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 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.
Department of Radiation Oncology, University of Glasgow, Scotland, UK. s.carlin@beatson.gla.ac.uk
S
S
Carlin
S H
SH
Cunningham
M
M
Boyd
A G
AG
McCluskey
R J
RJ
Mairs
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D012974:Sodium Iodide / Q000378:metabolism*; D027981:Symporters; D013961:Thyroid Gland / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D012974:Sodium Iodide; D027981:Symporters; D000099209:Sodium-Iodide Symporters