Molecular ultrasound imaging with vascular endothelial growth factor receptor 2-targeted microbubbles in a mouse liver cancer model

TANG Yang; KONG Wentao; ZHANG Xiaolong; WANG Wenping

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Molecular ultrasound imaging with vascular endothelial growth factor receptor 2-targeted microbubbles in a mouse liver cancer model

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- Molecular ultrasound imaging with vascular endothelial growth factor receptor 2-targeted microbubbles in a mouse liver cancer model
- Vol. 25, Issue 4, Pages: 317-321(2016)
- 作者机构：
  
  1. 复旦大学附属中山医院超声科,上海,200032
  2. 南京大学医学院附属鼓楼医院超声科,南京,210008
  3. 上海市影像医学研究所,上海,200032
- 作者简介：
- 基金信息：
- DOI：
  CLC：
- Online First：11 January 2017，
  
  Published：2016
- 稿件说明：
移动端阅览
汤阳,孔文韬,张小龙,等. 靶向血管内皮生长因子受体2微泡造影剂评价肿瘤血管生成的实验研究[J]. 肿瘤影像学, 2016, 25(4): 317-321
DOI：

汤阳,孔文韬,张小龙,等. 靶向血管内皮生长因子受体2微泡造影剂评价肿瘤血管生成的实验研究[J]. 肿瘤影像学, 2016, 25(4): 317-321 DOI：

摘要

目的：

探讨靶向血管内皮生长因子受体2 (vascular endothelial growth factor receptor 2，VEGFR2)微泡造影剂用于肿瘤血管生成的超声分子成像。

方法：

用生物素-亲和素桥接法制备靶向VEGFR2超声微泡，免疫荧光法检测微泡与抗体的结合。建立裸鼠HepG2肝癌皮下种植瘤模型，随机分成靶向组(

=5)和非靶向组(

=5)，经尾静脉团注相同剂量靶向微泡或非靶向微泡，录像并绘制时间-强度曲线(time-intensity curve，TIC)；注入造影剂5 min后利用高声压爆破技术清除肿瘤内部微泡，比较爆破前后两组造影图像灰阶强度的下降，估计靶向微泡在体内与靶点的结合能力。

结果：

靶向造影剂和非靶向造影剂均表现为裸鼠皮下瘤的显著增强，但TIC显示两组间曲线下面积差异有统计学意义[(3 940.4200.9)dBs

. (2 796.8452.3) dBs，

=0.001

]

；微泡爆破后靶向组灰阶强度降低显著大于非靶向组[(7.612.20) dB

.(3.741.40) dB，

=0.010

]

。

结论：

靶向VEGFR2微泡造影剂在体内能显著增强肿瘤血管成像，可作为监测肿瘤血管生成的较可靠分子影像学探针。

Abstract

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

=5; non-targeted group

=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

. (2 796.8452.3) dBs

=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

. (3.741.40) dB

=0.010

]

Conclusion:

Molecular ultrasound imaging with VEGFR2-targeted microbubbles is noninvasive

feasible and reproducible to assess tumor angiogenesis.

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Related Author

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Related Institution

Department of Ultrasound, Nanjing Drum Tower Hospital, Nanjing University

Department of Ultrasound, Nanjing Drum Tower Hospital, Nanjing University Medical School

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