-Z-[125I]iodovinyloestradiol and its 3-acetate: Chemical synthesis and in vivo distribution studies in the rat

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 γ-emitting halogen isotope, act as radiopharmaceuticals for the imaging of receptor positive breast tumours. In order to evaluate putative radiopharmaceuticals, 7α-Z-iodovinyloestradiol (17α,20Z)-21-iodo-19-norpregna-1,3,5(10),20-tetraene-3,17β-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 17α-E-[125I]iodovinyloestradiol((17α,20E)-21-[125I]iodo-19-norpregna-1,3,5(10),20-tetraene-3,17β-diol)and its 3-acetate and to 16α-[su125I]iodo estradiol (1,3,5(10)-estratrien-16α-[125I]iodo-3,17β-diol). All compounds showed a similar tissue distribution with the highest concentrations (cpm/g tissue) in the thyroid > liver > uterus > kidney > lung > blood > heart, spleen. The concentration in the uterus was highest after injection of 17α-Z-iodovinyloestradiols or 16α-iodo oestradiol. Target (uterus) to background (blood) tissue ratios were highest after injection of 17α-Z-iodovinyloestradiol-3-acetate and 16α-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 4hr with the 17α-Z, 17α-E and 16α compounds, respectively. For reasons of chemical expediency and consideration of the biological results 17α-Z-iodovinyloestradiol-3-acetate is the compound of choice for the detection of oestrogen receptor positive tissues.