Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B of fibronectin

Christian M. Matter, Pia K. Schuler, Patrizia Alessi, Patricia Meier, Romeo Ricci, Dongming Zhang, Cornelia Halin, Patrizia Castellani, Luciano Zardi, Christoph K. Hofer, Matteo Montani, Dario Neri, Thomas F. Lüscher

Research output: Contribution to journalArticle

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 125I-labeled L19 revealed a significant correlation (r=0.89; P-/- 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.

Original languageEnglish
Pages (from-to)1225-1233
Number of pages9
JournalCirculation Research
Volume95
Issue number12
DOIs
Publication statusPublished - Dec 10 2004

Keywords

  • Angiogenesis
  • Apolipoprotein E-null mice
  • Near infrared
  • Vascular targeting

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Matter, C. M., Schuler, P. K., Alessi, P., Meier, P., Ricci, R., Zhang, D., Halin, C., Castellani, P., Zardi, L., Hofer, C. K., Montani, M., Neri, D., & Lüscher, T. F. (2004). Molecular imaging of atherosclerotic plaques using a human antibody against the extra-domain B of fibronectin. Circulation Research, 95(12), 1225-1233. https://doi.org/10.1161/01.RES.0000150373.15149.ff