title: Receptor binding and biological effects of three 125I-iodinated estrogen derivatives in human breast cancer cells (MCF-7).
abstract: Three 125I-iodinated estrogen derivatives; 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]IME2), E-17 alpha-[125I]iodovinylestradiol ([125I]IVE2) and E-17 alpha-[125I]iodovinyl-11 beta-methoxyestradiol ([125I]MIVE2) were synthesized with high specific activities and their binding characteristics and biological effects were analyzed in vitro using the estrogen-receptor-positive human breast cancer cell line MCF-7. Direct and competitive bindings in a whole cell assay indicated that the three derivatives bound to the estrogen receptor (ER) with high affinity. The dissociation constants of the three compounds were higher than the one found for tritiated E2 suggesting that the presence of the methoxy and the vinyl groups decreased the binding affinity. The decreasing affinity order is: [3H]E2 > or = [125I]IME2 > [125I]IVE2 > [125I]MIVE2. The three unlabeled derivatives as well as E2 have been found to activate the vitellogenin promoter fused to the chloramphenicol acetyl transferase reporter gene transfected into MCF-7 cells. This assay showed that the ER is activated in the presence of the three compounds. Unlabeled IME2 produced stimulatory effects similar to those of E2 on MCF-7 growth in vitro. Unlabeled IVE2 and MIVE2 at concentrations lower than 10(-8) M enhanced MCF-7 growth but at a lower level than E2 and IME2 did. Our results clearly indicate that the three derivatives behave like estrogens and that they would be excellent candidates for imaging or monitoring ER-containing breast tumors. Because its affinity for the ER is greatest, IME2 would be the best-suited of the three as a radiotracer.
authors.affiliation: Institut d'Oncologie Cellulaire et Moleculaire Humaine, Bobigny, France.
authors.forename: B
authors.initials: B
authors.lastname: Souttou
authors.forename: J L
authors.initials: JL
authors.lastname: Moretti
authors.forename: J
authors.initials: J
authors.lastname: Gros
authors.forename: D
authors.initials: D
authors.lastname: Guilloteau
authors.forename: M
authors.initials: M
authors.lastname: Crepin
mesh_terms: D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045166:Estradiol Congeners / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D015394:Molecular Structure; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014819:Vitellogenins / Q000235:genetics
chemical_list: D045166:Estradiol Congeners; D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D014819:Vitellogenins