Genetically targeted radiotherapy of head and neck squamous cell carcinoma using the sodium-iodide symporter (NIS).

Abstract

Gene therapy that uses delivery of the sodium-iodide symporter (NIS) gene followed by radioiodide administration has been proposed as a novel form of radiotherapy for nonthyroidal cancers. In vitro [(125)I] iodide accumulation and efflux from cells was determined after treatment with an NIS-expressing adenovirus (Ad-NIS). A clonogenic survival assay and tumor growth experiment that used athymic mice were used to demonstrate the in vitro and in vivo cytotoxicity of Ad-NIS treatment and [(131)I] iodide delivery. Head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-NIS exhibit significant amounts of radioiodide accumulation and retention. In vitro HNSCC cell survival was significantly diminished after NIS gene delivery followed by administration of [(131)I] iodide. Moreover, NIS gene transfer/[(131)I] iodide administration dramatically attenuated HNSCC tumor formation in athymic mice. Our data demonstrate the feasibility of genetically targeted radiotherapy by use of the NIS gene as a possible therapeutic intervention in head and neck cancer.