Research Article

Gene Therapy (2004) 11, 161–169. doi:10.1038/sj.gt.3302147

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

DHY Shen1,6, DK Marsee1, J Schaap1, W Yang2, J-Y Cho1, G Hinkle3, HN Nagaraja4, RT Kloos3,5, RF Barth2 and SM Jhiang1,5

  1. 1Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
  2. 2Department of Pathology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
  3. 3Department of Radiology, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
  4. 4Department of Statistics, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
  5. 5Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA
  6. 6Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC

Correspondence: Dr SM Jhiang, Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210-1218, USA

Received 14 April 2003; Accepted 25 July 2003.

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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 beta- 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.

Keywords:

sodium iodide symporter, radionuclide therapy, brain neoplasm

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