ESTROGEN DERIVATIVES FOR EXTERNAL LOCALIZATION OF ESTROGEN-DEPENDENT MALIGNANCY

Abstract

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 sucrose gradient centrifugation indicates that 1 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 h (1.69% dose/g). Iodohexestrol also has a high nonspecific binding in the blood and uterine cytosol. Thyroxine can diminish nonspecific binding in vitro. In vivo, the prior injection of thyroxine increased the 2-h uterus-to-blood ratio from 1.9 to 10.4. The in vitro receptor assay system was helpful in predicting in vivo distribution.