Radiotoxicity of Auger electron-emitting estrogens in MCF-7 spheroids: a potential treatment for estrogen receptor-positive tumors.

Abstract

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, E-17alpha-[123I]-iodovinyl-11beta-methoxyestradiol, [123I]IVME2, 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 [123I]IVME2. Spheroids of a range of sizes from 40 to 280 microm showed similar sensitivity to the Auger electron-emitting estrogen. The mean lethal dose was approximately 700 decays per cell and corresponded to an initial [123I]IVME2 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.

• Authors: T Kearney, A Hughes, R N Hanson, E R DeSombre
• Journal: Radiation research (Radiat Res) Vol. 151 Issue 5 Pg. 570-9 (May 1999) ISSN: 0033-7587 [Print] United States
• PMID: 10319730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Iodine Radioisotopes
• Receptors, Estrogen
• Estradiol
• 17 alpha-iodovinyl-11 beta-methoxyestradiol

Topics

• Animals
• Breast Neoplasms (chemistry, pathology, radiotherapy)
• Cell Survival (radiation effects)
• Estradiol (analogs & derivatives, therapeutic use)
• Female
• Humans
• Iodine Radioisotopes (therapeutic use)
• Mice
• Mice, Nude
• Receptors, Estrogen (analysis)
• Spheroids, Cellular
• Tumor Cells, Cultured