In vitro and in vivo properties of a human anaplastic thyroid carcinoma cell line transfected with the sodium iodide symporter gene

To evaluate the feasibility of radionuclide gene therapy, we investigated the effect of sodium iodide symporter (NIS) gene transfection on the uptake of some beta- and gamma-emitters in human anaplastic thyroid cancer. NIS gene was transfected into human anaplastic cancer ARO cells using liposome (ARO-N) and its expression was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Iodide uptake by ARO-N was 109 times higher than by ARO, and Tc-99m and Re-188 uptake by ARO-N were 21 and 47 times higher than by ARO, respectively. The half-lives of radionuclides (I-125, Tc-99m, and Re-188) retention in the cells were about 12, 3 and 4 min, respectively. Biodistribution studies showed that ARO-N tumors accumulated higher amounts of radionuclides than ARO tumors. The mean accumulations of I-125, Tc-99m, and Re-188 in ARO-N tumors were 18.3 +/- 8.7, 14.6 +/- 7.1 and 23.2 +/- 3.5% injected dose per gram (ID/g) at 2 hours postinjection, respectively. Scintigraphic images of tumor bearing mice using I-131, Tc-99m, and Re-188 allowed clear visualization of ARO-N tumors. In summary, NIS gene transfection to a single anaplastic thyroid cancer cell line efficiently triggered high tumor uptake of radioiodines, Tc-99m and Re-188. These results demonstrate the possibility of imaging and therapy using NIS gene transfection in anaplastic thyroid carcinoma, although the short retention time is considered the major impediment to be resolved for the successful implementation.