Synthesis and in vitro evaluation of three novel radiotracers for imaging of metabotropic glutamate receptor subtype 2 in rat brain. Issue 14 (15th July 2017)

• Record Type: Journal Article
• Authors: Kumata, Katsushi; Yamasaki, Tomoteru; Hatori, Akiko; Zhang, Yiding; Mori, Wakana; Fujinaga, Masayuki; Xie, Lin; Okubo, Takayuki; Nengaki, Nobuki; Zhang, Ming-Rong
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 14(2017)
• Page Start: 3139
• Page End: 3143
• Publication Date: 2017-07-15
• Subjects: In vitro autoradiography -- Metabotropic glutamate receptor 2 -- Positron emission tomography -- Radiotracer -- Schizophrenia; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.05.029
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The purpose of this study was to develop three new radiotracers, 1-(cyclopropylmethyl)-4-([ 11 C/ 18 F]substituted-phenyl)piperidin-1-yl-2-oxo-1, 2-dihydropyridine-3-carbonitrile ([ 11 C]1, [ 11 C]2, and [ 18 F]4 ), and to examine their specific bindings with metabotropic glutamate receptor subtype 2 (mGluR2) in rat brain sections by using in vitro autoradiography. These compounds were found to possess potent in vitro binding affinities ( K i : 8.0–34.1 nM) for mGluR2 in rat brain homogenate. [ 11 C]1, [ 11 C]2, and [ 18 F]4 were synthesized by [ 11 C/ 18 F]alkylation of the corresponding phenol precursors with [ 11 C]methyl iodide or [ 18 F]fluoroethyl bromide with >98% radiochemical purity and 80–130 GBq/μmol specific activity at the end of synthesis. In vitro autoradiography indicated that these radiotracers showed heterogeneous specific bindings in mGluR2-rich brain regions, such as the cerebral cortex, striatum, hippocampus, and granular layer of the cerebellum.