title: (17alpha,20E/Z)-iodovinyl- and 16alpha-iodP618-homoestradiol derivatives: synthesis and evaluation for estrogen receptor imaging.
abstract: Three new 125I-radioiodinated estrogens featuring a 13beta-ethyl instead of the natural 13beta-methyl group, i.e. 18-homoestradiols, were synthesized and evaluated as potential estrogen receptor imaging agents. The 16alpha-iodo-18-methylestradiol and the 125I-labeled analog were synthesized from the corresponding 16beta-bromo analog by the halogen-exchange method. The cis-bromohydrin precursor was obtained by bromination of an estrone enolacetate, followed by epimerization and reduction. The isomeric (17alpha,20E/Z)-iodovinyl-18-methylestradiols were prepared via the vinyltin intermediates. Treatment of 18-methyl-17alpha-ethynylestradiol with tri-n-butyltin hydride, in the presence of azobisisobutyronitrile as catalyst and heating at 90-100 degrees C afforded the (17alpha,20E)-tri-n-butylstannyl isomer as the major product. Changing the catalyst for triethyl borane, at room temperature, mainly gave the 20Z-isomer. The nca 125I-labeled analogs were obtained from their corresponding tin intermediates upon treatment with [125I]NaI in the presence of H2O2. The 16alpha-[125I]iodo- and isomeric (17alpha,20E/Z)-[125I]iodovinyl-18-methylestradiols were evaluated for estrogen receptor-mediated uterine uptake in immature female rats. Homologation of the C13-methyl group did improve the uterine uptake of the iodovinyl derivatives, but also increased blood retention, resulting in lower target uptake ratios. In the case of the 16alpha-iodo analog uterine retention decreased upon C13-homologation.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Ali
authors.forename: J
authors.initials: J
authors.lastname: Rousseau
authors.forename: J
authors.initials: J
authors.lastname: Lafrenière
authors.forename: J E
authors.initials: JE
authors.lastname: van Lier
mesh_terms: D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000378:metabolism; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014599:Uterus / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol