The Sodium-Iodide Symporter (NIS): NIS-Mediated Radioiodide Therapy

The sodium iodide symporter (NIS) is an intrinsic plasma membrane glycoprotein that mediates the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular the lactating mammary gland. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows diagnostic thyroid scintigraphy, as well as therapeutic radioiodine application in benign and malignant thyroid disease. NIS therefore represents one of the oldest targets for molecular imaging and therapy. Cloning and characterization of the NIS gene has paved the way for the development of a novel cytoreductive gene therapy strategy based on targeted NIS expression in thyroidal and nonthyroidal cancer cells followed by therapeutic application of ¹³¹I or alternative radionuclides, including ¹⁸⁸Re and ²¹¹At. In addition, the possibility of direct and noninvasive imaging of functional NIS expression by ¹²³I and ^99mTc scintigraphy or ¹²⁴I-PET imaging allows the application of NIS as a novel reporter gene. The dual role of NIS as a diagnostic and therapeutic gene and the detection of extrathyroidal endogenous NIS expression in breast cancer open promising perspectives in nuclear medicine and molecular oncology for diagnostic and therapeutic application of NIS outside the thyroid gland.