title: 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone: synthesis and target tissue selective uptake of a progestin receptor based radiotracer for positron emission tomography.
abstract: We have synthesized 21-[18F]fluoro-16 alpha-ethyl-19-norprogesterone (FENP), a high affinity ligand for the progesterone receptor, labeled with the positron-emitting radionuclide fluorine-18 (t1/2 = 110 min). The synthesis proceeds in two steps from 21-hydroxy-16 alpha-ethyl-19-norprogesterone and involves [18F]fluoride ion displacement of the 21-trifluoromethanesulfonate (21-triflate). This material is purified by HPLC and is obtained in 4-30% overall yield (decay corrected) within 40 min after the end of bombardment to produce [18F]fluoride ion. The effective specific activity, determined by competitive radioreceptor binding assays, is 700-1400 Ci/mmol. In vivo, [18F]FENP demonstrates highly selective, receptor-mediated uptake by the uterus of estrogen-primed rats; the uterus to blood and uterus to muscle ratios were respectively 26 and 16 at 1 h and 71 and 41 at 3 h after injection. The high target tissue selectivity of this uptake suggests that this compound may be useful for the in vivo imaging of progestin target tissues and receptor-rich tumors (such as human breast tumors) by positron emission tomography.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana 61801.
authors.forename: M G
authors.initials: MG
authors.lastname: Pomper
authors.forename: J A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: M J
authors.initials: MJ
authors.lastname: Welch
authors.forename: J W
authors.initials: JW
authors.lastname: Brodack
authors.forename: C J
authors.initials: CJ
authors.lastname: Mathias
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes; D009652:Norpregnenes / Q000138:chemical synthesis*; D009653:Norprogesterones / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D011282:Pregnenediones / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D045167:Progesterone Congeners; D011397:Promegestone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011980:Receptors, Progesterone / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D004967:Estrogens; D005462:Fluorine Radioisotopes; D009652:Norpregnenes; D009653:Norprogesterones; D011282:Pregnenediones; D045167:Progesterone Congeners; D011980:Receptors, Progesterone; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; C056437:21-fluoro-16-ethyl-19-norprogesterone; D011374:Progesterone; D011397:Promegestone