Theranostic Studies of Human Sodium Iodide Symporter Imaging and Therapy Using (188)Re: A Human Glioma Study in Mice

OBJECTIVE: To investigate the role of (188)Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice. METHODS: The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of (188)Re were determined after incubating the cells with (188)Re. (188)Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with (188)Re were performed. U87-hNIS mediated (188)Re distribution, imaging and therapy in nude mice were also tested. RESULTS: U87-hNIS cell line was successfully established. The uptake of (188)Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated (188)Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to (188)Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased (188)Re retention even 48 hours after (188)Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm(3)) and control mice (861±153 mm(3)) treated with (188)Re for 4 weeks (P<0.01). CONCLUSION: The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific (188)Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by (188)Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept.