title: Practical synthesis of precursor of [N-methyl-11C]vorozole, an efficient PET tracer targeting aromatase in the brain.
abstract: A practical method to prepare precursor of [N-methyl-(11)C]vorozole ([(11)C]vorozole), an efficient positron emission tomography (PET) tracer for imaging aromatase in the living body, was established. Sufficient amount of the racemate including norvorozole, a demethylated vorozole derivative used as a precursor of [(11)C]vorozole, became available by means of high-yield eight-step synthesis. The enantiomers were separated by preparative HPLC using a chiral stationary phase column to give optically pure norvorozole and its enantiomer. From the latter, ent-[(11)C]vorozole, an enantiomer of [(11)C]vorozole, was prepared and used in the PET study for the first time, which was shown to bind very weakly to aromatase in rhesus monkey brain supporting the previous pharmacological results. The stable supply of norvorozole will facilitate further researches on aromatase in the living body including brain by the PET technique.
authors.affiliation: RIKEN Center for Molecular Imaging Science, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Gen
authors.initials: G
authors.lastname: Yamagishi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Ayako
authors.initials: A
authors.lastname: Hosoya
authors.forename: Kayo
authors.initials: K
authors.lastname: Onoe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagata
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hosoya
mesh_terms: D000818:Animals; D001141:Aromatase / Q000032:analysis*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D008253:Macaca mulatta; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D014230:Triazoles; C060523:vorozole; D001141:Aromatase