Dynamic Monitoring Of The Heterogeneity Of Tumor Vascular Of Lung Carcinoma Xenograft Model

Object: To comparison of the effects of different contrast agent in the imaging of ex vivo tumor vascular. To compare the difference of vascular quantitative parameters between two kinds of cells with different VEGF expression levels. To observe the change of tumor vascular with the anti-angiogenesis therapy by bevacizumab.Method: The model of A549 cell xenograft model was constructed, and the tumor model is perfused by different contrast agent (Omnipaque, Barium sulfate suspension and micro-fil). To constructed the model of A549 cell and Calu-6 cell xenograft model. And using western-blot to detect the expression of VEGF in two kinds of cells. Quantitative parameters of tumor vascular in two cell xenograft models at different time points were detected by Micro-CT. To constructed the A549 cell xenograft model, and the experimental group used the intraperitoneal injection of bevacizumab, with normal saline in the control group. The changes of vascular parameters in two groups of xenograft models were evaluated by Micro-CT.Result: The effect of Micro-fil was better than that of barium sulfate suspension and Omnipaque group. The tumor volume, vascular bolume, total number of vascular connections and connections density of high VEGF expression Calu-6 cell model were higher than that of low VEGF expression A549 cell model. However, there was no statistical difference between the two groups in the index, which reflect the vascular geometry complexity such as the surface area and volume ratio, the fractal dimension.The tumor volume, the vascular volume and the total number of connections in Calu-6 cell model increased with time, but the vessel volume fraction and the connections density decreased with time. The vessel volume fraction and the connections density of A549 cell model and increased with time in the early stage, and decreased significantly at nineteenth day. There are significant difference beteen the group of bevacizumab and the control group, in tumor volume and vascular volume, the total number of connections, the connections density. However, compared with the control group, the vessel volume fraction and the connections density in the anti-angiogenesis group were increased slowly,although the results were not statistically significant.Conclusion: Micro-fil is suitable as a contrast agent for ex vivo vascular specimens.There were significant differences in the quantitative parameters of tumor vascular between different VEGF expression tumor models, and VEGF is of great significance in tumor angiogenesis. After anti-VEGF therapy, tumor vascular quantitative parameters were significantly reduced. But the change of vascular quantitative parameters suggest that there are still has other angiogenisis factors in tumor and cause anti-angiogenesis therapy resistance.