Concentration of [16 alpha-125I]iodoestradiol in human ovarian tumors in vivo and correlation with estrogen receptor content.
The gamma emitting estrogen [16 alpha-125I]iodoestradiol was administered to 11 patients with ovarian cancer and 1 patient with endometrial cancer. At specific times after the administration of the tracer, portions of the tumor and of control tissues, fat and muscle, were removed and counted. The amount of radioactivity in these tissues was compared to the cytosolic estrogen receptor content of the tumor, measured by Sephadex LH-20 gel filtration, in biopsy specimens taken before the injection of the tracer. There was a strong correlation (p less than 0.005) between the estrogen receptor concentration in the biopsied tumor and the amount of radioactivity in the tumor. There was no correlation between the isotope in the muscle and the tumor receptor, nor between the radioactivity in the tumor and that in fat or muscle. As would be expected for a steroid receptor mediated process, the bulk of the total tissue radioactivity was present in the nuclear compartment of the tumors. This pattern was not observed in the muscle. Furthermore, the nuclear radioactivity in the tumors was positively correlated with the cytosolic estrogen receptor content. These experiments demonstrate that under in vivo conditions this gamma emitting estrogen is concentrated in tumors in a manner that is dependent upon the estrogen receptor. It was also found that the concentrations of radioactivity in the blood were high, producing low tumor to blood ratios. The blood level of isotope was not due to the presence of the unmetabolized steroid, which disappeared from blood rapidly, but was caused by circulating metabolites of the injected steroid. Since the concentration of the isotope in the tumor was dependent upon the estrogen receptor level, it would appear from these experiments that it is theoretically possible to use such compounds to image and monitor tumors that contain estrogen receptors. However, rapid metabolism would seem to preclude the use of 16 alpha-iodoestradiol itself for this purpose. These studies point to the possibility that the synthesis of analogs of 16 alpha-iodoestradiol, sterically protected against inactivation by rapid metabolism, may lead to a radiopharmaceutical agent that would be useful for imaging and monitoring estrogen receptor containing tumors.
D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000032:analysis / Q000648:ultrastructure; D004958:Estradiol / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000032:analysis* / Q000473:pathology; D011960:Receptors, Estrogen / Q000032:analysis*; D014594:Uterine Neoplasms / Q000032:analysis
D007457:Iodine Radioisotopes; D011960:Receptors, Estrogen; D004958:Estradiol; C024871:16 alpha-iodoestradiol