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Development of a Sodium/Iodide Symporter (NIS)-Transgenic Mouse for Imaging of Cardiomyocyte-Specific Reporter Gene Expression

¹ Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea
² Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
³ Korean Institute of Radiological and Medical Sciences, Seoul, Korea

Development of a small animal imaging system for differentiated cell-specific reporter gene expression will enable us to image cellular differentiation in vivo. In this study, we developed a sodium/iodide symporter (NIS)-transgenic mouse in which NIS is constitutively expressed as an imaging reporter gene only in cardiomyocytes. Methods: To express NIS gene in cardiomyocytes, -myosin heavy chain (-MHC)-NIS was constructed and used for the production of NIS-transgenic mice. Twelve lines of positive founder were obtained. The adequacy of the transgenic mouse model was tested by in vivo scintigraphy, microPET, and a biodistribution study. Results: The myocardium of transgenic mice showed rapid and intense uptake of ¹³¹I, which was much higher than that of the thyroid, and also showed long retention by -camera pinhole imaging. The relative uptake ratio of the heart of transgenic mice was 4.6 ± 1.5, which was 3.8 ± 1.2 times higher than that of control wild-type mice. The uptake of the heart was completely blocked by oral administration of KClO₄, an NIS inhibitor. The heart of transgenic mouse was also clearly and intensely visualized on microPET using ¹²⁴I. Biodistribution data of these mice showed the uptake of 40–160 %ID/g (percentage injected dose per gram of tissue) of ^99mTc-pertechnetate in the heart compared with 40–60 %ID/g in the stomach, respectively. NIS expression in the myocardium was confirmed by immunohistochemistry using a NIS-specific antibody. Conclusion: We developed a transgenic mouse model to image cardiomyocytes with a -camera and microPET using an -MHC promoter and NIS. The transgenic mouse can be used as an imaging model for cardiomyocyte-specific reporter gene expression and cellular differentiation into cardiomyocytes after cardiac stem or progenitor cell transplantation.

Key Words: sodium/iodide symporter • transgenic mouse • reporter gene • nuclear imaging

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