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Imaging of metastatic pulmonary tumors following NIS gene transfer using single photon emission computed tomography

Cancer Gene Therapy volume 11, pages 121–127 (2004)Cite this article

Abstract

The Na+/I− symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine into thyroid follicular cells. Recently, we and others have demonstrated the feasibility of imaging subcutaneous xenografts expressing exogenous NIS, suggesting that NIS may serve as an imaging reporter gene to monitor vector delivery and therapeutic gene expression. In this study, we established NIS-expressing pulmonary tumors in nude mice to investigate the minimal tumor size required for in vivo detection of pulmonary tumors by single photon emission computed tomography (SPECT) with pinhole collimation. In order to define the anatomic location of NIS-expressing tumor nodules detectable by SPECT, we performed simultaneous, dual-isotope imaging. We injected 1 mCi 99mTc-MAA via tail vein to image pulmonary perfusion and injected 1 mCi Na125I intraperitoneally to image NIS-expressing tumors. Fused images showed that 99mTc-MAA perfusion defects correlated with NIS-mediated 125I uptake. Post-mortem analysis revealed that tumors 3 mm in diameter could be detected by SPECT with pinhole collimation. These studies demonstrate the feasibility of SPECT to detect pulmonary tumors expressing exogenous NIS in mice.

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Acknowledgements

We thank our colleagues in the Division of Nuclear Medicine, including Ms Bonnie Williams, Mr Cowan Edwards, and Mr Aaron Haynam for the preparation of radionuclides. In addition, we also thank Dr W Yang for his assistance with tail vein injections. This work was supported by DOD Prostate Cancer Research Program DAMD 17-02-0119 (to SMJ) and by the NIH T32 DE14320 from the National Institute of Dental and Craniofacial Research (to DKM).

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Authors and Affiliations

  1. Medical Scientist Program, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA

    Derek K Marsee

  2. Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA

    Daniel H Y Shen, Douangsone D Vadysirisack, Xiaoqin Lin & Sissy M Jhiang

  3. Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, ROC

    Daniel H Y Shen & Richard T Kloos

  4. Division of Photon Imaging, Gamma Medica, Inc., Northridge, 91324, California, USA

    Lawrence R MacDonald

  5. Department of Radiology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA

    George Hinkle

  6. Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA

    Richard T Kloos & Sissy M Jhiang

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  1. Derek K Marsee
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  2. Daniel H Y Shen
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Correspondence to Sissy M Jhiang.

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Marsee, D., Shen, D., MacDonald, L. et al. Imaging of metastatic pulmonary tumors following NIS gene transfer using single photon emission computed tomography. Cancer Gene Ther 11, 121–127 (2004). https://doi.org/10.1038/sj.cgt.7700661

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