1. ¹Iowa Cancer Research Foundation, Des Moines, IA, USA
2. ²Iowa State University, Ames, IA, USA

Correspondence: Dr E Mitrofanova, Iowa Cancer Research Foundation, 11043 Aurora Avenue, Urbandale, Iowa 50322, USA. E-mail: emitrofanova@iowacancer.org

Received 13 October 2005; Revised 21 January 2006; Accepted 29 January 2006; Published online 9 March 2006.

Abstract

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 ¹³¹I has minimal toxicity. The physical characteristics of ¹³¹I decay allow radiation penetration within a local area causing bystander killing of adjacent cells. Accumulation of ¹³¹I 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 ¹³¹I 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 ¹³¹I. We have also demonstrated 5–6-fold greater uptake of ¹²⁵I by rat NIS over human NIS in human cancer cells. Recently, we reported the capability of the rat NIS and ¹³¹I to effectively induce growth arrest of relatively large tumors (approximately 800 mm³) 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 ¹³¹I (one-third of the dose used in earlier reports). We also demonstrated that a higher concentration of ¹²³I 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-¹³¹I 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 ¹³¹I uptake.