16 Alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol: a radiochemical probe for estrogen-sensitive tissues.

We have synthesized an analog of 16 alpha-iodoestradiol, 11 beta-methoxy-16 alpha-iodo-estra-1,3,5-(10)triene-3,17 beta-diol (16 alpha-iodo-11 beta-methoxyestradiol), as a potential radiopharmaceutical for the in vivo imaging of estrogen-sensitive tissues. This steroid was synthesized labeled with 125I by halogen exchange of the stable intermediate 11 beta-methoxy-16 beta-bromo-17 beta-estradiol with Na125I. The halogen exchange reaction produces the radioiodinated steroid with a 65-80% yield in 3 h. This rapid synthesis and purification of the 125I-labeled estrogen permits a similar synthesis with 123I, a radioisotope with excellent properties for imaging. The 11-methoxy analog is a highly potent estrogen that binds to the estrogen receptor with an affinity equal to that of estradiol. In vivo, 11 beta-methoxy-16 alpha-[125I]iodoestradiol concentrates in an estrogen receptor-dependent manner in the uterus, producing remarkably sustained and much higher uterus to blood ratios than 16 alpha-[125I]iodoestradiol. Thus, this radiosteroid shows great promise, both as a research probe of the estrogen receptor and as a clinical tool for the imaging of estrogen-responsive tumors.