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

Ann Surg. 2015 Feb;261(2):395-404. doi: 10.1097/SLA.0000000000000602.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopropionitrile
  • Animals
  • Aorta, Abdominal / diagnostic imaging*
  • Aorta, Abdominal / metabolism
  • Aorta, Abdominal / pathology
  • Aortic Aneurysm, Abdominal / chemically induced
  • Aortic Aneurysm, Abdominal / diagnostic imaging*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Rupture / chemically induced
  • Aortic Rupture / diagnostic imaging*
  • Aortic Rupture / metabolism
  • Aortic Rupture / pathology
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Fluorodeoxyglucose F18*
  • Male
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Aminopropionitrile