Objective:

To develop and validate a targeted ultrasonographic (US) imaging agent with microbubbles (MBs) that binds to vascular endothelial growth factor receptor 2 (VEGFR2) in a murine model for tumor angiogenesis.

Methods:

Targeted US imaging agent was prepared by bridged avidin biotin through binding anti-VEGFR2 antibody to the shell of perfluorocarbonfilled MBs. The binding specificities of targeted MB (MBv) and with nonlabeled MB (MBc) were tested with VEGFR2-positive cells (human umbilical vein endothelial cells

HUVECs). In vivo imaging signals of contrast-enhanced US by using anti-VEGFR2-targeted MBv and MBc were quantified

in 10 mice bearing GL261 cells.

Results:

Attachment of HUVECs was significantly higher for MBv (mean MBs per cell 9.50.5) than MBc (mean MBs per cell 1.50.3). The imaging signal in the murine tumor angiogenesis model was significantly higher for MBv than for MBc.

Conclusion:

Targeted contrast-enhanced US directed at VEGFR2 improves in vivo visualization of tumor angiogenesis and boundary identification in a murine model of orthotopic gliomas.