Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2.

Abstract

PURPOSE Increased neovascularization has been identified as a feature of atherosclerotic plaque vulnerability and can be traced by microbubble ultrasound contrast agents (UCA). We investigated the relationship between retention of a vascular endothelial growth factor receptor 2 (VEGFR-2) targeted UCA and VEGFR-2 expression in a vulnerable plaque model in rabbits. METHODS Microbubbles targeting to VEGFR-2 were prepared by conjugation of biotinylated microbubbles with biotinylated VEGFR-2 antibody via streptavidin. Vulnerability was created by delivering recombinant p53 adenovirus to atherosclerotic plaques obtained in abdominal aorta by a high cholesterol diet and balloon endothelial injury. Twelve week later, the average video intensity of pre- and postcontrast ultrasound images was measured. VEGFR-2 expression and vascular density were quantified by immunohistochemical staining. RESULTS Retention of targeted UCA in plaques was higher than that of nontargeted UCA (144 ± 18 dB versus 107 ± 9 dB; Z= -3.984, p = 0.000). VEGFR-2 expression was correlated with video intensity of targeted (r(2) = 0.78, p = 0.001), but not of nontargeted, UCA (r(2) = 0.17, p ≥ 0.05). CONCLUSIONS The magnitude of the sonographic signal from retained VEGFR-2 targeted UCA correlates with VEGFR-2 expression. These results validate the use of targeted UCA for sonographic imaging of vulnerable abdominal artery plaques in rabbits.

DOI: 10.1002/jcu.20759
0501001502011201220132014201520162017
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@article{Liu2011MolecularIO, title={Molecular imaging of vulnerable plaques in rabbits using contrast-enhanced ultrasound targeting to vascular endothelial growth factor receptor-2.}, author={Hong Liu and Xiang Wang and Kai-Bing Tan and Ping Liu and Zhong-Xiong Zhuo and Zheng Liu and Xing Hua and Qin-Qiang Zhuo and Hong-mei Xia and Yun-hua Gao}, journal={Journal of clinical ultrasound : JCU}, year={2011}, volume={39 2}, pages={83-90} }