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Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Gene Therapy volume 13, pages 60–66 (2006)Cite this article

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.

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Abbreviations

NIS:

sodium iodide symporter

CMV:

cytomegalovirus

MOI:

multiplicity of infection.

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Acknowledgements

The Prospect Creek Foundation provided the main source of funding for this work. Support was also received from the Mayo Foundation Breast Cancer grant, Prostate Cancer SPORE grant (CA91956) and the Mayo Breast Cancer Program.

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Authors and Affiliations

  1. Department of Endocrinology, Mayo Clinic, Rochester, MN, USA

    R M Dwyer, E R Bergert & J C Morris

  2. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    M K O'Connor

  3. Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, AZ, USA

    S J Gendler

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  1. R M Dwyer
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Correspondence to J C Morris.

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Dwyer, R., Bergert, E., O'Connor, M. et al. Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice. Gene Ther 13, 60–66 (2006). https://doi.org/10.1038/sj.gt.3302599

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