Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis

Circulation. 2006 Oct 3;114(14):1504-11. doi: 10.1161/CIRCULATIONAHA.106.646380. Epub 2006 Sep 25.


Background: Noninvasive imaging of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) may identify early stages of inflammation in atherosclerosis. We hypothesized that a novel, second-generation VCAM-1-targeted agent with enhanced affinity had sufficient sensitivity to enable real-time detection of VCAM-1 expression in experimental atherosclerosis in vivo, to quantify pharmacotherapy-induced reductions in VCAM-1 expression, and to identify activated cells in human plaques.

Methods and results: In vivo phage display in apolipoprotein E-deficient mice identified a linear peptide affinity ligand, VHPKQHR, homologous to very late antigen-4, a known ligand for VCAM-1. This peptide was developed into a multivalent agent detectable by MRI and optical imaging (denoted VINP-28 for VCAM-1 internalizing nanoparticle 28, with 20 times higher affinity than previously reported for VNP). In vitro, VINP-28 targeted all cell types expressing VCAM-1. In vivo, MRI and optical imaging in apolipoprotein E-deficient mice (n=28) after injection with VINP-28 or saline revealed signal enhancement in the aortic root of mice receiving VINP-28 (P<0.05). VINP-28 colocalized with endothelial cells and other VCAM-1-expressing cells, eg, macrophages, and was spatially distinct compared with untargeted control nanoparticles. Atheromata of atorvastatin-treated mice showed reduced VINP-28 deposition and VCAM-1 expression. VINP-28 enhanced early lesions in juvenile mice and resected human carotid artery plaques.

Conclusions: VINP-28 allows noninvasive imaging of VCAM-1-expressing endothelial cells and macrophages in atherosclerosis and spatial monitoring of anti-VCAM-1 pharmacotherapy in vivo and identifies inflammatory cells in human atheromata. This clinically translatable agent could noninvasively detect inflammation in early, subclinical atherosclerosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoproteins E / deficiency
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology*
  • Diagnostic Imaging / methods
  • Down-Regulation / drug effects
  • Drug Monitoring / methods
  • Gene Expression Regulation / drug effects
  • Inflammation / diagnosis*
  • Ligands
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Knockout
  • Peptides / administration & dosage
  • Peptides / pharmacology
  • Peptides / therapeutic use
  • Vascular Cell Adhesion Molecule-1 / analysis*
  • Vascular Cell Adhesion Molecule-1 / drug effects


  • Apolipoproteins E
  • Ligands
  • Peptides
  • Vascular Cell Adhesion Molecule-1