CONVERSION ELECTRON EFFECTED AND ESTROGEN -RECEPTOR MEDIATED CYTOTOXICITY FROM 16ALPHA-RADIOIODO-17BETA-ESTRADIOL IN HUMAN BREAST-CANCER CELLS IN-VITRO

The radiolabeled estrogen, 16alpha-iodo-17beta-estradiol, binds to the estrogen receptor with high affinity and specificity similar to natur al estradiol. Estrogen receptor (ER) complexes accumulate in the nucle us of ER-positive cells. Most carcinomas of the female genitale tract and breast express ER, which have potential to mediate a specific enri chment of radio-estrogens in the nucleus of tumor cells. Receptor imag ing of ER-positive tumors and/or their metastases is possible by using the appropriate radionuclide (i.e. [I-123]). Through their nuclear lo calization radioestrogens tagged with radionuclides emitting very low energy electrons (Auger or conversion electrons) bear potential for th erapy by ER-mediated deposition of lethal doses of ionizing radiation to single cells without affecting neighboring cells. ER-mediated cytot oxicity from the Auger-emitter [I-125]E has already been demonstrated in vitro. In culture of human breast cancer cells, we now demonstrate receptor-mediated cytotoxicity of the clinical used conversion-electro n emitter 16alpha[I-123]iodo-17beta-estradiol ([I-123]E). Non-receptor -mediated cytotoxicity was minimal within dose ranges necessary for re ceptor-mediated cell killing.