title: Amino and iodotamoxifens: synthesis, estrogen receptor affinity and biodistribution.
abstract: Both geometrical isomers (E and Z) of an aminotamoxifen (2) have been prepared as precursors of the corresponding E and Z iodotamoxifens (1). The ability of E and Z-1 and 2 to compete with [3H]estradiol for estrogen receptors in rat uterine cytosol was measured relative to Z-tamoxifen and estradiol. The four tamoxifen derivatives showed affinities ranging from 50% to 1600% of that of tamoxifen. Under the same conditions, tamoxifen's relative binding affinity was 0.2% of that of estradiol. Preparative routes to the radioiodo-tamoxifens, [131I]-E and Z-1, were also developed and provided approximately 100 MBq of 'no carrier added' material in 40-60% radiochemical yield. Study of the biodistribution of these radioligands in tumor-bearing mice demonstrated significant radioactivity in the tumors and in the uterus. For [131I]-E-1, target to background ratios reached 28 for uterus/blood and 10 for tumor/blood; corresponding optimum ratios for [131I]-Z-1 were 10 and 5. A washout study using estradiol indicated selective uptake in the uterus of Swiss white mice. However, tumor uptake and image contrast in humans following intravenous administration of either [131I]-E or Z-1 were insufficient to allow diagnostic use of the radioiodotamoxifens.
authors.affiliation: Department of Chemistry, University of Western Ontario, London, Canada.
authors.forename: L A
authors.initials: LA
authors.lastname: Strickland
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Ponce
authors.forename: D H
authors.initials: DH
authors.lastname: Hunter
authors.forename: P L
authors.initials: PL
authors.lastname: Zabel
authors.forename: J E
authors.initials: JE
authors.lastname: Powe
authors.forename: G
authors.initials: G
authors.lastname: Morrissey
authors.forename: A A
authors.initials: AA
authors.lastname: Driedger
authors.forename: M J
authors.initials: MJ
authors.lastname: Chamberlain
authors.forename: E R
authors.initials: ER
authors.lastname: Tustanoff
mesh_terms: D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007536:Isomerism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D013670:Sodium Pertechnetate Tc 99m; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D013629:Tamoxifen; D013670:Sodium Pertechnetate Tc 99m