Expression and activity of human Na+/I- symporter in human glioma cells byadenovirus-mediated gene delivery

Radioiodide concentrating activity in the thyroid, mediated by human Na+/I- symporter (hNIS), provides a mechanism for effective radioiodide treatment for patients who have invasive, recurrent, and metastatic thyroid cancers after total thyroidectomy. In an attempt to develop hNIS gene transfer for radioiodide therapy for patients with brain tumors, we have constructed rec ombinant adenoviruses, rAd-CMV-hNIS#9 and rAd-CMV-FLhNIS, to express exogen ous hNIS in U1240 and U1240Tag human glioma cells. U1240Tag differs from U1 240 glioma cells in that it expresses the SV40 large T antigen oncoprotein. In both U1240 and U1240Tag cells, radioiodide uptake (RAIU) activity in th e cells infected with rAd-CMV-hNIS#9 or rAd-CMV-FLhNIS increases as the ade noviral MOI increases. The protein expression profile of hNIS in infected c ells is generally in agreement with their RAIU activity profile. Although t he expressed hNIS#9 protein appeared to have a shorter half-life than FLhNI S, hNIS#9 expression could be maintained by multiple infections in these ce lls. In addition, we show that hNIS can be expressed and function in a xeno grafted human glioma by intratumoral injection of rAd-CMV-hNIS#9.