Biologic activity of the iodoestrogens and their use in breast cancer

Several iodinated estrogens, 6-iodoestra-1,3,5(10), 6-tetraene-3, 17 beta-diol (4) 16 beta-iodo-estradiol (3) were shown to displace 3H-estradiol (1b) from the uterine cytosol receptor by a competitive type of inhibition. The three compounds translocated the cytosol receptor to the nucleus in vitro and increased mouse uterine weight in vivo. In all tests the relative activities were 16 alpha-(2a) greater than 16 beta-(3a) greater than 6-(4a). When the compounds were made with [125I] the 16 alpha-[125I]-iodoestradiol (2b) bound with high affinity, Kd = 0.4 x 10(-10), to the 8S cytosol receptor. No high affinity binding could be demonstrated for the 6-[125I]-iodoestratetraene (4b). In in vivo experiments following the administration of 16 alpha-[125]-iodoestradiol (2b) to rats, high levels of radioactivity were found in the uterus, liver and thyroid but only in the liver and thyroid following administration of 6-[125I]-iodoestratetraene (4b). After administration of (2b) to rats with DMBA-induced mammary tumors, no tumor concentration of radioactivity could be detected by imaging. When (4b) was administered similarly, radioactivity could be detected in some of the tumors by imaging. The radioactivity was associated with non-specific 4S proteins.