99mTc-labeled bevacizumab for detecting atherosclerotic plaque linked to plaque neovascularization and monitoring antiangiogenic effects of atorvastatin treatment in ApoE\u2212/\u2212 mice

Hui Tan,Xiangdong Yang,Mieradilijiang Abudupataer,Yan Hu,Jun Zhou,Jie Xiao,Hongcheng Shi,Dengfeng Cheng,Xiao Li

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.

Highlights

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
A variety of factors have been found to contribute to the process of angiogenesis, vascular endothelial growth factor-A (VEGF-A) is recognized as the predominant proangiogenic factor[9, 10]
Golestani et al.[23] used 89Zr- bevacizumab ex vivo imaging to evaluate excised carotid artery atherosclerotic plaque, and the results showed both that 89Zr-bevacizumab uptake was obviously correlated with VEGF immunohistochemical staining scores, and that it is possible to detect VEGF using 89Zr-bevacizumab PET

Summary

Introduction

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. In this study, we designed and prepared 99mTc-labeled bevacizumab as a probe for plaque neovascularization imaging in an ApoE−/− atherosclerotic mice model.

Results

Conclusion