Efficient gene delivery is a critical obstacle for gene therapy that must be overcome. Until current limits of gene delivery technology are solved, identification of systems with bystander effects is highly desirable. As an
anticancer agent, radioactive
iodine (131)I has minimal toxicity. The physical characteristics of (131)I decay allow radiation penetration within a local area causing bystander killing of adjacent cells. Accumulation of (131)I mediated by the
sodium iodide symporter (NIS) provides a highly effective treatment for well-differentiated
thyroid carcinoma. Other types of
cancer could also be treated by NIS-mediated concentration of lethal (131)I radiation in
tumor cells. Our group and others previously reported that a significant antitumor effect in mice was achieved after adenoviral delivery of rat or human NIS gene following administration of 3 mCi of (131)I. We have also demonstrated 5-6-fold greater uptake of (125)I by rat NIS over human NIS in human
cancer cells. Recently, we reported the capability of the rat NIS and (131)I to effectively induce growth arrest of relatively large
tumors (approximately 800 mm(3)) in an animal model. In the present work
tumor growth inhibition was achieved using adenoviral delivery of the rat NIS gene and 1 mCi of (131)I (one-third of the dose used in earlier reports). We also demonstrated that a higher concentration of (123)I was accumulated in the NIS-expressing
tumors than in the thyroid 20 min after radioiodine administration. The highest intratumoral radioiodine concentration was observed along the needle track; however, the rat NIS-(131)I effectively induced growth arrest of
tumor xenografts in mice through its radiological bystander effect. Importantly, the rat NIS allowed reducing the injected radioiodine dose by 70% with the same antitumor efficacy in pre-established
tumors. These results suggest that the rat NIS gene may be advantageous compared to the human gene in its ability to enhance intratumoral (131)I uptake.