Objective:

To investigate the feasibility of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast-enhanced ultrasound in monitoring

the efficacy of antiangiogenic therapy in a subcutaneous xenograft tumor model of HCCLM3.

Methods:

Anti-VEGFR2 monoclonal antibody was conjugated onto the surface of lipid microbubbles by the biotinavidin interaction. The vascular effects of therapy were examined in mice carrying HCCLM3 xenografts.

In vivo

molecular contrastenhanced ultrasound imaging with VEGFR2-targeted microbubbles was performed before and 2

7 d after bevacizumab or saline treatment. Intratumoral perfusion areas were quantified by binarizing ultrasound images and the microvessel density was observed by CD31 immunohistochemistry. Perfusion parameters derived from time-intensity curve (TIC) were compared between the bevacizumab group and the control group

and longitudinal comparison of the parameters within the two groups was performed.

Results:

Although tumor volume was not significantly different between the two groups throughout the therapy period

longitudinal analysis of perfusion parameters showed a significant decrease in time to peak (TTP)

mean transit time (MTT) and area under curve(AUC) 7 d after bevacizumab treatment

but no significant changes appeared in the control group. There was a significant difference in area under the wash-in curve (WiAUC) between the two groups on day 7. Immunohistochemistry confirmed the lower microvessel density in the bevacizumab group.

Conclusion:

The efficacy of antiangiogenic therapy could be noninvasively monitored with VEGFR2-targeted ultrasound in a murine model of human liver cancer with a significant decline of multiple perfusion parameters.