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 language | English (US) |
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Pages (from-to) | 835-841 |
Number of pages | 7 |
Journal | Molecular Therapy |
Volume | 12 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2005 |
Keywords
- Adenovirus
- Gene therapy
- Prostate cancer
- Radioiodine
- Sodium iodide symporter
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Genetics
- Pharmacology
- Drug Discovery