title: 20-[18F]fluoromibolerone, a positron-emitting radiotracer for androgen receptors: synthesis and tissue distribution studies.
abstract: To develop an androgen receptor-based, positron-emitting imaging agent for prostate tumors, we have prepared 20-fluoromibolerone (F-Mib) and evaluated its tissue distribution. This compound was synthesized in eight steps from 7 alpha-methyl-19-nortestosterone, with fluorine introduced in the penultimate step by fluoride ion displacement on a spirocyclic sulfate. Fluoromibolerone was obtained in 9%-19% radiochemical yield (decay corrected), at 1.5 hr after bombardment, with an effective specific activity of 217-283 Ci/mmol. The relative binding affinity of F-Mib is 53 (versus R1881 = 100 or mibolerone = 118). In tissue distribution studies in diethylstilbestrol-treated male rats, 18F-Mib demonstrates high target/tissue uptake efficiency and selectivity: the prostate uptake at 0.5 hr and 4 hr is 1.0%-1.3% injected dose/gram tissue (ID/g) and 0.5%-0.6% ID/g, respectively; the prostate-to-blood and the prostate-to-muscle (non-target) ratios are both ca. 4 at 0.5 hr, and increase to ca. 12 by 4 hr after injection. The observed distribution of 18F-Mib suggests that it may be useful for in vivo imaging of prostatic tumors in man by positron emission tomography.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana 61801.
authors.forename: A J
authors.initials: AJ
authors.lastname: Liu
authors.forename: J A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: H F
authors.initials: HF
authors.lastname: VanBrocklin
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes; D008297:Male; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011467:Prostate / Q000000981:diagnostic imaging*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000032:analysis*; D045165:Testosterone Congeners / Q000138:chemical synthesis; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005462:Fluorine Radioisotopes; D011944:Receptors, Androgen; D045165:Testosterone Congeners; C066844:20-fluoromibolerone; D009277:Nandrolone