title: 17 alpha-Z-[125I]iodovinyloestradiol and its 3-acetate: chemical synthesis in vivo distribution studies in the rat. Comparison of tissue accumulation and metabolic stability with 17 alpha-E-[125I]iodovinyl and 16 alpha-[125I]iodo oestradiols.
abstract: Certain oestrogens on substitution with halogens, have been shown to retain receptor binding affinity and accumulate in target tissues and therefore could, when labelled with gamma-emitting halogen isotope, act as radiopharmaceuticals for the imaging of receptor positive breast tumours. In order to evaluate putative radiopharmaceuticals, 17 alpha-Z-iodovinyloestradiol ((17 alpha,20Z)-21-iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate have been chemically synthesized and labelled with 125I. Tissue distribution studies in female rats have been compared to those obtained using 17 alpha-E-[125I]iodovinyloestradiol ((17 alpha,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol) and its 3-acetate and to 16 alpha-[125I]iodo oestradiol (1,3,5(10)-estratien-16 alpha-[125I]iodo-3,17 beta-diol). All compounds showed a similar tissue distribution with the highest concentrations (cpm/g tissue) in the thyroid greater than liver greater than uterus greater than kidney greater than lung greater than blood greater than heart, spleen. The concentration in the uterus was highest after injection of 17 alpha-Z-iodovinyloestradiols or 16 alpha-iodo oestradiol. Target (uterus) to background (blood) tissue ratios were highest after injection of 17 alpha-Z-iodovinyloestradiol-3-acetate and 16 alpha-iodo oestradiol (6:1). Deiodination in vivo took place to a small degree, amounting to 1.6%, 0.9% and 0.35% of the injected dose after 4 hr with the 17 alpha-Z, 17 alpha-E and 16 alpha compounds, respectively. For reasons of chemical expediency and consideration of the biological results 17 alpha-Z-iodovinyloestradiol-3-acetate is the compound of choice for the detection of oestrogen receptor positive tissues.
authors.affiliation: Department of Chemical Pathology, Hammersmith Hospital, London, U.K.
authors.forename: E K
authors.initials: EK
authors.lastname: Symes
authors.forename: P B
authors.initials: PB
authors.lastname: Bishop
authors.forename: W F
authors.initials: WF
authors.lastname: Coulson
authors.forename: A G
authors.initials: AG
authors.lastname: Davies
mesh_terms: D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D007457:Iodine Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis*; D013237:Stereoisomerism; D013961:Thyroid Gland / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D014599:Uterus / Q000737:chemistry / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol; C024871:16 alpha-iodoestradiol; C034555:17 alpha-iodovinylestradiol