(99m)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 (99m)Tc-MAG(3)-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. (99m)Tc-MAG(3)-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. (99m)Tc-MAG(3)-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.