title: Radiosynthesis and preliminary PET evaluation of glycogen synthase kinase 3β (GSK-3β) inhibitors containing [(11)C]methylsulfanyl, [(11)C]methylsulfinyl or [(11)C]methylsulfonyl groups.
abstract: Three compounds 1-3 containing methyl-sufanyl, sufinyl, or sulfonyl groups are strong inhibitors of glycogen synthase kinase 3β (GSK-3β), an enzyme associated with Alzheimer's disease. We labeled 1-3 with (11)C for a positron emission tomography (PET) brain imaging study. A novel thiophenol precursor 4 for radiosynthesis was prepared by reacting sulfoxide 2 with trifluoroacetic anhydride. [(11)C]1 was synthesized by reacting 4 with [(11)C]methyl iodide in 52 ± 5% radiochemical yield (n = 5, based on [(11)C]CO2, corrected for decay). Oxidation of [(11)C]1 with Oxone® produced [(11)C]2 and [(11)C]3, respectively. PET with [(11)C]1 and [(11)C]3 showed 2 fold higher brain uptake of radioactivity in a mouse model of cold water stress in which GSK-3β expression was increased, than in the controls.
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yiding
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan; SHI Accelerator Service Co. Ltd, 5-9-11 Kitashinagawa, Shinagawa-ku, Tokyo 141-8686, Japan.
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nengaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimoda
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: zhang@nirs.go.jp.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D007202:Indicators and Reagents; D007553:Isotope Labeling; D051379:Mice; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000201:enzymology; D013464:Sulfuric Acids / Q000737:chemistry
chemical_list: D002250:Carbon Radioisotopes; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D013464:Sulfuric Acids; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C048813:potassium peroxymonosulfuric acid
keywords: Glycogen synthase kinase 3β; PET; [(11)C]methylsulfide; [(11)C]methylsulfone; [(11)C]methylsulfoxide