title: Synthesis, receptor binding, and tissue distribution of (17 alpha,20E)- and (17 alpha,20Z)-21-[125I]iodo-19-norpregna-1,3,5(10), 20-tetraene-3,17-diol .
abstract: The isomeric (17 alpha,20E)- and (17 alpha,20Z)-(iodovinyl)estradiol derivatives 3 and 6, and their no-carrier-added (nca) [125I]iodovinyl analogues, were tested for their relative target tissue retention and binding affinity for the estrogen receptor. The (iodovinyl)estradiols 3 and 6 were prepared via destannylation of the (17 alpha,20E)- and (17 alpha,20Z)-tributylstannyl precursors 2 and 4 with retention of configuration. Selective formation of the E or Z isomers 2 and 4 during the reaction of 17 alpha-ethynylestradiol 1a with tri-n-butyltin hydride was controlled by the presence or absence of the catalyst, the polarity of the solvent, and the reaction temperature. The nca [125I]iodovinyl analogues [125I]-3a and [125I]-6a were obtained in good radiochemical yield and high purity by treatment of 2a and 4a with [125I]NaI in the presence of H2O2 and chloroamine-T, respectively. Of the two isomeric iodovinyl derivatives 3 and 6, the 20Z isomer 6a exhibited the highest receptor binding affinity and the [125I]-6a gave the highest in vivo receptor-mediated target tissue uptake.
authors.affiliation: MRC Group in the Radiation Sciences, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Ali
authors.forename: J
authors.initials: J
authors.lastname: Rousseau
authors.forename: M A
authors.initials: MA
authors.lastname: Ghaffari
authors.forename: J E
authors.initials: JE
authors.lastname: van Lier
mesh_terms: D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D007536:Isomerism; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D011960:Receptors, Estrogen; D004958:Estradiol; C034555:17 alpha-iodovinylestradiol