Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress

Federico Moccetti, Craig C. Weinkauf, Brian P. Davidson, J. Todd Belcik, Edmund R. Marinelli, Evan C Unger, Jonathan R. Lindner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO). Histology was performed on carotid endarterectomy samples from patients undergoing surgery for unstable atherosclerosis to assess target expression in humans. In DKO mice, CEUS signal for all four targeted MBs was significantly higher than that for control MBs, and was three to sevenfold higher than in wild-type mice, with the highest signal achieved for VCAM-1 and VWF. All molecular targets were present on the patient plaque surface but expression was greatest for VCAM-1 and VWF. We conclude that ultrasound contrast agents bearing small peptide ligands feasible for human use can be targeted against endothelial cell adhesion molecules for inflammatory cells and platelets for imaging advanced atherosclerotic disease.

Original languageEnglish (US)
JournalUltrasound in Medicine and Biology
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

arteriosclerosis
Molecular Imaging
Vascular Cell Adhesion Molecule-1
von Willebrand Factor
markers
peptides
Ultrasonography
Atherosclerosis
Oxidative Stress
Ligands
Inflammation
mice
Contrast Media
Peptides
ligands
Microbubbles
Carotid Endarterectomy
Cell Adhesion Molecules
Atherosclerotic Plaques
endothelium

Keywords

  • Atherosclerosis
  • Contrast-enhanced ultrasound
  • Microbubbles
  • Molecular Imaging

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Biophysics
  • Acoustics and Ultrasonics

Cite this

Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress. / Moccetti, Federico; Weinkauf, Craig C.; Davidson, Brian P.; Belcik, J. Todd; Marinelli, Edmund R.; Unger, Evan C; Lindner, Jonathan R.

In: Ultrasound in Medicine and Biology, 01.01.2018.

Research output: Contribution to journalArticle

Moccetti, Federico ; Weinkauf, Craig C. ; Davidson, Brian P. ; Belcik, J. Todd ; Marinelli, Edmund R. ; Unger, Evan C ; Lindner, Jonathan R. / Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress. In: Ultrasound in Medicine and Biology. 2018.
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