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A steep radioiodine dose response scalable to humans in sodium-iodide symporter (NIS)-mediated radiovirotherapy for prostate cancer

Cancer Gene Therapy volume 19, pages 839–844 (2012)Cite this article

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Abstract

The sodium-iodide symporter (NIS) directs the uptake and concentration of iodide in thyroid cells. We have extended the use of NIS-mediated radioiodine therapy to prostate cancer. We have developed a prostate tumor specific conditionally replicating adenovirus that expresses hNIS (Ad5PB_RSV-NIS). For radiovirotherapy to be effective in humans, the radioiodine dose administered in the pre-clinical animal model should scale to the range of acceptable doses in humans. We performed 131I dose-response experiments aiming to determine the dose required in mice to achieve efficient radiovirotherapy. Efficacy was determined by measuring tumor growth and survival times. We observed that individual tumors display disparate growth rates that preclude averaging within a treatment modality indicating heterogeneity of growth rate. We further show that a statistic and stochastic approach must be used when comparing the effect of an anti-cancer therapy on a cohort of tumors. Radiovirotherapy improves therapeutic value over virotherapy alone by slowing the rate of tumor growth in a more substantial manner leading to an increase in survival time. We also show that the radioiodine doses needed to achieve this increase scaled well within the current doses used for treatment of thyroid cancer in humans.

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Acknowledgements

We thank Tracy Decklever at the Nuclear Medicine Animal Imaging Resource Mayo Clinic, Rochester for technical help and Dr David Dingli at the Department of Molecular Medicine, Mayo Clinic, Rochester, MN, for helpful discussion. This work was supported by Prostate SPORE Grant P50 CA 091956, Donald J Tindall, PI, John C Morris, Project Director.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, MN, USA

    M A Trujillo, S McDonough & J C Morris

  2. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA

    M J Oneal

  3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    R Qin

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  1. M A Trujillo
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Correspondence to J C Morris.

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Trujillo, M., Oneal, M., McDonough, S. et al. A steep radioiodine dose response scalable to humans in sodium-iodide symporter (NIS)-mediated radiovirotherapy for prostate cancer. Cancer Gene Ther 19, 839–844 (2012). https://doi.org/10.1038/cgt.2012.68

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