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Tumor-Specific Targeting With Modified Sindbis Viral Vectors: Evaluation with Optical Imaging and Positron Emission Tomography In Vivo

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Abstract

Purpose

Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option.

Procedures

The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo.

Results

All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines.

Conclusion

We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.

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Acknowledgments

We thank the staff of the Radiochemistry/Cyclotron Core at MSKCC. Technical services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by NIH grants R24 CA83084 and P30 CA08748. Technical services provided by the MSKCC Small-Animal Imaging Core Facility were supported in part by the NIH (R24 CA83084 and P30 CA08748). Lars Stelter was supported by the Deutsche Forschungsgemeinschaft (Ste 1837/1-1). Steven M. Larson was supported by the Ludwig Center for Cancer Immunotherapy at MSKCC and the National Cancer Institute (P50-CA86483).

Conflict of Interest

The contents of this study are being used for a patent. According to the rules and regulations of New York University School of Medicine, if this patent is licensed by a third party, some of the authors (JT, BL, and DM) may receive benefits in the form of royalties or equity participation. All other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, USA

    Lars Stelter, Armen Torosjan, Valerie A. Longo, Nagavarakishore Pillarsetty, Pat Zanzonico & Steven M. Larson

  2. Department of Radiology, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Lars Stelter

  3. NYU Cancer Institute and the NYU GeneTherapy Center, Department of Pathology, NYU School of Medicine, New York University, New York, USA

    Jen-Chieh Tseng, Brandi Levin & Daniel Meruelo

  4. Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, USA

    Steven M. Larson

  5. Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, USA

    Steven M. Larson

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  1. Lars Stelter
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  2. Jen-Chieh Tseng
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Correspondence to Lars Stelter.

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Stelter, L., Tseng, JC., Torosjan, A. et al. Tumor-Specific Targeting With Modified Sindbis Viral Vectors: Evaluation with Optical Imaging and Positron Emission Tomography In Vivo . Mol Imaging Biol 15, 166–174 (2013). https://doi.org/10.1007/s11307-012-0585-8

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  • DOI: https://doi.org/10.1007/s11307-012-0585-8

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