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

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 Tc-MAG-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. Tc-MAG-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. Tc-MAG-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.