Imaging and antitumoral effect of a cyclo-oxygenase 2-specific replicative adenovirus for small metastatic gastric cancer lesions

Background: Long-term outcomes of patients with peritoneal dissemination of gastric cancer remain unsatisfactory despite advances in treatment modalities. Internal luminescence conditionally replicative adenovirus (CRAd) presents a novel approach for cancer treatment and imaging. Materials and Methods: 3CL is a modified cyclooxygenase- 2 (COX2) promoter-driven CRAd which contains the luciferase expression gene for bioluminescence imaging. The visualizing and therapeutic effect of 3CL was evaluated in a mouse model of peritoneal dissemination. Results: Intraperitoneal injection of 3CL achieved the shrinkage and reduction of lesions of peritoneal dissemination. Six model mice treated with 3CL had a significantly longer mean survival time than 6 mock-treated mice (85.7 versus 34.3 days, p=0.0005). By whole-body bioluminescent imaging, the sensitivity and specificity of peritoneal dissemination detection through macroscopic inspection were 58.1% and 83.2%, respectively, whereas 3CL viral imaging modality yielded corresponding values of 78.8% and 99.3%. Peritoneal lesions detected by imaging histologically contained cancer cells and necrotic tissue, which originated from viral oncolytic effects. Conclusion: Cox2 CRAds with 5/3 chimeric-fiber modification, therefore, appear to be a promising imaging and therapeutic tools for peritoneal dissemination of gastric cancer.