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

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.

• Authors: Hui Tan, Jun Zhou, Xiangdong Yang, Mieradilijiang Abudupataer, Xiao Li, Yan Hu, Jie Xiao, Hongcheng Shi, Dengfeng Cheng
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 3504 (06 14 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28615707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Apolipoproteins E
• Radiopharmaceuticals
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Bevacizumab
• Atorvastatin

Topics

• Angiogenesis Inhibitors (administration & dosage)
• Animals
• Apolipoproteins E (genetics)
• Atorvastatin (administration & dosage)
• Bevacizumab (administration & dosage)
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Neovascularization, Pathologic (diagnostic imaging, drug therapy, etiology)
• Plaque, Atherosclerotic (complications)
• Radiopharmaceuticals (administration & dosage)
• Single Photon Emission Computed Tomography Computed Tomography (methods)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, immunology)