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Imaging of human sodium-iodide symporter gene expression mediated by recombinant adenovirus in skeletal muscle of living rats

  • Molecular Imaging
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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

We evaluated the feasibility of non-invasive imaging of recombinant adenovirus-mediated human sodium-iodide symporter (hNIS) gene expression by 99mTcO4 − scintigraphy in skeletal muscle of rats.

Methods

Replication-defective recombinant adenovirus encoding hNIS gene [Rad-CMV-hNIS 5×107, 2×108 or 1×109 plaque forming units (pfu)] or β-galactosidase gene (Rad-CMV-LacZ 1×109 pfu) was injected into the right biceps femoris muscle of rats (n=5–6 for each group). Three days after gene transfer, scintigraphy was performed using a gamma camera 30 min after injection of 99mTcO4 − (1.85 MBq). An additional two rats injected with 1×109 pfu of Rad-CMV-hNIS underwent 99mTcO4 − scintigraphy with sodium perchlorate. After the imaging studies, rats were sacrificed for assessment of the biodistribution of 99mTcO4 − and measurement of hNIS mRNA expression.

Results

In all the rats injected with 1×109 pfu of Rad-CMV-hNIS, hNIS expression was successfully imaged by 99mTcO4 − scintigraphy, while rats injected with Rad-CMV-LacZ or lower doses of Rad-CMV-hNIS failed to show uptake. The biodistribution studies indicated that a significantly different amount of 99mTcO4 − was retained in the liver (p<0.001) and the right muscle (p<0.05), with the highest uptake in rats injected with 1×109 pfu of Rad-CMV-hNIS. The muscular hNIS mRNA level quantified by real-time reverse transcription-polymerase chain reaction was significantly higher in rats injected with 1×109 pfu of Rad-CMV-hNIS (p<0.05), with a positive correlation with the imaging counts (r=0.810, p<0.05) and the biodistribution (r=0.847, p<0.001). Hot spots in rats injected with 1×109 pfu of Rad-CMV-hNIS were specifically inhibited by sodium perchlorate.

Conclusion

This study illustrated that 99mTcO4 − scintigraphy can monitor Rad-CMV-hNIS-mediated gene expression in skeletal muscle of rats, non-invasively and quantitatively.

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Acknowledgements

We are grateful to Sissy M. Jhiang (Department of Physiology, Ohio State University, Ohio, USA) for generously providing recombinant adenoviral-human sodium-iodide symporter gene. We also wish to thank Kyong-Rye Dong, and Joon-Hong Cheon (Department of Nuclear Medicine, Asan Medical Center, Seoul, Korea) for their skilful technical assistance in nuclear imaging. This study was supported by a grant (02-287) from the Asan Institute for Life Sciences, Seoul, Korea.

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Authors and Affiliations

  1. Department of Internal Medicine (Cardiology), Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736, South Korea

    Hyun Suk Yang & Seong-Wook Park

  2. Department of Microbiology, University of Ulsan College of Medicine, Seoul, South Korea

    Heuiran Lee & Sung ** Kim

  3. Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea

    Won Woo Lee

  4. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Won Woo Lee, You-Jung Yang & Dae Hyuk Moon

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  1. Hyun Suk Yang
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Correspondence to Seong-Wook Park.

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Yang, H.S., Lee, H., Kim, S.J. et al. Imaging of human sodium-iodide symporter gene expression mediated by recombinant adenovirus in skeletal muscle of living rats. Eur J Nucl Med Mol Imaging 31, 1304–1311 (2004). https://doi.org/10.1007/s00259-004-1570-5

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