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

Molecular imaging methods have been used recently to inves-tigate 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 scin-tigraphic 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 lu-minescence 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 lumines-cence 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 can-cer cell numbers and could detect changes in cell number after doxorubicin treatment. Key Words: reporter gene; sodium iodide symporter; luciferase; molecular imaging; drug developmen