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Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy

Gene Therapy volume 11, pages 161–169 (2004)Cite this article

Abstract

The sodium iodide symporter (NIS) mediates iodide uptake into thyrocytes and is the molecular basis of thyroid radioiodine therapy. We previously have shown that NIS gene transfer into the F98 rat gliomas facilitated tumor imaging and increased survival by radioiodine. In this study, we show that: (1) the therapeutic effectiveness of 131I in prolonging the survival time of rats bearing F98/hNIS gliomas is dose- and treatment-time-dependent; (2) the number of remaining NIS-expressing tumor cells decreased greatly in RG2/hNIS gliomas post 131I treatment and was inversely related to survival time; (3) 8 mCi each of 125I/131I is as effective as 16 mCi 131I alone, despite a smaller tumor absorbed dose; (4) 188ReO4, a potent β− emitter, is more efficient than 131I to enhance the survival of rats bearing F98/hNIS gliomas. These studies demonstrate the importance of radiopharmaceutical selection, dose, and timing of treatment to optimize the therapeutic effectiveness of NIS-targeted radionuclide therapy following gene transfer into gliomas.

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Acknowledgements

We are indebted to our Nuclear Medicine colleagues of The Ohio State University Hospital, including Ms Bonnie Williams, Mr Cowan Edwards, Mr Aaron Haynam, and Ms Mary Morgan for their preparation of radionuclides and providing gamma camera assistance. We also thank Dr FF Russ Knapp at the Oak Ridge National Lab for his consultation regarding use of the 188Tungsten/188Rhenium generator. This work was partly supported by DOD Prostate Cancer Research Program DAMD 17-02-0119 (to SMJ), and the statistical analyses were supported by NIH Grant #MO1 RR00034 (to HNN via OSU GCRC).

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Authors and Affiliations

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

    DHY Shen, DK Marsee, J Schaap, J-Y Cho & SM Jhiang

  2. Department of Pathology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    W Yang & RF Barth

  3. Department of Radiology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    G Hinkle & RT Kloos

  4. Department of Statistics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    HN Nagaraja

  5. Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA

    RT Kloos & SM Jhiang

  6. Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC

    DHY Shen

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Shen, D., Marsee, D., Schaap, J. et al. Effects of dose, intervention time, and radionuclide on sodium iodide symporter (NIS)-targeted radionuclide therapy. Gene Ther 11, 161–169 (2004). https://doi.org/10.1038/sj.gt.3302147

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