Radioiodine Gene Therapy of Hepatocellular Carcinoma Targeted Human Alpha Fetoprotein

Introduction: We conducted a molecular imaging and gene therapy method in alpha-fetoprotein (AFP)-producing hepatocellular carcinoma (HCC) by tumor-specfic expression of the human sodium/iodide symporter (hNIS) using an AFP promoter. Methods: The tumor-specific expression of hNIS gene by the AFP enhancer/promoter was constructed as pcDNA3-AFP/hNIS. The pcDNA3-AFP/hNIS was stably transfected to human HCC (Huh-7/AN) and rat glioma cells (C6/AN). Functional hNIS expression was confirmed by radioiodine uptake. The mRNA and protein-expression level of hNIS were measured. Biodistribution of I-131 was evaluated, and scintigraphic images of Tc-99m were obtained in xenografted mice. A clonogenic assay was performed by I-131. And, the in vivo therapeutic effect of I-131 was evaluated in xenografted mice. Results: In Huh-7/AN cells, iodine was highly accumulated and completely blocked by perchlorate. The protein and mRNA expression levels were correlated with iodine uptake. Radioiodine uptake in Huh-7/AN tumors was higher than those of control tumors and clearly visualized. The survival rate was significantly decreased in Huh-7/AN cells by I-131. Moreover, a growth of Huh-7/AN tumors was inhibited by 1311 in mice. Conclusions: AFP-producing hepatoma can be targeted and treated with radionuclides and hNIS, using AFP enhancer/promoter. This targeted hNIS gene therapy and molecular imaging have the potential to be used in the management of AFP-producing HCC.