1. ¹Department of Endocrinology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2. ²Department of Urology, Mayo Clinic, Rochester, MN 55905, USA
3. ³Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905, USA
4. ⁴Radiation Safety, Mayo Clinic, Rochester, MN 55905, USA
5. ⁵Department of Comparative Medicine, Mayo Clinic, Rochester, MN 55905 USA
6. ⁶Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, USA
7. ⁷Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
8. ⁸Department of Radiology, Mayo Clinic, Rochester, MN 55905 USA

Correspondence: John C. Morris, Department of Endocrinology and Internal Medicine, 200 First Street SW, Rochester, MN 55905, USA. E-mail: morris.john@mayo.edu

Received 25 February 2005; Revised 10 May 2005; Accepted 29 May 2005.

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 mCi ¹²³I 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.