Increased 18f-fdg uptake is predictive of rupture in a novel rat abdominal aortic aneurysm rupture model

Sean J. English, Morand R. Piert, Jose A. Diaz, David Gordon, Abhijit Ghosh, Louis G. D'Alecy, Steven E. Whitesall, Ashish K. Sharma, Elise P. DeRoo, Tessa Watt, G. Su, Peter K. Henke, Jonathan L. Eliason, Gorav Ailawadi, Gilbert R. Upchurch

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Objective: To determine whether 18F-fluorodeoxyglucose (18F-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. 18F-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 18FFDG 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 18F-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 18F-FDG uptake on micro-PET imaging was associated with increased inflammation in the ruptured AAA wall. 18F-FDG PET imaging may be used to monitor inflammatory changes before AAA rupture.

Original languageEnglish
Pages (from-to)395-404
Number of pages10
JournalAnnals of surgery
Volume261
Issue number2
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • AAA rupture
  • FDG-PET
  • IL-6
  • MMP
  • Macrophage

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