Abstract 529: Increased 18F-FDG Uptake in the Aortic Wall of β-aminopropionitrile Exposed Rats May be Predictive of AAA Rupture

Abstract

Objectives: Ruptured abdominal aortic aneurysm (AAA) is associated with a uniformly high mortality rate, and a noninvasive method is necessary to detect vascular wall inflammation that may assist in predicting AAA rupture. The ability of 18F-FDG positron emission tomography to identify increased inflammation in the porcine pancreatic elastase (PPE) perfusion model in Sprague-Dawley rats exposed to β-aminopropionitrile (BAPN) to stimulate AAA rupture was evaluated. Methods: BAPN (300mg/kg subcutaneous) was administered daily starting 3d prior to infrarenal abdominal aortic exposure to PPE and daily until AAA harvest or rupture (BAPN, n=10). Control rats only underwent PPE exposure (n=8). Aortic diameter was evaluated at 3, 7, and 14d post PPE exposure utilizing ultrasound (US, 12MHz). Both groups were imaged with 18F-FDG microPET. AAA maximum to mean muscle 18F-FDG uptake ratios (AMR) were determined. AAA rupture sites were identified at post rupture harvest. Matrix metalloproteinase (MMP) 2 and 9 zymogramatic activities, in terms of integrated optical density (IOD), were assessed at 7d (control n=3, BAPN n=4) and 14d post PPE exposure (control n=3, rupture n=3). Results: Mean 7d aortic diameter increases of 251 ± 29.4% and 340 ± 56.0% (p=0.20) were observed in control and rupture groups, respectively. Four BAPN exposed rats ruptured within 24h after 18F-FDG microPET. Considering the entire AAA, mean AMRs for control and ruptured groups were not significantly different at 15.3 ± 1.6 and 15.5 ± 1.9, respectively. However, considering the 18F-FDG uptake at known rupture sites, the mean AMR for ruptured AAAs was significantly greater than that of control AAAs (AMR 13.2 ± 1.1 vs. 8.4 ± 1.3, p=0.02). IOD values of 8373 ± 827 and 4655 ± 1851 (p=0.14) were observed for MMP9 activity in 14d control and ruptured AAA tissue, representing an 80% increase in ruptured AAA tissue. IOD values of 4760 ± 647 and 1190 ± 87 (p=0.03) were observed for MMP2 activity in 14d control and ruptured AAA tissue, respectively, representing a 75% decrease in ruptured AAA tissue. No differences in MMP2 or 9 activities for control and BAPN exposed rats were appreciated at 7d post PPE exposure. Conclusions: Increased MMP9 activity in ruptured rat AAA tissue parallels what has been observed in ruptured human AAA tissue. Decreased MMP2 activity in ruptured AAA tissue may represent decreased smooth muscle cell presence. Increased 18F-FDG uptake by rat AAA walls, in regions of known rupture, suggests that FDG-PET may be used to predict AAA rupture.