Feasibility of ex vivo fluorescence imaging of angiogenesis in (non-) culprit human carotid atherosclerotic plaques using bevacizumab-800CW

Vascular endothelial growth factor-A (VEGF-A) is assumed to play a crucial role in the development and rupture of vulnerable plaques in the atherosclerotic process. We used a VEGF-A targeted fluorescent antibody (bevacizumab-IRDye800CW [bevacizumab-800CW]) to image and visualize the distribution of VEGF-A in (non-)culprit carotid plaques ex vivo. Freshly endarterectomized human plaques (n=15) were incubated in bevacizumab-800CW ex vivo. Subsequent NIRF imaging showed a more intense fluorescent signal in the culprit plaques (n=11) than in the non-culprit plaques (n=3). A plaque received from an asymptomatic patient showed pathologic features similar to the culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in 91% of the fluorescent culprit plaques, while no VEGF-A expression was found in the non-culprit plaques (p<0.0001). VEGF-A expression was co-localized with CD34, a marker for angiogenesis (p<0.001). Ex vivo near-infrared fluorescence (NIRF) imaging by incubation with bevacizumab-800CW shows promise for visualizing VEGF-A overexpression in culprit atherosclerotic plaques in vivo.

Automated summary

VEGF-A is believed to be involved in the development and rupture of vulnerable plaques in the atherosclerotic process. Using a VEGF-A targeted fluorescent antibody, researchers were able to visualize the distribution of VEGF-A in carotid plaques ex vivo and found more intense fluorescent signals in the culprit plaques compared to non-culprit plaques. Cross-correlation with VEGF-A immunohistochemistry showed co-localization of VEGF-A over-expression in most culprit plaques, suggesting potential for visualizing VEGF-A overexpression in atherosclerotic plaques in vivo.