RADIOIODINATED LIGANDS FOR THE ESTROGEN-RECEPTOR - EFFECT OF 3-ORTHO-METHYLATION ON TISSUE DISTRIBUTION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (10) , 1116-1121
Abstract
The 3-o-methyl ethers of 17.alpha.-[125I]iodovinylestradiol and 17.alpha.-[125I]iodovinyl-11.beta.-methoxyestradiol were prepared in 95 and 89% isolated yields, respectively, at the no-carrier-added level from the corresponding (tri-n-butystannyl)-vinyl intermediates. The new radioligands were evaluated in immature female rats to determine their uptake in, and selectivity for, estrogen-receptor-containing tissues. At 0.5-6 h after administration, both agents showed preferential uptake and retention by the target tissue. The values for the 11.beta.-methoxy derivative, however, were significantly better than those of the 11-unsubstituted compound. Compared with the parent 3-hydroxy radioligands, the [125I]VE2-3-o-Me had lower uptake and target-to-blood ratios at all time periods, but by 6 h the [125I]VME2-3-o-Me compound showed as high an uptake in the uterus and higher uterus-to-blood ratios. This may be related to metabolic cleavage of the 3-o-methyl group generating the parent compound, which is then sequestered by the target tissue. Apparently, 123I-labeled VME2-3-o-Me would be a good candidate for the in vivo gamma imaging of estrogen-containing tissues. [The presence of specific hormone receptors in human breast cancer in regard to therapy and prognosis is discussed.].