SPEZIFISCHE BINDUNG VON 16ALPHA-RADIOIOD-OSTRADIOL-17BETA AN OSTROGENREZEPTOREN IN HUMANEN MAMMA-, ENDOMETRIUM- UND OVARIALKARZINOMGEWEBEN IN VITRO

The majority of adenocarcinomas of the female genital organs and breast express steroid hormone receptors. The receptor status is especially important in breast cancer for prognostic and therapeutic considerations. Estrogen receptor (ER) ligands tagged with appropriate radionuclides have potential for (i) assessment of receptor expression in vivo via scintigraphic visualization of ligand receptor binding in primary and metastatic tumors (receptor imaging), and (ii) as carriers for radionuclides for selective radiotherapy of receptor-rich cancer cells (radiohormone therapy) The latter concept is based on the fact that steroid receptors mediate an effective concentration of their ligands in the nucleus of target cells, and that radionuclides with low energy, low range electrons (Auger- or conversion electrons) cause lethal damage of the DNA when located in the cell nucleus. Iodo-16alpha-estradiol-17beta ([I]E) binds to ER with high affinity and specificity. Labelled with the gamma emitter ¹²³I, [¹²³I]E was used for imaging of breast cancer in-vivo. When labelled with the Auger electron emitter ¹²⁵I, [¹²⁵I]E caused selective ER-mediated cytotoxicity for single ER-positive tumor cells. The present paper investigates whether the radioestrogen [¹²⁵I]E in fact binds to ER of clinical human carcinomas. We used cytosols of ER-rich primary and metastatic breast, endometrial, and ovarian carcinomas. Sedimentation velocity analysis in linear sucrose gradients proved estrogen-specific binding of [¹²⁵I]E to a protein fraction which was identified to be ER by monoclonal antibodies (mAk). Specificity of mAk was demonstrated by Western blot analyses. Variations in binding capacity of the mAks, which recognize epitopes in different regions of the receptor protein, indicate heterogeneity of ER-proteins in their DNA binding domain.