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Noninvasive Imaging for Monitoring of Viable Cancer Cells Using a Dual-Imaging Reporter Gene

¹ Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea
² Department of Tumor Biology, Seoul National University College of Medicine, Seoul, Korea
³ Laboratory of Molecular Imaging and Therapy of Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Molecular imaging methods have been used recently to investigate biologic events. To develop a molecular imaging method suitable for monitoring viable cancer cells, we made a dual-imaging reporter gene system and examined the correlation between cancer cell number and signals from 2 reporter genes, sodium iodide symporter (NIS) and luciferase. Methods: NIS and luciferase genes were linked with the internal ribosomal entry site and transfected into SK-HEP1 cells to generate SK-HEP1-NL cells. ¹²⁵I uptake assays, luciferase assays, and scintigraphic and luminescence imaging were performed on SK-HEP1-NL cells. After treating with doxorubicin, cell counting, assays, and imaging were performed. SK-HEP1 and SK-HEP1-NL cells were inoculated subcutaneously into the flanks of nude mice. After incubation, scintigraphic and luminescence images were acquired and quantitated. Results: The results of radioiodide uptake, luciferase assay, and scintigraphic and luminescence imaging in vitro correlated well with viable cell numbers. Upon increasing the concentration of doxorubicin, cell numbers decreased, and this correlated with a decrease in radioactivity and luminescence intensity. The radioactivity from in vivo scintigraphic images and the intensity from luminescence images were also found to be proportional to the tumor weight. Conclusion: The developed dual-reporter imaging method using NIS and the luciferase gene reflected viable cancer cell numbers and could detect changes in cell number after doxorubicin treatment.

Key Words: reporter gene • sodium iodide symporter • luciferase • molecular imaging • drug development

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