Effect of angiogenesis inhibitor Avastin treatment on distribution of blood flow andaccumulation of boron compounds in murine tumors

Abstract

Previous studies have demonstrated that angiogenesis inhibitor treatment can affect tumors vessels. Here, we studied the effects of angiogenesis inhibitor Avastin on tumor blood perfusion and boron-10 compound accumulation in murine tumor model. The human squamous cell carcinoma (SAS) cells and human malignant glioblastoma cells (U87-MG) were used. In cultured SAS and U87-MG cells, the distribution of boron compound BPA (p-boronophenylalanine) was investigated by immunofluorescence staining using antibody of BPA. The boron-10 concentrations in tumor were measured by prompt gamma-ray spectrometry (PGA). Tumor blood flow assay was also performed. The fluorescence intensity of BPA in cultured cells was increased with the increasing concentration of 10B. Two days after Avastin treatment, the concentration of 10B in tumor was increased than that in non-treatment tumor. The enhancing micro-distribution of BPA and Hoechst33342 perfusion was also observed on 2 days after Avastin administration in tumor tissues. In this study, we demonstrated that Avastin treatment enhances tumor blood perfusion and BPA accumulation in tumors. These results suggest that the combination of angiogenesis inhibitor treatment with boron compound administration may be useful to improve boron compound distribution in tumor, then to enhance the efficacy of BNCT, which is due to the changes in the extracellular microenvironment, including in tumor vessels.