In vivo bioluminescence imaging for early detection and monitoring of disease progression in a murine model of neurobtastoma

Background: We evaluated the potential of bioluminescence imaging (BLI) for early tumor detection, demonstrating occult sites of disseminated disease and assessing disease progression in a murine model of neuroblastoma. Methods: Neuroblastoma cells engineered to express the enzyme firefly luciferase were used to establish localized tumors and disseminated disease in SCID mice. Bioluminescent signal intensity was measured at serial time points, and compared with traditional methods of evaluating tumor growth. Results: Bioluminescence imaging detected subcutaneous and retroperitoneal tumors weeks before they were palpable or appreciable by ultrasound. Bioluminescent signal intensity at both sites then paralleled tumor growth. After intravenous administration of tumor cells, BLI revealed disseminated disease in the liver, lungs, and bone marrow, again weeks before any gross disease was present. The presence of tumor within these sites at early time points was confirmed by reverse transcriptase-polymerase chain reaction. Finally, BLI permitted a real-time, noninvasive, quantitative method for following response to therapy in a model of minimal residual disease. Conclusion: Bioluminescence imaging detects tumor much earlier than traditional methods. In addition, it can detect, quantify, and follow micrometastasis in real-time during disease progression. This methodology is extremely valuable for studying tumor tissue tropism, mechanisms of metastasis, and response to therapy in murine tumor models. (c) 2007 Elsevier Inc. All rights reserved.