Cytotoxicity of Receptor-Mediated 16 [125I]Iodo-estradiol in Cultured MCF-7 Human Breast Cancer Cells

Abstract

Therapeutic strategies using 125I-labeled steroid hormones are attractive in light of the estrogen dependence of many human breast cancers and the favorable microdosimetry resulting from 125I decay. We determined the uptake, specific estrogen receptor (ER) binding, and cytotoxicity of 16 alpha-[125I]iodoestradiol in cultured MCF-7 human breast cancer cells. The cytotoxicity of receptor-mediated 125I appears to be sufficient in MCF-7 cells to warrant in vivo experimentation. Furthermore, cytotoxicity not specific to ERs is minimal within the dose range necessary for ER saturation and specific cell killing. Competitive toxicity studies using nonradioactive 17 beta-estradiol demonstrate an unequivocal relationship between ER binding and clonogenic viability.

Therapy of Estrogen Receptor-Positive Micrometastases in the Peritoneal Cavity with Auger Electron-Emitting Estrogens - Theoretical and Practical Considerations

“…Clearly, there is now substantial evidence that an Auger electron± emitting nuclide, covalently attached to an estrogen in a manner in which it retains its high af® nity and speci® city for the estrogen receptor, can effect radiotoxicity in estrogen receptor-containing cells. While early investigations used [ 125 I]-IE and required freezing cells in vitro to accumulate suf® cient decays for measurable cytotoxicity (11), more recent reports have been able to observe such effects without freezing, but using conditions which could not be replicated in vivo (12). Recognizing that for in vivo work it would be necessary to use a nuclide with a shorter half-life than 60 days, we turned initially to studies with bromine-80m (13,14).…”

Dna Damage Induction by125I-Estrogen

“…ER-dependent radiotoxicity has been reported previously using 16a- [ '251]iodoestradiol in cultured MCF-7 breast cancer both when cells were frozen to accumulate decays ( 5 ) and when in vitro conditions were controlled to maximize retention of ligand in cells (6,7). In the present study we investigated DNA ssb and dsb induction to provide a basis for understanding the cytotoxic effects of '251 decay.…”

Evaluation of a bromine-76-labeled progestin 16α,17α-dioxolane for breast tumor imaging and radiotherapy: in vivo biodistribution and metabolic stability studies

“…Although a number of steroids labeled with bromine and iodine radioisotopes have been prepared [7][8][9][10][11][12] and studied, especially in terms of their potential for selective radiotherapy, their use in imaging studies, particularly in humans, has been more limited [12]. Nevertheless, previous studies have established the feasibility of using various Auger electron-emitting isotopes for selective cellular therapy [13][14][15][16][17][18][19][20][21][22][23].…”