title: 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.
abstract: The purpose of this study was to develop 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM, [(18)F]4) as a new PET ligand for imaging metabotropic glutamate receptor subtype 1 (mGluR1). [(18)F]4 was synthesized by [(18)F]fluorination of a novel nitro precursor 3 with [(18)F]KF in the presence of Kryptofix 222. At the end of synthesis, 429-936 MBq (n=8) of [(18)F]4 was obtained with >99% radiochemical purity and 204-559GBq/μmol specific activity starting from 6.7 to 13.0 GBq of [(18)F]F(-). The brain distribution of [(18)F]4 was determined by the in vitro and ex vivo autoradiography using rat brain sections. The in vitro and in vivo specific binding of [(18)F]4 to mGluR1 was detected in the cerebellum, thalamus, hippocampus, and striatum. These results suggest that [(18)F]4 is a promising PET ligand for the in vivo evaluation of mGluR1.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba 263-8555, Japan.
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000032:analysis / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: C560416:4-fluoro-N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N-methylbenzamide; D001549:Benzamides; D008024:Ligands; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1