Noninvasive Imaging of Cellular and Viral Therapies Using the NIS Reporter Gene

We are developing cellular therapies for a variety of applications and there is an urgent need to have convenient methods for noninvasive monitoring of these transplanted cells in preclinical animal models and in the patients enrolled in the clinical trials. NIS, the thyroidal sodium iodide symporter, is the reporter gene chosen for our virus, gene cell tracking applications. NIS is expressed endogenously in thyroid follicular cells where its role is to concentrate iodine for the synthesis of thyroid hormones. For more than 70 years, thyroidal NIS expression has been provided the basis for 123I gamma camera or SPECT/CT imaging in thyroid disorders. Using NIS imaging, we could monitor viral and cellular delivery to tumors or specific organs in the same animals serially over time out to 200 days. To determine the sensitivity of detection using our preclinical scanncer, MSC from rat, human and canine were collected from adipose tissues or the bone marrow, expanded and transduced with lentiviral vectors encoding the human or species specific NIS genes. NIS function in transduced MSC was first validated in vitro; NIS expressing MSC (MSC_NIS) from multiple species concentrated high levels of I-125 with no side effects. The sensitivity of cell detection was determined by transplanting a known number of MSC_NIS subcutaneously into mice. We can reliably detect 2x105 MSC_NIS in mice using the newly acquired U-SPECT II machine. Canine MSC derived from the bone marrow were surprisingly robust; viable cells were still detected (albeit lower numbers) at day 28 in the athymic mice. In contrast, NIS signals from adipose tissue derived rat or human MSC disappeared by day 7 post transplantation. Using PET imaging and F18-TFB, sensitivity of imaging could be significantly improved to detect lower numbers of cells. We are currently evaluating the use of NIS for tracking natural killer cells and transplanted hemapoietic stem cells and results will be presented.