Experimental targeted radioiodide therapy following transfection of the sodium iodide symporter gene: effect on clonogenicity in both two-and three-dimensional models

To evaluate the potential of the expression of the sodium/iodide symporter (NIS) as a means of targeting radioiodine to tumor cells, we have employed plasmid-mediated transfection of the NIS gene into a range of mammalian cell hosts. We observed perchlorate-inhibitable iodide uptake up to 41-fold over control in all NIS-transfected cells. We assessed the effect of NIS expression followed by exposure to on the clonogenic survival of UVW glioma cells. After exposure of two-dimensional monolayer cultures of UVW–NIS cells to at a radioactive concentration of 4 MBq/mL, clonogenic survival was reduced to 21%. Similar treatment of UVW–NIS cells in three-dimensional spheroid cultures resulted in a reduction of clonogenic survival to 2.5%. This increase in sensitivity to exposure is likely to be due to a radiological bystander effect. These results are very encouraging for the development of a novel cytotoxic gene-therapy strategy in which a radiological bystander effect plays a significant role in tumor cell sterilization.