Experimental targeted radioiodide therapy following transfection of the sodium iodide symporter gene: Effect an 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 cel l hosts. We observed perchlorate-inhibitable iodide uptake up to 41 fold ov er control in all NIS-transfected cells. We assessed the effect of NIS expr ession followed by exposure to I-131- on the clonogenic survival of UVW gli oma cells. After exposure of two-dimensional monolayer cultures of UVW-NIS culls to I-131- at a radioactive concentration of 4 MBq/mL, clonogenic surv ival was reduced to 21%. Similar treatment of UVW-NIS cells in three dimens ional spheroid cultures resulted in a reduction of clonogenic survival to 2 .5%. This increase in sensitivity to I-131 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 radiolog ical bystander effect plays a significant role in tumor cell sterilization.