Application of small animal in vivo imaging system Spectrum-CT in establishing orthotopic model of human lung cancer in nude mice / 肿瘤研究与临床

ABSTRACT

Objective:To provide more valuable experimental animal models for lung cancer research, three kinds of orthotopic human lung neoplasms models in nude mice were established and their biological characteristics were monitored and compared by using small animal in vivo imaging system Spectrum-CT.Methods:Human lung cancer A549 cell line stably expressing luciferase (A549-Luc) was constructed and three kinds of orthotopic human lung cancer models in nude mice (6 mice/each group) were established by means of intrapleural injection, tail vein injection and tracheal perfusion with A549-Luc cells, respectively. Additionally, bioluminescence imaging was performed on model mice by using Spectrum-CT imaging system to monitor the growth of tumor tissues and the intensity of fluorescence signal once a week for 4 consecutive weeks. Finally, the lung tissues of model mice were dissected for in vitro bioluminescence imaging and pathological analysis.Results:The results of bioluminescence imaging analysis revealed that the transplanted tumor tissues of all three groups continued to growth. At the 4th week after cell inoculation, the fluorescence signal intensity of the mice in the intrapleural injection group [(2.78±0.18)×10 6 P/s] was significantly higher than that in the tracheal perfusion group [(1.45±0.20)×10 6 P/s] and the tail vein injection group [(1.35±0.14)×10 6 P/s] (F = 62.53, P < 0.01). The 3D in vivo imaging analysis showed that the tumor tissues had different growth states in three orthotopic lung cancer models. The intrapleural injection model had a single tumor focus at the inoculation site of the right lung lobe. The tumor tissues of the tracheal perfusion model showed an uncertain multi-point growth pattern in the left and right lung lobes. In the tail vein injection model, the tumor foci were relatively evenly distributed in the left and right lobes. Conclusions:Compared with the tracheal perfusion model and the tail vein injection model, the intrapleural injection orthotopic lung cancer model shows stronger tumorigenic ability and has advantage in the study of the active location of transplanted tumor. Combined with Spectrum-CT in vivo imaging system, real-time localization and quantitative analysis of the tumor growth can be performed at an early stage of transplantation, which can provide a valuable experimental method for the pathogenesis and pharmaceutical research of lung cancer.