Determination of the optimal time for radioiodine therapy in anaplastic thyroid carcinoma using the adenovirus-mediated transfer of sodium iodide symporter gene

Abstract

Gene therapy using human sodium iodide symporter (hNIS) and radioiodine has been considered promising in a variety of gene therapy trials. However, the optimal timing of radioiodine application following hNIS gene transfer remains unknown. The present study aimed to investigate the serial expression of hNIS following adenovirus-mediated hNIS gene transfer into anaplastic thyroid carcinoma (ARO) to determine the optimal timing of radioiodine application. Recombinant adenovirus encoding the hNIS gene (rAd-hNIS) was generated using a homologous recombination reaction. The iodine uptake of rAd-hNIS‑transfected ARO cells gradually increased until 120min post‑125I application but the fold increase, reflecting the relative uptake of rAd-hNIS‑transfected compared to non‑transfected ARO cells, reached plateau at 60min post‑125I application. For the invivo analysis, rAd-hNIS was injected intratumorally into ARO cell xenografts in the thighs of nude mice (n=12). Two, 3, 4 and 6days after rAd-hNIS injection, γ‑scintigraphic images were obtained 60min following injection of 5.5MBq of 131I intraperitoneally. Treated/non-treated (T/NT) xenograft count ratios were the highest at day2 post‑rAd-hNIS injection (2.85±0.61), and gradually decreased thereafter (2.54±0.65, 2.31±0.42 and 2.18±0.90 at days3, 4 and6 post‑rAd-hNIS injection, respectively). Real‑time polymerase chain reaction (RT-PCR) and immunohistochemical staining demonstrated that hNIS expression was the highest at day2 following rAd-hNIS injection. In conclusion, the optimal timing for radioiodine administration is day 2 after adenovirus-mediated hNIS gene transfer into anaplastic thyroid carcinoma.