title: Increased 18F-FDG uptake is predictive of rupture in a novel rat abdominal aortic aneurysm rupture model.
abstract: OBJECTIVE
  To determine whether F-fluorodeoxyglucose (F-FDG) micro-positron emission tomography (micro-PET) can predict abdominal aortic aneurysm (AAA) rupture.
  
  
  BACKGROUND
  An infrarenal AAA model is needed to study inflammatory mechanisms that drive rupture. F-FDG PET can detect vascular inflammation in animal models and patients.
  
  
  METHODS
  After exposing Sprague-Dawley rats to intra-aortic porcine pancreatic elastase (PPE) (12 U/mL), AAA rupture was induced by daily, subcutaneous, β-aminopropionitrile (BAPN, 300 mg/kg, N = 24) administration. Negative control AAA animals (N = 15) underwent daily saline subcutaneous injection after PPE exposure. BAPN-exposed animals that did not rupture served as positive controls [nonruptured AAA (NRAAA) 14d, N = 9]. Rupture was witnessed using radiotelemetry. Maximum standard uptakes for F-FDG micro-PET studies were determined. Aortic wall PAI-1, uPA, and tPA concentrations were determined by western blot analyses. Interleukin (IL)-1β, IL-6, IL-10, and MIP-2 were determined by Bio-Plex bead array. Neutrophil and macrophage populations per high-power field were quantified. Matrix metalloproteinase (MMP) activities were determined by zymography.
  
  
  RESULTS
  When comparing ruptured AAA (RAAA) to NRAAA 14d animals, increased focal F-FDG uptakes were detected at subsequent sites of rupture (P = 0.03). PAI-1 expression was significantly less in RAAA tissue (P = 0.01), with comparable uPA and decreased tPA levels (P = 0.02). IL-1β (P = 0.04), IL-6 (P = 0.001), IL-10 (P = 0.04), and MIP-2 (P = 0.02) expression, neutrophil (P = 0.02) and macrophage presence (P = 0.002), and MMP9 (P < 0.0001) activity were increased in RAAA tissue.
  
  
  CONCLUSIONS
  With this AAA rupture model, increased prerupture F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture.
authors.affiliation: *Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories †Nuclear Medicine Division ‡Pathology Department, and §Physiology Department, University of Michigan, Ann Arbor, MI; and ¶Vascular and Endovascular Surgery Division, University of Virginia, Charlottesville, VA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: English
authors.forename: Morand R
authors.initials: MR
authors.lastname: Piert
authors.forename: Jose A
authors.initials: JA
authors.lastname: Diaz
authors.forename: David
authors.initials: D
authors.lastname: Gordon
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ghosh
authors.forename: Louis G
authors.initials: LG
authors.lastname: DʼAlecy
authors.forename: Steven E
authors.initials: SE
authors.lastname: Whitesall
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Elise P
authors.initials: EP
authors.lastname: DeRoo
authors.forename: Tessa
authors.initials: T
authors.lastname: Watt
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Eliason
authors.forename: Gorav
authors.initials: G
authors.lastname: Ailawadi
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
mesh_terms: D000629:Aminopropionitrile; D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D001019:Aortic Rupture / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000629:Aminopropionitrile