RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease

Mol Imaging Biol. 2012 Jun;14(3):315-24. doi: 10.1007/s11307-011-0495-1.

Abstract

Purpose: Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease.

Procedures: Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging.

Results: RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions.

Conclusions: RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aortic Diseases / pathology
  • Carotid Arteries / anatomy & histology
  • Carotid Arteries / pathology
  • Carotid Artery Diseases / pathology*
  • Cattle
  • Cells, Cultured
  • Diagnostic Techniques, Cardiovascular
  • Disease Models, Animal
  • Endothelial Cells / pathology
  • Ferritins* / chemistry
  • Ferritins* / metabolism
  • Humans
  • Immunohistochemistry
  • Inflammation / pathology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Nanoparticles* / chemistry
  • Neovascularization, Pathologic / pathology*
  • Oligopeptides* / chemistry
  • Oligopeptides* / metabolism
  • Protein Binding
  • Spectrometry, Fluorescence / methods
  • Spectroscopy, Near-Infrared / methods
  • Tomography

Substances

  • Oligopeptides
  • arginyl-glycyl-aspartic acid
  • Ferritins