Objective:

To evaluate the feasibility and reproducibility of molecular ultrasound imaging of tumor angiogenesis with vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles.

Methods:

VEGFR2-targeted microbubbles were accomplished by anti-VEGFR2 monoclonal antibody conjugation to the microbubble surface using biotin-avidin linkage

which was assessed ex vivo using immunofluorescence. Ten mice bearing subcutaneous human liver

tumor were divided into two groups randomly (targeted group

n

=5; non-targeted group

n

=5) and scanned at 2 weeks after implantation with contrast-enhanced ultrasound (CEUS) using either targeted or non-targeted microbubbles. Following CEUS

time-intensity curves were constructed offline and perfusion parameters were calculated. The residual bubble signal was determined 5 min after contrast agent injection with destruction-replenishment analysis.

Results:

Both targeted and non-targeted microbubbles revealed significant enhancement in vivo. A significant difference in area under the curve (AUC) was recorded between targeted group and non-targeted group [(3 940.4200.9) dBs

vs

. (2 796.8452.3) dBs

P

=0.001

]

. After the destruction sequence

there was a significant difference in the decrease of video intensity between targeted group and non-targeted group [(7.612.20) dB

vs

. (3.741.40) dB

P

=0.010

]

.

Conclusion:

Molecular ultrasound imaging with VEGFR2-targeted microbubbles is noninvasive

feasible and reproducible to assess tumor angiogenesis.