Radioactive
iodine (RAI) is a key therapeutic modality for
thyroid cancer. Loss of RAI uptake in
thyroid cancer inversely correlates with patient's survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects.
Sodium iodide symporter (NIS) mediates
iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by
thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and
cancer thyroid cells, and we propose that several
reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in
thyroid cancer. Once validated in preclinical mouse models and clinical trials, these
reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of
thyroid cancer in terms of their
tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid
tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate
reagents to selectively increase RAI uptake in
thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of
thyroid cancer is yet to come in the near future.