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In vivo imaging system in detecting expression and distribution of replication-deficient adenovirus carrying luciferase in mice
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Abstract:
Objective : To study the expression of luciferase in mice delivered by replication-deficient adenovirus carrying luciferase (Ad-luciferase, Ad-Luci) through different injection routes, so at to provide information for adenovirus-mediated tumor gene therapy. Methods: Nude mouse model bearing human pancreatic cancer PANC-1 cells was established and Ad-Luci was administered into transplanted tumors with single or multiple intratumoral injections. Ad-Luci was also administered into normal mice through intramuscular, intravenous and intraperitoneal injections. The distribution and expression of luciferase in mice were monitored by in vivo IVIS Lumina imaging system and the toxicity of Ad-Luci was also studied. Results: Single intratumoral injection of Ad-Luci resulted in continuous luciferase expression for at least 15 d, while multiple injections resulted in even longer expression. Intramuscular injection of Ad-Luci gave a weaker and shorter duration of luciferase expression for no longer than 48 h. The majority of Ad-Luci injected through tail-vein homed to liver and expressed luciferase for at least 18 d. Expression of luciferase by intraperitoneal injection decreased with time-lapse and lasted for about 7 d. No significant toxic reactions were observed in all groups during the study. Conclusion: Intratumoral injection of adenovirus carrying exogenous gene gives a continuous expression of gene for a long duration, while multiple injections result in even longer expression; liver is the main target organ after tail intravenous administration and provides long expression duration.
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Project supported by the National High Science and Technology Research and Development Program (863 Program) of China (No. 2007AA021001), and the National Natural Science Foundation of China (No. 30772527)
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