title: Integrin-targeted imaging of inflammation in vascular remodeling.
abstract: OBJECTIVE
  Inflammation plays a key role in the development of vascular diseases. Monocytes and macrophages express α(v)β(3) integrin. We used an α(v) integrin-specific tracer, (99m)Tc-NC100692, to investigate integrin-targeted imaging for detection vessel wall inflammation.
  
  
  RESULTS
  The binding of a fluorescent homologue of NC100692 to α(v)β(3) on human monocytes and macrophages was shown by flow cytometry. Vessel wall inflammation and remodeling was induced in murine carotid arteries through adventitial exposure to CaCl(2). NC100692 micro single photon computed tomography/CT imaging was performed after 2 and 4 weeks and showed significantly higher uptake of the tracer in CaCl(2)-exposed left carotids compared with sham-operated contralateral arteries. Histological analysis at 4 weeks demonstrated significant remodeling of left carotid arteries and considerable macrophage infiltration, which was confirmed by real-time polymerase chain reaction. There was no significant difference in normalized α(v), β(3), or β(5) mRNA expression between right and left carotid arteries. Finally, NC100692 uptake strongly correlated with macrophage marker expression in carotid arteries.
  
  
  CONCLUSIONS
  NC100692 imaging can detect vessel wall inflammation in vivo. If further validated, α(v)-targeted imaging may provide a noninvasive approach for identifying patients who are at high risk for vascular events and tracking the effect of antiinflammatory treatments.
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Razavian
authors.forename: Ravi
authors.initials: R
authors.lastname: Marfatia
authors.forename: Heloise
authors.initials: H
authors.lastname: Mongue-Din
authors.forename: Sina
authors.initials: S
authors.lastname: Tavakoli
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Sinusas
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.forename: Mehran M
authors.initials: MM
authors.lastname: Sadeghi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002122:Calcium Chloride / Q000009:adverse effects; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010456:Peptides, Cyclic; D012333:RNA, Messenger / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D001057:Apolipoproteins E; D005456:Fluorescent Dyes; D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; C521545:NC100692; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D002122:Calcium Chloride