The stereoisomers of 17α-[123I]iodovinyloestradiol and its 11β-methoxy derivative evaluated for their oestrogen receptor binding in human MCF-7 cells and rat uterus, and their distribution in immature rats

We studied the potential of both stereoisomers of 17α-[123I]iodovinyloestradiol (E- and Z-[123I]IVE) and of 11β-methoxy-17α-[123I]iodovinyloestradiol (E- and Z-[123I]MIVE) as suitable radioligands for the imaging of oestrogen receptor(ER)-positive human breast tumours. The 17α-[123I]iodovinyloestradiols were prepared stereospecifically by oxidative radio-iododestannylation of the corresponding 17α-tri-n-butylstannylvinyloestradiol precursors. Competitive binding studies were performed in order to determine the relative binding affinity (RBA) of the unlabelled 17α-iodovinyloestradiols for the ER in both human MCF-7 breast tumour cells and rat uterine tissue, compared with that of diethylstilboestrol (DES). Target tissue uptake, retention and uptake selectivity of their 123I-labelled analogues were studied in immature female rats. All four 17α-iodovinyloestradiols showed high affinity for the ER in human MCF-7 cells, as well as rat uterus. Their RBA for the ER showed the following order of decreasing potency: RBA of DES >Z-IVE >Z-MIVE >E-MIVE ≥E-IVE. Neither of these 17α-iodovinyloestradiols showed any significant binding to the sex hormone binding globulin in human plasma. The biodistribution studies showed ER-mediated uptake in the uterus, ovaries and pituitary, that of E- and Z-[123I]MIVE being higher than that of E- and Z-[123I]IVE. High target-to-non-target tissue uptake ratios, especially at longer periods after injection (up to 24 h), were exhibited by both isomers of [123I]MIVE. The uterus-to-blood uptake ratio was higher for E-[123I]MIVE. However, the uterus-to-fat uptake ratio appeared to be higher for the Z-isomer of [123I]MIVE, especially at 24 h after injection. (orig./MG). With 5 figs., 5 tabs