Comparison of the distribution of radioiodinated-E-17 alpha-iodovinyl-11 beta-methoxyestradiol and 2-iodo-1,1-bis(4-hydroxyphenyl)-phenylethylene estrogens in the immature female rat.

ABSTRACT

Current therapies for estrogen receptor-positive (ER+) cancers rely heavily on growth prevention by cytostatic agents rather than destruction of the cancer cells. In these studies, we compared the tissue distribution of two radioiodinated estrogens, one a triphenylethylene estrogen, IBHPE, the other steroidal, IVME2. The radioiodoestrogens were prepared using the halodestannylation reaction from the respective tributyltin precursors. The specificity of binding of these radioiodinated estrogens to the estrogen receptor (ER) was established by sucrose-density gradient analyses and their specific activities by comparison with the ER binding of 3H-estradiol of known specific activity. The time-dependent tissue distribution of the two radioiodoestrogens in immature female rats was studied to compare the relative uptake and specific retention of the two estrogens in ER target organs and assess their possible use for imaging ER positive tissues or for Auger electron-mediated ER-directed therapy. While the uterus showed only slightly poorer retention of the nonsteroidal estrogen (IBHPE) than the steroidal estrogen (IVME2), those target tissues that required blood-supplied ligand (e.g., vagina, pituitary) showed substantially higher uptake of the steroidal estrogen. IBHPE showed significantly higher blood levels at all time points. While the tissue-to-muscle ratios for IBHPE in the uterus and ovary were higher initially, the IVME2 showed higher tissue-to-muscle ratios, suggesting that the steroidal estrogen may be the more promising ligand for imaging purposes. However, IBHPE showed excellent uptake by peritoneal target tissues, with much lower concentrations in more distant target tissues (e.g., pituitary) so it might have distinct potential for therapy of intraperitoneal ER-containing cancers.