Radioiodine therapy targeting at hepatoma cells induced by transferring the human sodium/iodide symporter gene

Objective: Radioiodine has long been recognized as an effective therapy for abnormal tissue with human sodium/iodide symporter (hNIS) gene expression. In this study the authors investigated the feasibility of radioiodine therapy targeting hepatoma cells having transfected with hNIS gene and with murine albumin enhancer and promoter (mAlb) directed specific expression. Methods: For in vitro studies, hepatoma cells MH3924A were stably transfected with the recombinant retroviral vector, in which hNIS cDNA expression was driven by mAlb and coupled to hygromycin resistance gene using an internal ribosomal entry site (IRES). hNIS expression in hepatoma cells was evaluated by 125I uptake assay. For in vivo imaging studies, ACI rats bearing hepatoma were intravenously injected with 131I and imaged with small gamma camera. 131I biodistribution studies were carried out at 0.5, 1, 3, 6, 25 h respectively after 131I injection. Irradiation effects of 131I on hepatoma cells were estimated in vitro by calculating the survival rates of cultured cells and in vivo by the growth rates of grafted hepatoma. Results: 125I concentrations by stably transfected MH3924A cells in vitro were on average 240 folds higher than those of the wild type cells. After 7 h culture with 131I (3.7 MBq/ml), the survival rate of transfected cells decreased by 86% while of the wild cells by 8%. Intense 131I accumulations were seen at the transfected hepatoma foci after 131I administration but not at the untransfected hepatoma foci. Biodistribution data showed that, 3 h after 131I administration, 131I accumulation by transfected tumor tissues was 19.2 folds higher than that by non-transfected tumor. With positive 131I uptake, the transfected tumors had much slower growth rate than non-transfected tumors. Conclusions: Significant radioiodine uptake by hepatoma cells was demonstrated following hNIS gene transferring and expression both in vitro and in vivo. It was suggested that the hepatoma cells, if successfully transfected with hNIS gene, might be the target of radioiodine. (authors)