Synthesis and application of 131I-fulvestrant as a targeted radiation drug for endocrine therapy in human breast cancer.

The aim of this study was to label fulvestrant (an endocrine therapy drug for breast cancer) with radioiodine and to evaluate the effect of 131I-fulvestrant on inhibiting the growth of human breast cancer and its influence on major organs in nude mice. Fulvestrant was labeled with radioiodine using a modified chloramine T method, and its chemical properties were assessed using traditional methods. The binding affinity of 131I-fulvestrant was measured by radioligand binding assays, and its antiproliferative activity was determined by MTT assays. The ability of 131I-fulvestrant to kill MCF-7 and MDA-MB-231 cells was also detected by MTT assays. We established MCF-7 cell xenografts in nude mice and monitored tumor growth and critical organ function. When the labeling reactions were conducted for 5 min at room temperature at pH 7.5, the radiochemical yield of the 131I labeling to fulvestrant was 62.34±1.8%, the radiochemical purity was 98.6±3.4%, and the half maximal inhibitory concentration (IC50) at 48 h was 35 µCi. 131I-fulvestrant was stable, and its binding affinity to estrogen receptor-positive (ER+) MCF-7 cells was also retained. In addition, 131I-fulvestrant exhibited similar cytotoxicity in MCF-7 and MDA-MB-231 cells, although MCF-7 cells showed a slightly more pronounced response. 131I-fulvestrant continuously exerted a tumor suppressive effect on MCF-7 cells but not on MDA-MB-231 cells (P<0.05). Upon intravenous injection of 131I-fulvestrant into nude mice, the radioactivity distribution corresponded to ER expression patterns and was primarily confined to the tumor. 131I-fulvestrant exhibited a precise growth inhibition effect on MCF-7 breast cancer cells, and its effects on general conditions of nude mice and their major organs were manageable. Therefore, radioiodine labeling of fulvestrant was successful and could be used to develop novel drugs for breast cancer by superimposing the benefits of radiotherapy and endocrine therapy.