Feasibility of Vascular Endothelial Growth Factor Imaging in Human Atherosclerotic Plaque Using Zr-89-Bevacizumab Positron Emission Tomography

Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. Imaging with radiolabeled bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF)-A, can depict VEGF levels corresponding to the angiogenic status in tumors. We determined the feasibility of Zr-89-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA) specimens. Five CEA specimens were coincubated with Zr-89-bevacizumab and aspecific In-111-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, Zr-89-bevacizumab micro-positron emission tomography (PET) was performed following 2 hours of incubation. Specimens were cut in 4 mm wide segments and were stained for VEGF and CD68. In each segment, the mean percent incubation dose per gram of tissue (%Inc/g) and tissue to background ratio were determined. A 10-fold higher accumulation of Zr-89-bevacizumab compared to In-111-IgG uptake was demonstrated by gamma counting. The mean %Inc/g(hot) (spot) was 2.2 +/- 0.9 with a hot spot to background ratio of 3.6 +/- 0.8. There was a significant correlation between the segmental tissue to background uptake ratio and the VEGF score (rho = .74, p <.001). It is feasible to detect VEGF tissue concentration within CEA specimens using Zr-89-bevacizumab PET. Zr-89-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.