Noninvasive of adenovirus tumor retargeting in living subjects by a soluble adenovirus receptor-epidermal growth factor (sCAR-EGF) fusion protein

Purpose: To demonstrate that non-invasive bioluminescent imaging can monitor restricted expression from a nonreplicating adenovirus in which the cyclooxygenase-2 (COX-2) promoter drives firefly luciferase. Procedures: Adenovirus in which the COX-2 promoter drives the firefly luciferase imaging gene was injected intratumorally into xenografts that express relatively low and relatively high levels of COX-2. Adenovirus that expresses Renilla Luciferase from the cytomegalovirus early promoter was co-injected, to normalize for injection, leakage, vascularization, etc. COX-2 restricted firefly luciferase and global Renilla Luciferase activities were measured by optical imaging techniques both in vivo and in isolated tissues. Results: Dramatic reduc tion in hepatic luciferase expression after intravenous viral injection can be imaged non-invasively in living animals. Following intratumoral injection, luciferase levels in tumor xenografts that express differing endogenous COX-2 levels reflect the luciferase levels observed when these cells are infected in cell culture. Essentially no luciferase expression is observed in liver following intratumoral injection. Conclusion: Both tissue restricted exp ression and transcriptional redirection to tumors expressing COX-2 can be imaged non-invasively following injection of Adenovirus expressing firefly luciferase from the COX-2 promoter.