Synergistic Effect of Anti-Angiogenic and Radiation Therapy: Quantitative Evaluation with Dynamic Contrast Enhanced MR Imaging.

Abstract

PURPOSE: We assessed the effects of anti-angiogenic therapy (AAT) on radiation therapy (RT), evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR) images. METHODS: Thirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2), AAT (n = 2), RT (n = 5), and combined therapy (AART, n = 4). DCE-MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test. RESULTS: Tumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016) and the maximum enhancement ratio (P<0.016) of AART group were higher than those of RT group. CONCLUSIONS: AART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group.