Radionuclide imaging and therapy in malignant melanoma after survivin promoter-directed sodium iodide symporter gene transfer in vitro and in vivo

摘要

This study aimed to develop a gene expression targeting method specific for the imaging and therapy of malignant melanoma A375 cells using the sodium iodide symporter gene under control of the survivin promoter (Ad-Sur-NIS). When compared to control Ad-Sur-GFP-treated cells, Ad-Sur-NIS resulted in significantly higher iodide uptake in all 50, 100, or 150 MOIs examined cells (P<0.001). In vitro clonogenic assay showed the inhibition rates induced by I were 94.8±12.4% in Ad-Sur-NIS, which was significantly higher than that in Ad-Sur-GFP infected cells (12.5±2.3%, P<0.001) or untreated cells (11.1±1.8%, P<0.001). In biodistribution studies, the tumor-to-muscle ratio in Ad-Sur-NIS infected tumors was higher than that in Ad-Sur-GFP infected tumors (16.34±4.43 vs 1.44±0.39, P<0.001). Moreover, mice that received the injection of Ad-Sur-NIS and I showed a significant delay in tumor growth. Taken together, Ad-Sur-NIS expresses functional NIS, resulting in intracellular accumulation of radionuclide in malignant melanoma A375 cells in vitro and in vivo.