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In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas

Gene Therapy volume 9, pages 1139–1145 (2002)Cite this article

Abstract

Radioactive iodide uptake (RAIU) in thyroid follicular epithelial cells, mediated by the sodium iodide symporter (NIS), is the first rate-limiting step in iodide accumulation which provides a mechanism for effective radioiodide treatment for patients with thyroid cancer. We hypothesize that NIS gene transfer to non-thyroid tumor cells will enhance intracellular radioiodide accumulation and result in better tumor control. Here, we performed non-invasive tumor imaging and 131I therapy studies using rats bearing intracerebral F98 gliomas that have been retrovirally transduced with human NIS. Our results show that: (1) NIS is expressed in the intracerebral F98/NIS gliomas; (2) F98/NIS gliomas can be imaged by 99mTcO4 (whose uptake is also mediated by NIS) and 123I scintigraphy; (3) significant amounts of radioiodide were retained in the tumors at 24 h after 123I injection; (4) RAIU and NIS expression in the thyroid gland can be reduced by feeding a thyroxine-supplemented diet; and (5) survival time was increased in rats bearing F98/hNIS tumors by 131I treatment. These studies warrant further investigating tumor imaging and therapeutic strategies based on NIS gene transfer followed by radioiodide administration in a variety of human cancers.

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Acknowledgements

We thank Dr Kathleen Boris-Lawrie for providing the pLXSN retroviral vector, Mr Steve Lefevre for preparation of radionuclides, and Ms Danielle Westfall for assistance with animal handling.

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Authors and Affiliations

  1. Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH, USA

    J-Y Cho, D HY Shen, T LF Buckwalter & S M Jhiang

  2. Department of Pathology, The Ohio State University, Columbus, OH, USA

    W Yang & R F Barth

  3. Department of Radiology, The Ohio State University, Columbus, OH, USA

    B Williams, G Hinkle & R Pozderac

  4. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA

    K MD La Perle

  5. Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

    R Kloos

  6. Department of Statistics, The Ohio State University, Columbus, OH, USA

    H N Nagaraja

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Cho, JY., Shen, D., Yang, W. et al. In vivo imaging and radioiodine therapy following sodium iodide symporter gene transfer in animal model of intracerebral gliomas. Gene Ther 9, 1139–1145 (2002). https://doi.org/10.1038/sj.gt.3301787

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  • DOI: https://doi.org/10.1038/sj.gt.3301787

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