Radiotoxicity of Auger Electron-Emitting Estrogens in MCF-7 Spheroids: A Potential Treatment for Estrogen Receptor-Positive Tumors

• Published in: Radiation research 1999-05, Vol.151 (5), p.570-579
• Main Authors: Kearney, Thomas, Hughes, Alun, Hanson, Robert N., DeSombre, Eugene R.
• Format: Article
• Language: English
• Subjects: Animals; Augers; Biological and medical sciences; Breast Neoplasms - chemistry; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Cancer; Cell growth; Cell Survival - radiation effects; Cells; Cellular spheroids; Estradiol - analogs & derivatives; Estradiol - therapeutic use; Estrogens; Female; Genital system. Mammary gland; Half lives; Humans; Iodine Radioisotopes - therapeutic use; Medical sciences; Mice; Mice, Nude; Radiation therapy and radiosensitizing agent; Radioactive decay; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Receptors, Estrogen - analysis; Space life sciences; Spheroids; Spheroids, Cellular; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3580033

To approach treatment of micrometastases of steroid receptor-rich cancers using estrogen receptor-directed therapy with Auger electrons, multicellular spheroids of the estrogen receptor-rich human breast cancer cell line, MCF-7, were prepared and exposed to a range of concentrations of an Auger electron-emitting estrogen, ${\rm E}\text{-}17\alpha \text{-}[^{123}{\rm I}]\text{-iodovinyl-}11\beta \text{-methoxyestradiol}$, $[^{123}{\rm I}]{\rm IVME}2$, in vitro. After washing, the treated spheroids were dissociated to single cells and plated for assay of colony survival, whereby we observed a dose-dependent reduction in survival that was inhibited by inclusion of an excess of unlabeled estradiol in the initial incubation with $[^{123}{\rm I}]{\rm IVME}2$. Spheroids of a range of sizes from 40 to 280 μm showed similar sensitivity to the Auger electron-emitting estrogen. The mean lethal dose was approximately 700 decays per cell and corresponded to an initial $[^{123}{\rm I}]{\rm IVME}2$ concentration of less than 0.5 nM. If the control and treated spheroids were not trypsinized but rather were allowed to grow intact, there was not only a significant reduction in the growth of the treated spheroids, but in 18 days nearly half became necrotic, while few control spheroids were necrotic. Considering the low concentrations of Auger electron-emitting estrogen required for a significant reduction in survival, we believe this approach has merit to pursue in vivo, especially in cases where it may be possible to target the steroid receptor-rich micrometastases directly, such as ovarian cancer.