Molecular Imaging of Vulnerable Plaques in Rabbits Using Contrast-Enhanced Ultrasound Targeting to Vascular Endothelial Growth Factor Receptor-2

Molecular Imaging of Vulnerable Plaques in Rabbits Using Contrast-Enhanced Ultrasound Targeting to Vascular Endothelial Growth Factor Receptor-2
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使用针对血管内皮生长因子受体 2 的对比增强超声对家兔易损斑块进行分子成像

DOI:
10.1002/jcu.20759
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发表时间:
2011-02-01
影响因子:
0.9
通讯作者:
Gao, Yun-Hua
Gao, Yun-Hua
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Hong;Wang, Xiang;Gao, Yun-Hua

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目的:新生血管增多已被确认为动脉粥样硬化斑块易损性的一个特征,并可通过微泡超声造影剂(UCA)进行追踪。在易损斑块模型中,我们研究了靶向UCA的血管内皮生长因子受体2(VEGFR-2)的滞留与VEGFR-2表达的关系。方法:通过链霉亲和素将生物素标记的微泡与生物素标记的VEGFR-2抗体偶联,制备靶向VEGFR-2的微泡。通过将重组P53腺病毒运送到腹主动脉因高胆固醇饮食和球囊内皮损伤而获得的动脉粥样硬化斑块,造成了脆弱性。12周后,测量超声造影前后图像的平均视频强度。结果:靶向UCA在斑块中的存留率高于非靶向UCA(144+/-18dBvs107+/-9dB;Z=-3.984,p=0.000)。VEGFR-2的表达与靶向UCA的视频强度呈正相关(r(2)=0.78,p=0.001),而与非靶向UCA的视频强度无关(r(2)=0.17,p>=0.05)。这些结果验证了靶向UCA用于兔易损腹主动脉斑块的超声成像的有效性。2010年Wiley期刊,Inc.临床超声杂志39:83-90,2011;在线出版于Wiley在线图书馆(wileyonlinelibrary.com)。DOI:10.1002/jcu.20759
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 plagues 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 39:83-90, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jcu.20759