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Pinhole micro-SPECT/CT for noninvasive monitoring and quantitation of oncolytic virus dispersion and percent infection in solid tumors

Gene Therapy volume 19, pages 279–287 (2012)Cite this article

Abstract

The purpose of our study was to validate the ability of pinhole micro-single-photon emission computed tomography/computed tomography (SPECT/CT) to: 1) accurately resolve the intratumoral dispersion pattern and 2) quantify the infection percentage in solid tumors of an oncolytic measles virus encoding the human sodium iodide symporter (MV-NIS). Sodium iodide symporter (NIS) RNA level and dispersion pattern were determined in control and MV-NIS-infected BxPC-3 pancreatic tumor cells and mouse xenografts using quantitative, real-time, reverse transcriptase, polymerase chain reaction, autoradiography and immunohistochemistry (IHC). Mice with BxPC-3 xenografts were imaged with 123I or 99TcO4 micro-SPECT/CT. Tumor dimensions and radionuclide localization were determined with imaging software. Linear regression and correlation analyses were performed to determine the relationship between tumor infection percentage and radionuclide uptake (% injected dose per gram) above background and a highly significant correlation was observed (r2=0.947). A detection threshold of 1.5-fold above the control tumor uptake (background) yielded a sensitivity of 2.7% MV-NIS-infected tumor cells. We reliably resolved multiple distinct intratumoral zones of infection from non-infected regions. Pinhole micro-SPECT/CT imaging using the NIS reporter demonstrated precise localization and quantitation of oncolytic MV-NIS infection, and can replace more time-consuming and expensive analyses (for example, autoradiography and IHC) that require animal killing.

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Acknowledgements

We thank our nuclear medicine technologist, Teresa D. Decklever (Mayo Clinic), for technical expertise and imaging assistance. This work was supported by the National Cancer Institute (Grant K08 CA103859, Grant P50 CA102701 and Grant R01 CA 125614).

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Authors and Affiliations

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

    A R Penheiter, G E Griesmann, M J Federspiel, D Dingli, S J Russell & S K Carlson

  2. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA

    M J Federspiel

  3. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    D Dingli & S J Russell

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

    S K Carlson

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  1. A R Penheiter
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Correspondence to S K Carlson.

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Penheiter, A., Griesmann, G., Federspiel, M. et al. Pinhole micro-SPECT/CT for noninvasive monitoring and quantitation of oncolytic virus dispersion and percent infection in solid tumors. Gene Ther 19, 279–287 (2012). https://doi.org/10.1038/gt.2011.107

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