Engineering Oncolytic Vaccinia Viruses for Non-Invasive Optical Imaging of Tumors

Attenuated vaccinia viruses (VV) selectively replicate in malignant cells and confer oncolytic effect in vivo. Here we demonstrate that oncolytic VV may also be used as a diagnostic agent for tumor-bearing mice. A series of re- combinant vaccinia viruses has been constructed expressing optical reporters to mediate emission of bioluminescent and fluorescent light which can be visualized. Data show that following systemic virus delivery the developing tumors can be non-invasively visualized in mice in vivo. Renilla luciferase and Aquoria GFP have been effective in imaging xenografted PC-3 prostate and orthotopic MB-49 bladder tumors. Brighter reporters, Gaussia luciferase and Renilla GFP have been used for imaging TRAMP prostate cancer and C6 subcutaneous model of glioma. The C6 imaging data have been corroborated by traditional MRI. We are also developing a VV-mediated system for tumor detection in far red or near infra red fluorescent light. Results suggest that VV-mediated imaging is a promising alternative for early diagnosis of various human cancers.