Original Article
Gene Therapy (2006) 13, 60–66. doi:10.1038/sj.gt.3302599; published online 25 August 2005
Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice
R M Dwyer1, E R Bergert1, M K O'Connor2, S J Gendler3 and J C Morris1
- 1Department of Endocrinology, Mayo Clinic, Rochester, MN, USA
- 2Department of Radiology, Mayo Clinic, Rochester, MN, USA
- 3Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ, USA
Correspondence: Dr JC Morris, Department of Endocrinology and Internal Medicine, 200 First Street SW, Rochester, MN 55905, USA. E-mail: morris.john@mayo.edu
Received 3 March 2005; Revised 24 May 2005; Accepted 8 July 2005; Published online 25 August 2005.
Abstract
Ovarian cancer represents the fifth leading cause of cancer death among women in the United States, with >16 000 deaths expected this year. This study was carried out to investigate the potential of sodium iodide symporter (NIS)-mediated radioiodide therapy as a novel approach for ovarian cancer treatment. Radioiodide is routinely and effectively used for the treatment of benign and malignant thyroid disease as a result of native thyroidal expression of NIS, which mediates iodide uptake. In vitro gene transfer studies in ovarian cancer cells revealed a 12- and five-fold increase in iodide uptake when transduced with Ad/CMV/NIS or Ad/MUC1/NIS, respectively. Western blot/immunohistochemistry confirmed NIS protein expression. In vivo ovarian tumor xenografts were infected with the adenoviral constructs. 123I imaging revealed a clear image of the CMV/NIS-transduced tumor, with a less intense image apparent following infection with MUC1/NIS. Therapeutic doses of 131I following CMV/NIS infection caused a mean 53% reduction in tumor volume (P<0.0001). MUC1/NIS-transduced tumors did not regress, although at 8 weeks following therapy, tumor volume was significantly less that of control animals (166 versus 332%, respectively, P<0.05). This study represents a promising first step investigating the potential for NIS-mediated radioiodide imaging and therapy of ovarian tumors.
Keywords:
sodium iodide symporter, MUC1, radioiodine, ovarian cancer
Abbreviations:
NIS, sodium iodide symporter; CMV, cytomegalovirus; MOI, multiplicity of infection.
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