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

✍ Scribed by Hong Liu; Xiang Wang; Kai-Bing Tan; Ping Liu; Zhong-Xiong Zhuo; Zheng Liu; Xing Hua; Qin-Qiang Zhuo; Hong-Mei Xia; Yun-Hua Gao

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 470 KB
• Volume: 39
• Category: Article
• ISSN: 0091-2751
• DOI: 10.1002/jcu.20759

✦ Synopsis

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. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20759