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[使用琼脂糖流动腔模型对靶向αvβ3整合素的微泡进行血栓的分子成像]

[Molecular imaging of thrombus with microbubbles targeted to alphavbeta3-integrin using an agarose flow chamber model].

作者信息

Hu Guang-quan, Liu Jian, Yang Li, Yan Yi, Wu Jue-fei, Xie Jia-jia, Cai Jing-jing, Ji Li-jing, Bin Jian-ping

机构信息

Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Mar;30(3):478-81.

Abstract

OBJECTIVE

To assess the binding ability of microbubbles targeted to alphavbeta3-integrin (MBp) for thrombus-targeted contrast-enhanced ultrasound.

METHODS

Targeted microbubbles were prepared by conjugating the monoclonal antibody against alphavbeta3-integrin to lipid shell of the microbubble via the avidin-biotin bridges. Equivalent isotype control microbubbles (MB) or targeted ultrasound microbubbles (MBp) were randomly added into the flow chamber. After a 30-min incubation with the thrombus fixed in an agarose flow chamber model, the thrombus was washed with a continuous flow of PBS solution (15 cm/s) for 2, 4, 6, 8 and 10 min, followed by thrombus imaging using contrast-enhanced ultrasound and measurement of the video intensity (VI) values of the images.

RESULTS

The VI of the thrombus in MBp group was reduced by 28%-66%, while that in control MB group was decreased by 87%-94%, and the VI values of the thrombus group were significantly greater in former group at each of the time points (P<0.05).

CONCLUSION

MBP has good targeting ability to the thrombus with resistance to the shear stress after adhesion to the thrombus. In vitro evaluation of the thrombus-binding capability of the targeted microbubble (MBp) by simulating the shear stress in vivo can be helpful for predicting the in vivo effects of ultrasonic molecular imaging using MBp.

摘要

目的

评估靶向αvβ3整合素的微泡(MBp)用于血栓靶向对比增强超声的结合能力。

方法

通过抗生物素蛋白-生物素桥将抗αvβ3整合素单克隆抗体偶联到微泡的脂质壳上,制备靶向微泡。将等量的同型对照微泡(MB)或靶向超声微泡(MBp)随机加入流动腔室。在与固定于琼脂糖流动腔室模型中的血栓孵育30分钟后,用连续流动的PBS溶液(15厘米/秒)冲洗血栓2、4、6、8和10分钟,随后使用对比增强超声对血栓进行成像,并测量图像的视频强度(VI)值。

结果

MBp组血栓的VI降低了28%-66%,而对照MB组降低了87%-94%,在各个时间点,前一组血栓组的VI值均显著高于后一组(P<0.05)。

结论

MBp对血栓具有良好的靶向能力,黏附于血栓后对剪切应力具有抗性。通过模拟体内剪切应力对靶向微泡(MBp)的血栓结合能力进行体外评估,有助于预测使用MBp的超声分子成像的体内效果。

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