a pyrimidine ring via C–¹¹C coupling and deprotection reactions, in 16 ± 6% radiochemical yield (n = 10). At the end of synthesis, 0.54–1.10 GBq of [¹¹C]1 was acquired with >98% radiochemical purity and 90–120 GBq/μmol of specific activity. In vitro autoradiography and ex vivo biodistribution study in rat brains showed specific binding of [¹¹C]1 in the cerebellum, striatum, thalamus, cerebral cortex, and medulla oblongata, which showed dose-dependent decreases by administration with multi-dose of unlabeled 1.