Synthesis and in vitro evaluation of three novel radiotracers for imaging of metabotropic glutamate receptor subtype 2 in rat brain

• Published in: Bioorganic & medicinal chemistry letters 2017-07, Vol.27 (14), p.3139-3143
• Main Authors: Kumata, Katsushi, Yamasaki, Tomoteru, Hatori, Akiko, Zhang, Yiding, Mori, Wakana, Fujinaga, Masayuki, Xie, Lin, Okubo, Takayuki, Nengaki, Nobuki, Zhang, Ming-Rong
• Format: Article
• Language: English
• Subjects: Animals; Autoradiography; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes - chemistry; Fluorine Radioisotopes - chemistry; In vitro autoradiography; Isotope Labeling; Kinetics; Metabotropic glutamate receptor 2; Positron emission tomography; Protein Binding; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Radiotracer; Rats; Receptors, Metabotropic Glutamate - metabolism; Schizophrenia; Signal-To-Noise Ratio
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.05.029

[Display omitted] The purpose of this study was to develop three new radiotracers, 1-(cyclopropylmethyl)-4-([11C/18F]substituted-phenyl)piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([11C]1, [11C]2, and [18F]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 (Ki: 8.0–34.1nM) for mGluR2 in rat brain homogenate. [11C]1, [11C]2, and [18F]4 were synthesized by [11C/18F]alkylation of the corresponding phenol precursors with [11C]methyl iodide or [18F]fluoroethyl bromide with >98% radiochemical purity and 80–130GBq/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.