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

Cancer Gene Ther. 2000 Dec;7(12):1529-36. doi: 10.1038/sj.cgt.7700264.


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 131I- on the clonogenic survival of UVW glioma cells. After exposure of two-dimensional monolayer cultures of UVW-NIS cells to 131I- 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 131I- 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / radiotherapy
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / radiotherapy
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes / therapeutic use*
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / radiotherapy*
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism
  • Neuroblastoma / radiotherapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / radiotherapy
  • Sodium Iodide / metabolism*
  • Symporters*
  • Thyroid Gland / metabolism
  • Transfection*
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / radiation effects
  • Tumor Stem Cell Assay


  • Carrier Proteins
  • Iodine Radioisotopes
  • Membrane Proteins
  • Symporters
  • sodium-iodide symporter
  • Sodium Iodide