Monitoring of tumor progression using bioluminescence imaging in a nude mice orthotopic model of human small cell lung cancer

Abstract

Introduction Lung cancer is the main cause of cancer death throughout the world and a clinically relevant animal model of human small cell lung carcinoma (SCLC) should be useful to study the molecular aspects of the tumor progression and test the efficiency of new therapeutic agents. In this study, we generated a reproductible and reliable nude mice orthotopic model of human SCLC based on NCI-H209 tumor cells genetically modified to express firefly luciferase. Methods NCI-H209 cells were transfected with pCMV-luc plasmid and clones highly expressing luciferase were isolated and amplified. Cells were analyzed for long-term bioluminescent stability and a clone was subcutaneously passaged twice in vivo to enhance tumorigenicity. Cells resuspended in Matrigel ® and/or EDTA RPMI medium containing a Tc 99M colloid were implanted intrabronchially using a catheter inserted into the trachea and positioned into the right main bronchus using interventional imaging. Punctual deposition of cells was then assessed by scintigraphy. Tumor progression was then followed using bioluminescence imaging. Results Only tumor nodules were observed into lung and trachea when cells were implanted with EDTA Lung tumor invading parenchyma were present in 40% of the mice with Matrigel ® and improved to 75% with EDTA and Matrigel ® . The growth of the primary tumor was sensitively and non-invasively followed and quantified by bioluminescence imaging using a CCD-camera. This tool allows a real-time monitoring of tumor progression on the same animals over a 2-12 week period. Combination of 3D bioluminescence imaging and computed tomography scanning was used to further document tumor location and measurement. Subsequently, the histological analysis of tissue sections confirmed the presence of a lung tumor. Conclusion Our nude mice orthotopic model resembles various stages human small cell lung carcinoma, and then could be useful for evaluating new therapeutic strategies.