BIRC5 is a target for molecular imaging and detection of human pancreatic cancer

Cancer Lett. 2019 Aug 10:457:10-19. doi: 10.1016/j.canlet.2019.04.036. Epub 2019 May 3.


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 diagnostic 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 specifically 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.

Keywords: BIRC5; Gaussia luciferase; Pancreatic cancer; Super promoter; Thymidine kinase, microPET/CT imaging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / diagnostic imaging*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Feasibility Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • Mice, Nude
  • Molecular Imaging*
  • Optical Imaging*
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Positron Emission Tomography Computed Tomography*
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Survivin / genetics
  • Survivin / metabolism*
  • Thymidine Kinase / genetics
  • Thymidine Kinase / metabolism
  • Tumor Burden
  • Up-Regulation
  • X-Ray Microtomography*


  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Survivin
  • Luciferases
  • Thymidine Kinase