A preclinical large animal model of adenovirus-mediated expression of the sodium-iodide symporter for radioiodide imaging and therapy of locally recurrent prostate cancer

Roisin M. Dwyer, Stephen M. Schatz, Elizabeth R. Bergert, Rae M. Myers, Mary E. Harvey, Kelly L. Classic, Michael C. Blanco, Craig S. Frisk, Ronald J. Marler, Brian J. Davis, Michael K. O'Connor, Stephen J. Russell, John C. Morris

Research output: Contribution to journalArticle

Abstract

The sodium-iodide symporter (NIS) is primarily a thyroid protein, providing for the accumulation of iodide for biosynthesis of thyroid hormones. Native NIS expression has made possible the use of radioactive iodide to image and treat thyroid disease successfully. The current study, using adult male beagle dogs, was carried out in preparation for a Phase I clinical trial of adenovirus-mediated NIS gene (approved symbol SLC5A5) therapy for prostate cancer. Direct intraprostatic injection of virus (Ad5/CMV/NS) was followed by iv injection of 3 mCi123I and serial image acquisition. The dogs were then given a therapeutic dose of 131I (116 mCi/m2) and observed for 7 days. SPECT/CT fusion imaging revealed clear images of the NIS-transduced prostates. Dosimetry calculations revealed an average absorbed dose to the prostate of 23 ± 42 cGy/mCi 131I, with acceptably low radiation doses to other organs. This study demonstrated the successful introduction of localized NIS expression in the prostate gland of dogs, with no vector-related toxicity observed. None of the animals experienced any surgical complications, and serum chemistry panels showed no significant change following therapy. The results presented provide further evidence of the safety and efficacy of NIS as a therapeutic gene and support translation of this work into the clinical setting.

Original languageEnglish (US)
Pages (from-to)835-841
Number of pages7
JournalMolecular Therapy
Volume12
Issue number5
DOIs
StatePublished - Nov 2005

Keywords

  • Adenovirus
  • Gene therapy
  • Prostate cancer
  • Radioiodine
  • Sodium iodide symporter

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Dwyer, R. M., Schatz, S. M., Bergert, E. R., Myers, R. M., Harvey, M. E., Classic, K. L., Blanco, M. C., Frisk, C. S., Marler, R. J., Davis, B. J., O'Connor, M. K., Russell, S. J., & Morris, J. C. (2005). A preclinical large animal model of adenovirus-mediated expression of the sodium-iodide symporter for radioiodide imaging and therapy of locally recurrent prostate cancer. Molecular Therapy, 12(5), 835-841. https://doi.org/10.1016/j.ymthe.2005.05.013