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Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK

Cancer Gene Therapy volume 12, pages 101–108 (2005)Cite this article

Abstract

In order to noninvasively detect Salmonella delivery vectors within tumors, we used a genetically modified Salmonella, VNP20009, that expresses the herpes simplex thymidine kinase (HSV1-tk) reporter gene. VNP20009-TK were able to selectively localize within murine tumor models and to effectively sequester a radiolabeled nucleoside analogue, 2′-fluoro-1-β-D-arabino-furanosyl-5-iodo-uracil (FIAU). A quantitative relationship between the level of radioactivity accumulated and the number of bacteria in tumor and different tissues was demonstrated. The in vivo accumulation of [14C]FIAU measured in tissue sample homogenates and sections were related to Salmonella number and to immunohistochemical bacterial staining, respectively. Quantitative autoradiography (QAR) revealed the relative intensity of [14C]FIAU accumulation in a tumor cross-section, demonstrating that the peripheral region of the tumor was significantly less active than internal regions. [124I]FIAU positron emission tomography (PET) and subsequent tissue radioactivity and bacterial concentration measurements were compared. A log–log relationship was found, and the PET images could identify multiple tumor sites. The ability to noninvasively detect Salmonella vectors by PET imaging has the potential to be conducted in a clinical setting, and could aid in development of these vectors by demonstrating the efficiency and duration of targeting as well as indicating the locations of tumors.

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Acknowledgements

We thank Terry Doyle, Ivan King, and Mario Sznol for helpful discussions. This work was supported by National Cancer Institute contract N01-CO-07102, NIH Grants P50 CA86438 and R24 CA83084, and Vion Pharmaceuticals, Inc.

Author information

Author notes

  1. Jeremy Pike

    Present address: Alexion Pharmaceuticals, Inc., 352 Knotter Drive, Cheshire, CT, 06410, USA

  2. Xiang Luo

    Present address: RibX Pharmaceuticals, Inc., 300 George St, Suite 301, New Haven, CT, 06511, USA

  3. Jacob D Runyan

    Present address: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 06877-0368, USA

  4. Julius Balatoni & Juri Gelovani Tjuvajev

    Present address: Dept. of Experimental Diagnostic Imaging, M. D. Anderson Cancer Center, Unit 057, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

Authors and Affiliations

  1. Departments of Neurology and Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, USA

    Surren A Soghomonyan, Michael Doubrovin, Julius Balatoni, Ronald Finn, Juri Gelovani Tjuvajev & Ronald Blasberg

  2. Vion Pharmaceuticals, Inc., 4 Science Park, New Haven, Connecticut, 06511, USA

    Jeremy Pike, Xiang Luo, Martina Ittensohn, Jacob D Runyan & David Bermudes

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  1. Surren A Soghomonyan
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Correspondence to Ronald Blasberg.

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Soghomonyan, S., Doubrovin, M., Pike, J. et al. Positron emission tomography (PET) imaging of tumor-localized Salmonella expressing HSV1-TK. Cancer Gene Ther 12, 101–108 (2005). https://doi.org/10.1038/sj.cgt.7700779

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