Abstract
Previous studies have demonstrated that Auger electron-emitting estrogens, when associated with the estrogen receptor (ER), can effect breaks in DNA and ER-dependent radiotoxicity. To evaluate the potential of [123I]-iodoestrogens, ([123I]-IE) to treat ER-positive human cancer cells, we have studied the effect of incubation of [123I]-IE with ER-positive MCF-7 breast cancer cells on cell survival in vitro and found that subnanomolar concentrations of [123I]-IE effectively reduce survival, with a mean lethal dose of about 800 decays per cell. MCF-7 cells incubated 30 min with 2 nM [123I]-IE (13 MBq/ml) showed a 2 log reduction in the ability to form tumors in immunodeficient mice. Evaluation of a mathematical model for [123I]-IE therapy for intraperitoneal micrometases in vivo in the mouse, based on variables related to the (a) specific activity of [123I]-IE; (b) its affinity for ER; (c) the characteristics of the uptake and retention of [123I]-IE by the target cells; (d) the concentration of ER in the tumor cells and (e) the tumor weight suggest that such therapy may be feasible.
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