Studies with I-125-MIVE/sub 2/ in human breast cancer cells (MCF-7)

I-125-17 alpha-iodovinyl 11-beta methoxyestradiol, I-125-MIVE/sub 2/, a gamma-emitting analog of estradiol which binds to the estradiol receptor was studied to determine the specificity and affinity of this compound. Although I-125-MIVE/sub 2/ has shown promising results using immature rat cytosol, the human breast cancer cell line, MCF-7, is a more relevant model for clinical studies. In vitro determination of receptor binding by DCC assay indicates that I-125-MIVE/sub 2/ binds specifically and with a high affinity to cytosolic estrogen receptor prepared from MCF-7 cells. H-3 estradiol binds to the receptor with approximately twice the affinity of I-125-MIVE/sub 2/ (Kd=1.33 X 10/sup -9/M, I-125 MIVE/sub 2/; Kd = 5.1 X 10/sup -10/M, H-3 estradiol). Stimulation of thymidine incorporation (approximately 300% above control levels) is also observed after exposure to 1 x 10/sup -9/M MIVE/sub 2/. Preliminary data show receptor-mediated uptake by the uterus and by MCF-7 tumors in biodistribution studies in athymic nude mice injected with I-125-MIVE/sub 2/. At 4 h, uterus to blood ratios are 20.5 and uterus to non-target tissue ratios are 12.9. In light of the fact that this compound can be prepared with a high specific activity, I-125-MIVE/sub 2/ may have potential as a radiotracer for imaging estrogen receptor positive breast tumors