Radiotoxicity of auger electron-emitting estrogens in MCF-7 spheroids: A potential treatment for estrogen receptor-positive tumors

To approach treatment of micrometastases of steroid receptor-rich cancers u sing 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 elec tron-emitting estrogen, E-17 alpha-[I-123]-iodovinyl-11 beta-methoxyestradi ol, [I-123]IVhME2, in vitro. After washing, the treated spheroids were diss ociated to single cells and plated for assay of colony survival, whereby we observed a dose-dependent reduction in survival that was inhibited by incl usion of an excess of unlabeled estradiol in the initial incubation with [I -123]IVME2. Spheroids of a range of sizes from 40 to 280 Crm showed similar sensitivity to the Auger electron-emitting estrogen. The mean lethal dose was approximately 700 decays per cell and corresponded to an initial [I-123 ]IVME2 concentration of less than 0.5 nM. If the control and treated sphero ids were not trypsinized but rather were allowed to grow intact, there was not only a significant reduction in the growth of the treated spheroids, bu t in 18 days nearly half became necrotic, while few control spheroids were necrotic, Considering the low concentrations of Auger electron-emitting est rogen required for a significant reduction in survival, we believe this app roach has merit to pursue in vivo, especially in cases where it may be poss ible to target the steroid receptor-rich micrometastases directly, such as ovarian cancer. (C) Radiation Research Society.