Radiosynthesis and preliminary evaluation of 4-[ 18F]fluoro- N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]- N-methylbenzamide as a new positron emission tomography ligand for metabotropic glutamate receptor subtype 1

• Published in: Bioorganic & medicinal chemistry letters 2011-05, Vol.21 (10), p.2998-3001
• Main Authors: Yamasaki, Tomoteru, Fujinaga, Masayuki, Yoshida, Yuichiro, Kumata, Katsushi, Yui, Joji, Kawamura, Kazunori, Hatori, Akiko, Fukumura, Toshimitsu, Zhang, Ming-Rong
• Format: Article
• Language: English
• Subjects: Animals; autoradiography; Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - metabolism; Biological and medical sciences; Brain - metabolism; cerebellum; Contrast media. Radiopharmaceuticals; fluorine; glutamic acid; hippocampus; image analysis; in vivo studies; Inhibitory Concentration 50; Ligands; Medical sciences; mGluR1; Molecular Structure; PET; Pharmacology. Drug treatments; positron-emission tomography; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - metabolism; Rats; Receptors, Metabotropic Glutamate - analysis; Receptors, Metabotropic Glutamate - metabolism; thalamus; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.03.046

The purpose of this study was to develop 4-[ 18F]fluoro- N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]- N-methylbenzamide ([ 18F]FITM, [ 18F] 4) as a new PET ligand for imaging metabotropic glutamate receptor subtype 1 (mGluR1). [ 18F] 4 was synthesized by [ 18F]fluorination of a novel nitro precursor 3 with [ 18F]KF in the presence of Kryptofix 222. At the end of synthesis, 429–936 MBq ( n = 8) of [ 18F] 4 was obtained with >99% radiochemical purity and 204–559 GBq/μmol specific activity starting from 6.7 to 13.0 GBq of [ 18F]F −. The brain distribution of [ 18F] 4 was determined by the in vitro and ex vivo autoradiography using rat brain sections. The in vitro and in vivo specific binding of [ 18F] 4 to mGluR1 was detected in the cerebellum, thalamus, hippocampus, and striatum. These results suggest that [ 18F] 4 is a promising PET ligand for the in vivo evaluation of mGluR1.