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  • br Conflicts of interest br Authors declare no conflicts of

    2020-08-18


    Conflicts of interest
    Authors declare no conflicts of interest.
    Acknowledgements
    This work was supported principally by the Department of Biotechnology (Bio-CARe scheme, BT/BioCARe/07/10003/2013-2014) to author Swati Biswas. 
    Appendix A. Supplementary data
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    Contents lists available at ScienceDirect
    Cancer Letters
    journal homepage: www.elsevier.com/locate/canlet
    Original Articles
    BIRC5 is a target for molecular imaging and detection of human pancreatic T cancer
    Shi-He Liua,b, Yeahwa Honga, Stephen Markowiaka, Robbi Sanchezd, Justin Creedena,b, John Nemunaitisc, Andrea Kalinoskia, James Willeyc, Paul Erhardte, Jason Leef,g,h, Michael van Damf,g,h, F. Charles Brunicardia,b,∗ a Department of Surgery, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA
    b Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA
    c Department of Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA
    d Department of Surgery, University of California Los Angeles, Los Angeles, CA, 90095, USA
    e Department of Pharmacology-Medicinal/Biological Chemistry, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA
    f Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, CA, 90095, USA
    g Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, 90095, USA
    h Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, 90095, USA
    Keywords:
    BIRC5
    Gaussia luciferase
    Pancreatic cancer
    Super promoter
    Thymidine kinase, microPET/CT imaging 
    Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer mortality with a dismal overall survival rate and an urgent need for detection of minute tumors. Current diagnostic modalities have high sensitivity and specificity for larger tumors, but not for minute PDAC. In this study, we test the feasibility of a precision di-agnostic platform for detecting and localizing minute human PDAC in mice. This platform includes: 1) defining BIRC5 as an early PDAC-upregulated gene and utilizing an enhanced BIRC5 super-promoter to drive expression of dual Gaussia luciferase (GLuc) and sr39 thymidine kinase (sr39TK) reporter genes exponentially and speci-fically in PDAC; 2) utilizing a genetically-engineered AAV2RGD to ensure targeted delivery of GLuc and sr39TK specifically to PDAC; 3) using serologic GLuc and sr39TK microPET/CT imaging to detect and localize minute human PDAC in mice. The study demonstrates feasibility of a precision diagnostic platform using an integrated technology through a multiple-stage amplification strategy of dual reporter genes to enhance the specificity and sensitivity of detection and localization of minute PDAC tumors and currently undetectable disease.