| The sodium iodide symporter (NIS) protein transports iodide into the thyroid. Transfection of NIS cDNA enables non-thyroidal cells to accumulate iodide. We used NIS expressing tumors to systemically concentrate 131I, then estimated the absorbed radioactive dose to the tumor, and correlated these doses to tumor responses. Image analysis with tracer doses could be used as prognostic indictor of response to therapeutic doses.; Tumors derived from either stable NIS transfected cells or adenoviral NIS (Ad-NIS) injected tumors derived from FaDu cells, were able to be visualized using several different imaging modalities. This demonstrated the ability to non-invasively image NIS function in tumors. The radioactivity detected in the NIS expressing tumors was higher in contralateral tumor and was quantified following imaging.; To correlate the estimated absorbed dose to therapeutic outcome, mice bearing stable NIS expressing tumors were given range of 131I from 0.1-1 mCi. To decrease inter-tumoral variability as observed in Ad-NIS delivery, we used stable NIS expressing tumors xenografts in athymic mice. The mice received 131I by i.p. injection when tumors reached ∼6 mm in diameter. The animals were imaged over time, and from the time activity curves, the estimated absorbed doses for each tumor were calculated. Tumors that received 6-25 Gy displayed growth delay, while tumors that received >25 Gy exhibited a significant regression in tumor size and complete remission for >90 days in 6 of 8 treated tumors.; To enhance therapeutic outcome two methods were used. To increase the tissue transduced, FaDu tumors were administered multiple injections of Ad-NIS on consecutive days followed by 131I. Dosimetry was estimated for the tumors and tumor responses were monitored and compared to those resulting from a single injection of Ad-NIS. 188ReO 4- was used to increase the dose delivered to the tumor. NIS expressing cells and tumors accumulated 188ReO4 - and were visualized by autoradiography and gamma camera scintigraphy respectively. Tumors that displayed higher estimated absorbed dose were compared to Ad-NIS tumors given 131I. Though multiple injections of Ad-NIS did not improve the therapeutic outcome, NIS expressing tumors treated with 188ReO4- could increase the absorbed dose enhancing tumor response. |
