Abstract
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 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA) specimens. Five CEA specimens were coincubated with 89Zr-bevacizumab and aspecific 111In-labeled IgG to determine the specificity of bevacizumab accumulation. In 11 CEA specimens, 89Zr-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 89Zr-bevacizumab compared to 111In-IgG uptake was demonstrated by gamma counting. The mean %Inc/ghot 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 (ρ = .74, p < .001). It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. 89Zr-bevacizumab accumulation in plaques is specific and correlates with immunohistochemistry scores.
Highlights
Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture
We investigated whether 89Zr-bevacizumab vascular endothelial growth factor (VEGF) imaging is feasible to detect VEGF in human carotid endarterectomy (CEA) specimens
In all CEA specimens, clear 89Zr-bevacizumab uptake within the arterial wall was seen (Figure 1). 89Zr-bevacizumab uptake in all plaques was heterogeneously distributed
Summary
Intraplaque angiogenesis is associated with the occurrence of atherosclerotic plaque rupture. Cardiovascular molecular imaging can be used for the detection of rupture-prone plaques. We determined the feasibility of 89Zr-bevacizumab imaging for the detection of VEGF in carotid endarterectomy (CEA) specimens. It is feasible to detect VEGF tissue concentration within CEA specimens using 89Zr-bevacizumab PET. Intraplaque release of vascular endothelial growth factor (VEGF) is known to be an important process linked to plaque vulnerability.[2] Both VEGF and local hypoxia result predominantly in chemotactic processes within plaques. This process leads to the formation of immature blood vessels and subsequent intraplaque hemorrhage, thereby causing plaque instability. Clinical detection of intraplaque concentration of VEGF may be used for the assessment of plaque vulnerability
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