title: Integrin-targeted molecular imaging of experimental abdominal aortic aneurysms by (18)F-labeled Arg-Gly-Asp positron-emission tomography.
abstract: BACKGROUND
  Both inflammation and neoangiogenesis contribute to abdominal aortic aneurysm (AAA) disease. Arg-Gly-Asp-based molecular imaging has been shown to detect the integrin αvβ3. We studied a clinical dimeric (18)F-labeled Arg-Gly-Asp positron-emission tomography (PET) agent ((18)F-FPPRGD2) for molecular imaging of experimental AAAs.
  
  
  RESULTS
  Murine AAAs were induced in Apo-E-deficient mice by angiotensin II infusion, with monitoring of aortic diameter on ultrasound. AAA (n=10) and saline-infused control mice (n=7) were injected intravenously with (18)F-FPPRGD2, as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of (18)F-FPPRGD2 was quantified by percentage-injected dose per gram and target-to-
  
  
  BACKGROUND
  =0.003; median target-to-
  
  
  BACKGROUND
  =0.0008). Ex vivo autoradiography demonstrated high uptake of (18)F-FPPRGD2 into the AAA wall, with immunohistochemistry showing substantial cluster of differentiation (CD)-11b(+) macrophages and CD-31(+) neovessels. Target-to-
  
  
  BACKGROUND
  =-0.29, P=0.41) but did strongly correlate with both mural macrophage density (r=0.79, P=0.007) and neovessel counts (r=0.87, P=0.001) on immunohistochemistry.
  
  
  CONCLUSIONS
  PET imaging of experimental AAAs using (18)F-FPPRGD2 detects biologically active disease, correlating to the degree of vascular inflammation and neoangiogenesis. This may provide a clinically translatable molecular imaging approach to characterize AAA biology to predict risk beyond size alone.
authors.affiliation: Division of Cardiovascular Medicine.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kosuge
authors.forename: Edwin
authors.initials: E
authors.lastname: Chang
authors.forename: Michelle L
authors.initials: ML
authors.lastname: James
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dalman
authors.forename: Michael V
authors.initials: MV
authors.lastname: McConnell
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging* / Q000378:metabolism; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009842:Oligopeptides; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid
keywords: aneurysm; arginyl-glycyl-aspartic acid; macrophages; positron-emission tomography