Sodium Iodide Symporter in Health and Disease

Abstract

Radioiodine-concentrating activity in thyroid tissues has allowed the use of radioiodine as a diagnostic and therapeutic agent for patients with thyroid disorders such as well-differentiated thyroid cancer. However, some extrathyroidal tissues also take up radioiodine, contributing to unwanted side effects of radioiodine therapy. Now that the molecule that mediates radioiodine uptake, the sodium iodide symporter (NIS), has been cloned and characterized, it may be possible to develop novel strategies to differentially modulate NIS expression and/or activity, enhancing it in target tissues and impeding it in others. In addition to restoring NIS expression/activity to ensure sufficient radioiodine uptake for the diagnosis and treatment of advanced thyroid cancers, we envision that it may be possible to selectively increase or confer NIS expression/activity in tumors of nonthyroidal tissues to facilitate the use of radioiodine in their diagnosis and treatment. We also consider the molecular basis of thyroid and nonthyroid disorders that may be complicated by NIS deregulation. Finally, we explore the use of NIS as an imaging reporter gene to monitor the expression profile of the transgene in transgenic mouse animal models and in patients undergoing gene therapy clinical trials.

Molecular imaging in living subjects: seeing fundamental biological processes in a new light

“…Examples of intracellular reporters include thymidine kinase, GFP, luciferase Contag et al 1997), cytosine deaminase, and tyrosinase (Weissleder et al 1997b), to name a few. Examples of reporters on or in the cell surface in the form of receptors include the dopamine 2 receptor (D2R) and receptors for somatostatin, transferrin (Moore et al 1998;Hogemann et al 2000), or the sodium iodide symporter (Boland et al 2000;Haberkorn et al 2001;Shen et al 2001;Cho et al 2002). Bogdanov et al (2000) have also constructed fusion proteins that act as "artificial receptors," consisting of a binding domain such as a peptide-based chelator that binds 99m…”

Salivary Gland Side Effects Commonly Develop Several Weeks After Initial Radioactive Iodine Ablation

“…Fortunately, the common mild salivary gland side effects (SSEs) (such as minor discomfort and swelling of the parotid and submandibular salivary glands or minor discomfort in the region of the thyroid bed) that develop within a day or two after RAI administration are almost always transient and rarely develop into significant clinical problems. However, even relatively low administered activities of RAI used for remnant ablation have been associated with the more clinically significant side effects of xerostomia, salivary gland pain and swelling, dry eyes, excessive tearing, or alterations in taste in as many as 20%230% of patients (7)(8)(9)(10). Fortunately, these side effects are usually transient but may persist in as many as 15% of patients (11,12).…”

Imaging of metastatic pulmonary tumors following NIS gene transfer using single photon emission computed tomography

“…In tissues where NIS protein is endogenously expressed, including the thyroid, [2][3][4] stomach, 5,6 salivary gland, [7][8][9] and lactating breast, 10,11 the accumulation of these radionuclides can be detected in vivo by nuclear imaging. Use of these radioisotopes has long been essential to the diagnosis and treatment of thyroid diseases, 12 and numerous studies have been conducted to investigate the use of NISmediated radionuclide accumulation in the diagnosis and treatment of nonthyroid malignancies.…”