Sodium Iodide Symporter and the Radioiodine Treatment of Thyroid Carcinoma
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REVIEW ARTICLE
Sodium Iodide Symporter and the Radioiodine Treatment of Thyroid Carcinoma June-Key Chung & Hye Won Youn & Joo Hyun Kang & Ho Young Lee & Keon Wook Kang
Received: 1 December 2009 / Accepted: 9 December 2009 / Published online: 26 February 2010 # Korean Society of Nuclear Medicine 2010
Abstract Since the specific accumulation of iodide in thyroid was found in 1915, radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide uptake occurs across the membrane of the thyroid follicular cells and cancer cells through an active transporter process mediated by the sodium iodide symporter (NIS). The NIS coding genes were cloned and identified from rat and human in 1996. Evaluation of the NIS gene and protein expression is critical in the management of thyroid cancer, and several approaches have been tried to increase NIS levels. Identification of the NIS gene has provided a means
of expanding its role in the radionuclide gene therapy of nonthyroidal cancers as well as thyroid cancer. In this article, we explain the relationship between NIS expression and the treatment of thyroid carcinoma with I-131, and we include a review of the results of our experimental and clinical trials. Keywords Sodium iodide symporter (NIS) . Thyroid cancer . I-131 . Gene therapy
Sodium/Iodide Symporter in Thyroid Cancer J.-K. Chung (*) : H. W. Youn : H. Y. Lee : K. W. Kang Department of Nuclear Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Jongro-gu, Seoul 110-744, Korea e-mail: [email protected] J.-K. Chung : H. W. Youn : K. W. Kang Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea J.-K. Chung : H. W. Youn : K. W. Kang Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Korea J.-K. Chung : H. W. Youn : H. Y. Lee : K. W. Kang Research Center of Radiation Medicine, Seoul National University College of Medicine, Seoul, Korea J. H. Kang Molecular Imaging Research Center, KIRAMS, Seoul, Korea
The specific accumulation of iodide in the thyroid gland was discovered in 1915, and its clinical implications were quickly realized. Today, radioiodine is widely used to diagnose and treat thyroid disorders, such as thyroid cancer, and I-131 has been used as the treatment of choice for metastatic thyroid cancer for more than 60 years [1]. However, the mechanism responsible for this iodine specificity was determined only recently. It is now known that the iodide ion is transported into thyroid cells with a sodium ion by sodium/iodide symporter (NIS). Actually, the force driving iodide uptake is generated by the sodium ion transmembrane concentration gradient, which is produced and maintained by the sodium-potassium pump, ATPase (Fig. 1). The NIS gene was identified in 1996 [2], and its product, hNIS protein, is now known to be an intrinsic membrane protein with 13 transmembrane domains that is composed of 643 amino acids. Furthermore, the recent cloning of the NIS gene enabled the molecular mechanisms underlying
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