Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin - Archive ouverte HAL
Journal Articles Circulation Research Year : 2004

Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin

Christian Matter
  • Function : Author
Pia Schuler
  • Function : Author
Patrizia Alessi
  • Function : Author
Patricia Meier
  • Function : Author
Dongming Zhang
  • Function : Author
Cornelia Halin
  • Function : Author
Patrizia Castellani
  • Function : Author
Luciano Zardi
  • Function : Author
Christoph Hofer
  • Function : Author
Matteo Montani
  • Function : Author
Dario Neri
  • Function : Author
Thomas Lüscher
  • Function : Author

Abstract

Current imaging modalities of human atherosclerosis, such as angiography, ultrasound, and computed tomography, visualize plaque morphology. However, methods that provide insight into plaque biology using molecular tools are still insufficient. The extra-domain B (ED-B) is inserted into the fibronectin molecule by alternative splicing during angiogenesis and tissue remodeling but is virtually undetectable in normal adult tissues. Angiogenesis and tissue repair are also hallmarks of advanced plaques. For imaging atherosclerotic plaques, the human antibody L19 (specific against ED-B) and a negative control antibody were labeled with radioiodine or infrared fluorophores and injected intravenously into atherosclerotic apolipoprotein E–null ( ApoE −/− ) or normal wild-type mice. Aortas isolated 4 hours, 24 hours, and 3 days after injection exhibited a selective and stable uptake of L19 when using radiographic or fluorescent imaging. L19 binding was confined to the plaques as assessed by fat staining. Comparisons between fat staining and autoradiographies 24 hours after 125 I-labeled L19 revealed a significant correlation ( r =0.89; P <0.0001). Minimal antibody uptake was observed in normal vessels from wild-type mice receiving the L19 antibody and in atherosclerotic vessels from ApoE −/− mice receiving the negative control antibody. Immunohistochemical studies revealed increased expression of ED-B not only in murine but also in human plaques, in which it was found predominantly around vasa vasorum and plaque matrix. In summary, we demonstrate selective targeting of atheromas in mice using the human antibody to the ED-B domain of fibronectin. Thus, our findings may set the stage for antibody-based molecular imaging of atherosclerotic plaques in the intact organism.

Dates and versions

hal-03744209 , version 1 (02-08-2022)

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Christian Matter, Pia Schuler, Patrizia Alessi, Patricia Meier, Romeo Ricci, et al.. Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin. Circulation Research, 2004, 95 (12), pp.1225-1233. ⟨10.1161/01.RES.0000150373.15149.ff⟩. ⟨hal-03744209⟩
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