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Radiation-Guided P-Selectin Antibody Targeted to Lung Cancer

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Abstract

Purpose: P-selectin expression is significantly increased in tumor microvasculature following exposure to ionizing radiation. The purpose of this study was to image radiation-induced P-selectin expression in vivo using optical imaging and gamma camera imaging in a heterotopic lung cancer model by using ScFv antibodies to P-selectin. Procedures: In vitro studies using endothelial cells were done using 3 Gy radiation and selected ScFv antibodies to P-selectin. In vivo studies were performed using Lewis lung carcinoma cells subcutaneously injected into the hind limbs of nude mice. Mice were treated with 6 Gy radiation and sham radiation 10 days post-inoculation. P-selectin expression was assessed with near-infrared imaging using Cy7 labeled antibody, and gamma camera imaging using 111In-DTPA labeled antibody. Results: In vitro studies showed antibody binding to P-selectin in radiation treated endothelial cells. In vivo optical imaging and gamma camera imaging studies showed significant tumor-specific binding to P-selectin in irradiated tumors compared to unirradiated tumors. Conclusions: Optical imaging and gamma camera imaging are effective methods for visualizing in vivo targeting of radiation-induced P-selectin in lung tumors. This study suggests that fluorescent-labeled and radiolabeled ScFv antibodies can be used to target radiation-induced P-selectin for the tumor-specific delivery of therapeutic drugs and radionuclides in vivo.

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Acknowledgments

This work was supported in part by National Cancer Institute grants R01-CA1256757, R21-CA128456, R01-CA112385, P30-CA68485, the Ingram Charitable Trust, and the Vanderbilt-Ingram Cancer Center. The research of Todd E. Peterson, Ph.D. was supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    G. Hariri, Y. Zhang, A. Fu, Z. Han & D. Hallahan

  2. National Cancer Institute, Center for Cancer Research, Bethesda, MD, 20892, USA

    M. Brechbiel

  3. Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, 37232, USA

    M. N. Tantawy & T. E. Peterson

  4. Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, 37232, USA

    R. Mernaugh & D. Hallahan

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  1. G. Hariri
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  2. Y. Zhang
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  3. A. Fu
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Correspondence to D. Hallahan.

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Hariri, G., Zhang, Y., Fu, A. et al. Radiation-Guided P-Selectin Antibody Targeted to Lung Cancer. Ann Biomed Eng 36, 821–830 (2008). https://doi.org/10.1007/s10439-008-9444-9

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