Treatment with rhenium-188-perrhenate and iodine-131 of NIS-expressing mammary cancer in a mouse model remarkably inhibited tumor growth

Introduction: Novel therapeutic modalities are needed for breast cancer patients in whom standard treatments are not effective. Mammary gland sodium/iodide symporter has been identified as a molecular target in breast cancers in humans and in some transgenic mouse models. We report the results of a therapy study with I-131(-) and (ReO4-)-Re-118 of breast cancer in polyoma middle T oncoprotein (PyMT) transgenic mice endogenously expressing the Na+/I- symporter (NIS). Methods: PyMT mice (12-13 weeks old) with one palpable tumor of 0.5-0.8 cm in diameter were used. For the therapy studies, PyMT mice were (1) treated with two intraperitoneal injections of 1.5 mCi of (ReO4-)-Re-188 1 week apart, (2) pretreated for 1 week with 5 mu g of triiodothyronine (T3) followed by two intraperitoneal injections of 1.5 mCi of (131)l- 1 week apart or (3) left untreated. The tumor and normal organ uptakes were assessed by scintigraphic imaging. The thyroid function of treated and control animals was evaluated at the completion of the study by measuring the T3/thyroxine (T4) ratio in their blood. Results: There was significant uptake of I-131(-) and (188)PeO(4)(-) in the primary palpable tumors as well as in nonpalpable tumors, stomachs and thyroids. The tumor uptake after the second injection was 10 times lower in comparison with the first injection. Tumor growth was significantly inhibited in both the I-131(-) and (ReO4-)-Re-188 groups in comparison with the control group, and tumors in the (ReO4-)-Re-188 group increased in size significantly less than in the I-131(-) group. The T3/T4 ratios were calculated to be 27 and 25 for the control group and the (ReO4-)-Re-188 group, respectively; for I-131(-), both the T3 and T4 levels were below detection limit, demonstrating much less effect on the thyroids of treatment with (ReO4-)-Re-188 than with I-131(-). Conclusions: These results prove that NIS expression in breast tumors in animal models allows specific, efficient and safe treatment with a variety of radionuclides transported by NIS. (c) 2005 Elsevier Inc. All rights reserved.