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

Sci Rep. 2021 Feb 3;11(1):2899. doi: 10.1038/s41598-021-82568-8.

Abstract

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.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Asymptomatic Diseases
  • Benzenesulfonates / chemistry
  • Bevacizumab / chemistry
  • Bevacizumab / pharmacology*
  • Carotid Stenosis / diagnosis*
  • Carotid Stenosis / etiology
  • Carotid Stenosis / pathology
  • Carotid Stenosis / surgery
  • Endarterectomy, Carotid
  • Feasibility Studies
  • Female
  • Fluorescent Dyes / chemistry
  • Humans
  • Indoles / chemistry
  • Male
  • Middle Aged
  • Molecular Imaging / methods
  • Optical Imaging / methods*
  • Plaque, Atherosclerotic / complications*
  • Plaque, Atherosclerotic / pathology
  • Plaque, Atherosclerotic / surgery
  • Severity of Illness Index
  • Vascular Endothelial Growth Factor A / analysis*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Benzenesulfonates
  • Fluorescent Dyes
  • IRDye 800CW
  • Indoles
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab