Estrogen derivatives for the external localization of estrogen-dependent malignancy

Four radioiodinated estrogen derivatives were studied to determine their affinity for the estrogen-binding protein found in the cytosol of rabbit and rat uteri. In vitro determination of the binding properties by competitive-binding experiments and by sucrose-gradient centrifugation indicates that one of the derivatives, iodohexestrol, binds to the cytosol estrogen-binding protein. This in vitro behavior was related to in vivo distribution. Studies in immature female rats showed high uterine uptake of iodohexestrol at 2 hr (1.69% dose/gm). Iodohexestrol also has a high nonspecific binding in both the blood and the uterine cytosol. Thyroxine can diminish the nonspecific binding in vitro; in vivo the prior injection of thyroxine increased the 2-hr uterus-to-blood ratio from 1.9 to 10.4 The in vitro receptor-assay system was helpful in predicting in vivo distribution.