Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Ovarian cancer represents the fifth leading cause of cancer death among women in the United States, with 416 000 deaths expected this year. This study was carried out to investigate the potential of sodium iodide symporter (NIS)-mediated radioiodide therapy as a novel approach for ovarian cancer treatment. Radioiodide is routinely and effectively used for the treatment of benign and malignant thyroid disease as a result of native thyroidal expression of NIS, which mediates iodide uptake. In vitro gene transfer studies in ovarian cancer cells revealed a 12- and five-fold increase in iodide uptake when transduced with Ad/CMV/NIS or Ad/MUC1/NIS, respectively. Western blot/immunohistochemistry confirmed NIS protein expression. In vivo ovarian tumor xenografts were infected with the adenoviral constructs. I-123 imaging revealed a clear image of the CMV/NIS-transduced tumor, with a less intense image apparent following infection with MUC1/NIS. Therapeutic doses of I-131 following CMV/NIS infection caused a mean 53% reduction in tumor volume (P<0.0001). MUC1/NIS-transduced tumors did not regress, although at 8 weeks following therapy, tumor volume was significantly less that of control animals (166 versus 332%, respectively, P<0.05). This study represents a promising first step investigating the potential for NIS-mediated radioiodide imaging and therapy of ovarian tumors.