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

Autor: Kumata K; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Yamasaki T; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Hatori A; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Zhang Y; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Mori W; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Fujinaga M; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Xie L; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan., Okubo T; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; SHI Accelerator Services Co., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan., Nengaki N; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan; SHI Accelerator Services Co., 1-17-6 Osaki, Shinagawa-ku, Tokyo 141-0032, Japan., Zhang MR; Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan. Electronic address: zhang.ming-rong@qst.go.jp.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Jul 15; Vol. 27 (14), pp. 3139-3143. Date of Electronic Publication: 2017 May 23.
DOI: 10.1016/j.bmcl.2017.05.029
Abstrakt: 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 : 8.0-34.1nM) 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 80-130GBq/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.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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