The evaluation of anti-angiogenic effects of Endostar on rabbit VX2 portal vein tumor thrombus using perfusion MSCT

BACKGROUND There were many treatments for hepatocellular carcinoma with portal vein tumor thrombus (PVTT), in which targeted anti-angiogenic drug therapy is becoming a popular research topic. However, an objective and non-invasive method that can evaluate the treatment effects is still lacking. METHODS Eighteen New Zealand white rabbits implanted with VX2 tumor thrombus in portal vein were randomly assigned into 3 groups: Endostar, saline, or control, six in each group. Multi-slice CT (MSCT) perfusion scanning was performed to measure the differences in blood flow (TBF), tissue blood volume (TBV), and capillary permeability time the surface (PS) before and after Endostar treatment, between Endostar and saline treatment. Two weeks after treatment, both Endostar and saline groups underwent CT perfusion scan. The rabbits then were sacrificed by air embolism, and specimens of tumor thrombosis were collected. Immunohistochemistry assay was also performed to compare the expression of vascular endothelial growth factor (VEGF) in PVTT after Endostar, saline and placebo treatment. RESULTS In Endostar group, PVTT CT perfusion parameters (TBF, TBV, PS) significantly decreased after the treatment (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were significantly lower in Endostar group than in Saline group (p <0.05). VEGF is mainly expressed in cytoplasma. After Endostar treatment, the expression of VEGF in PVTT was markedly reduced. There was also significant difference on post-treatment VEGF protein expression measured by Immunohistochemistry assay between Endostar group and control group (p <0.05). Post-treatment PVTT CT perfusion parameters (TBF, TBV, PS) were positively correlated with VEGF protein expression in all 3 groups (rs > 0, p <0.05). CONCLUSIONS Multi-slice CT perfusion imaging can evaluate the anti-angiogenic effects of Endostar for the VX2 tumor thrombus in portal vein, and provide quantitative functional information.