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Correlation of Na⁺/I^– Symporter Expression and Activity: Implications of Na⁺/I^– Symporter as an Imaging Reporter Gene

¹ Integrated Biomedical Science Graduate Program, Ohio State University, Columbus, Ohio; ² Department of Physiology and Cell Biology, Ohio State University, Columbus, Ohio; ³ Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; and ⁴ Department of Internal Medicine, Ohio State University, Columbus, Ohio

Correspondence: For correspondence or reprints contact: Sissy M. Jhiang, PhD, 304 Hamilton Hall, 1645 Neil Ave., Ohio State University, Columbus, OH 43210. E-mail: jhiang.1{at}osu.edu

The Na⁺/I^– symporter (NIS) has been proposed as an imaging reporter gene to ascertain the expression of therapeutic genes in targeted tissues. In this study, we investigated whether posttranslational processing and cell-surface trafficking of NIS affect NIS-mediated radioiodide uptake in cells expressing exogenous NIS. Methods: We established FTC133, HeLa, and PC12 cell lines with doxycycline-inducible NIS expression to investigate the correlation among total NIS protein levels, cell-surface NIS protein levels, and NIS-mediated radioiodide uptake in cells induced with various levels of NIS. Results: We found that most exogenous NIS proteins were efficiently trafficked to the cell surface; thus, a possible deficiency in NIS cell-surface trafficking is not a concern for clinical applications of NIS gene transfer. The extent of radioiodide uptake correlated with cell-surface NIS protein level within a certain range, suggesting that the imaging signals can quantify levels of NIS expression only within a certain range in vivo. Finally, a moderate increase in NIS protein level significantly increased radioiodide uptake, indicating that a low level of NIS expression is sufficient to facilitate radionuclide imaging in vivo. Conclusion: Our study suggests that NIS will be useful as an imaging reporter gene to ascertain that the therapeutic gene is localized to the correct tissue and to monitor the expression levels and duration of the therapeutic gene.

Key Words: sodium iodide symporter • NIS • imaging reporter gene • cell-surface trafficking

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