title: Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits.
abstract: [4-18F] 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol [( 4-18F] fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4'-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propan ol in 19% yield. A modified Schiemann reaction on this product resulted in [4-18F]fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2 h. [4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4-18F]fluconazole to a relatively uniform distribution of radioactivity in most organs.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston 02114.
authors.forename: E
authors.initials: E
authors.lastname: Livni
authors.forename: A J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: I
authors.initials: I
authors.lastname: Sinclair
authors.forename: D R
authors.initials: DR
authors.lastname: Elmaleh
authors.forename: N M
authors.initials: NM
authors.lastname: Alpert
authors.forename: S
authors.initials: S
authors.lastname: Weiss
authors.forename: J A
authors.initials: JA
authors.lastname: Correia
authors.forename: D
authors.initials: D
authors.lastname: Webb
authors.forename: R
authors.initials: R
authors.lastname: Dahl
mesh_terms: D000818:Animals; D015725:Fluconazole / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D015725:Fluconazole