2. Academic Validation
  3. 99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE-/- mice

99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE-/- mice

  • Sci Rep. 2017 Jun 14;7(1):3504. doi: 10.1038/s41598-017-03276-w.
Hui Tan 1 2 3,  Jun Zhou 1 2 3,  Xiangdong Yang 4,  Mieradilijiang Abudupataer 5,  Xiao Li 1 2 3,  Yan Hu 1 2 3,  Jie Xiao 1 2 3,  Hongcheng Shi 6 7 8,  Dengfeng Cheng 9 10 11
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 2 Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China.
  • 3 Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
  • 4 Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 5 Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 6 Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shi.hongcheng@zs-hospital.sh.cn.
  • 7 Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China. shi.hongcheng@zs-hospital.sh.cn.
  • 8 Shanghai Institute of Medical Imaging, Shanghai, 200032, China. shi.hongcheng@zs-hospital.sh.cn.
  • 9 Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.
  • 10 Institute of Nuclear Medicine, Fudan University, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.
  • 11 Shanghai Institute of Medical Imaging, Shanghai, 200032, China. cheng.dengfeng@zs-hospital.sh.cn.
PMID: 28615707 DOI: 10.1038/s41598-017-03276-w
Abstract

Atherosclerotic neovascularization plays a significant role in plaque instability as it provides additional lipids and inflammatory mediators to lesions, and resulting in intraplaque hemorrhage. Vascular endothelial growth factor-A (VEGF-A) is considered the predominant proangiogenic factor in angiogenesis. Bevacizumab, a humanized monoclonal antibody, specifically binds to all VEGF-A isoforms with high affinity. Therefore, in this study, we designed 99mTc-MAG3-bevacizumab as a probe, and then investigated its usefulness as a new imaging agent for the detection of plaque neovessels, while also assessing the therapeutic effect of atorvastatin treatment. The apoE-/- mice treated with atorvastatin were used as the treatment group, and C57BL/6 J mice were selected as the control group. 99mTc-MAG3-bevacizumab uptake was visualized on atherosclerotic lesions by non-invasive in-vivo micro-SPECT/CT and ex-vivo BSGI planar imaging. The value of P/B in each part of the aorta of apoE-/- mice was higher than in the treatment group and the C57BL/6 J mice, which was confirmed by Oil Red O staining, CD31 staining and VEGF immunohistochemistry staining. 99mTc-MAG3-bevacizumab imaging allowed for the non-invasive diagnosis and assessment of plaque neovascularization. Furthermore, this probe may be used as a new molecular imaging agent to assess the antiangiogenic effect of atorvastatin.

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