SPECIFIC BINDING OF IODO-16ALPHA-ESTRADIO L-17BETA TO ESTROGEN-RECEPTORS IN HUMAN BREAST, ENDOMETRIAL, AND OVARIAN-CARCINOMA TISSUE IN-VITRO

The majority of adenocarcinomas of the female genital organs and breas t express steroid hormone receptors. The receptor status is especially important in breast cancer for prognostic and therapeutic considerati ons. Estrogen receptor (ER) ligands tagged with appropriate radionucli des have potential for (i) assessment of receptor expression in vivo v ia scintigraphic visualization of ligand receptor binding in primary a nd metastatic tumors (receptor imaging), and (ii) as carriers for radi onuclides for selective radiotherapy of receptor-rich cancer cells (ra diohormone therapy). The latter concept is based on the fact that ster oid receptors mediate an effective concentration of their ligands in t he nucleus of target cells, and that radionuclides with low energy, lo w range electrons (Auger- or conversion electrons) cause lethal damage of the DNA when located in the cell nucleus. Iodo-16-alpha-estradiol- 17beta ([I]E) binds to ER with high affinity and specificity. Labelled with the gamma emitter I-123, [I-123]E was used for imaging of breast cancer in-vivo. When labelled with the Auger electron emitter I-125, [I-125]E caused selective ER-mediated cytotoxicity for single ER-posit ive tumor cells. The present paper investigates whether the radioestro gen [I-125]E in fact binds to ER of clinical human carcinomas. We used cytosols of ER-rich primary and metastatic breast, endometrial, and o varian carcinomas. Sedimentation velocity analysis in linear sucrose g radients proved estrogen-specific binding of [I-125]E to a protein fra ction which was identified to be ER by monoclonal antibodies (mAk). Sp ecificity of mAk was demonstrated by Western blot analyses. Variations in binding capacity of the mAks, which recognize epitopes in differen t regions of the receptor protein, indicate heterogeneity of ER-protei ns in their DNA binding domain.