title: RGD-conjugated human ferritin nanoparticles for imaging vascular inflammation and angiogenesis in experimental carotid and aortic disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305-5233, USA.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.forename: Masaki
authors.initials: M
authors.lastname: Uchida
authors.forename: Monica M
authors.initials: MM
authors.lastname: Dua
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iida
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dalman
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000473:pathology; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000473:pathology; D002340:Carotid Artery Diseases / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D003935:Diagnostic Techniques, Cardiovascular; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014054:Tomography
chemical_list: D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005293:Ferritins