Utility of 18 F-FDG and 11C-PBR28 microPET for the assessment of rat aortic aneurysm inflammation

Abstract

BACKGROUND: The utility of (18) F-FDG and (11)C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed. METHODS: Utilizing the porcine pancreatic elastase (PPE) perfusion model, abdominal aortas of male Sprague-Dawley rats were infused with active PPE (APPE, AAA; N = 24) or heat-inactivated PPE (IPPE, controls; N = 16). Aortic diameter increases were monitored by ultrasound (US). Three, 7, and 14 days after induction, APPE and IPPE rats were imaged using (18) F-FDG microPET (approximately 37 MBq IV) and compared with (18) F-FDG autoradiography (approximately 185 MBq IV) performed at day 14. A subset of APPE (N = 5) and IPPE (N = 6) animals were imaged with both (11)C-PBR28 (approximately 19 MBq IV) and subsequent (18) F-FDG (approximately 37 MBq IV) microPET on the same day 14 days post PPE exposure. In addition, autoradiography of the retroperitoneal torso was performed after (11)C-PBR28 (approximately 1,480 MBq IV) or (18) F-FDG (approximately 185 MBq IV) administration at 14 days post PPE exposure. Aortic wall-to-muscle ratios (AMRs) were determined for microPET and autoradiography. CD68 and translocator protein (TSPO) immunohistochemistry (IHC), as well as TSPO gene expression assays, were performed for validation. RESULTS: Mean 3 (p = 0.009), 7 (p < 0.0001) and 14 (p < 0.0001) days aortic diameter increases were significantly greater for APPE AAAs compared to IPPE controls. No significant differences in (18) F-FDG AMR were determined at days 3 and 7 post PPE exposure; however, at day 14, the mean (18) F-FDG AMR was significantly elevated in APPE AAAs compared to IPPE controls on both microPET (p = 0.0002) and autoradiography (p = 0.02). Similarly, mean (11)C-PBR28 AMR was significantly increased at day 14 in APPE AAAs compared to IPPE controls on both microPET (p = 0.04) and autoradiography (p = 0.02). For APPE AAAs, inhomogeneously increased (18) F-FDG and (11)C-PBR28 uptake was noted preferentially at the anterolateral aspect of the AAA. Compared to controls, APPE AAAs demonstrated significantly increased macrophage cell counts by CD68 IHC (p = 0.001) as well as increased TSPO staining (p = 0.004). Mean TSPO gene expression for APPE AAAs was also significantly elevated compared to IPPE controls (p = 0.0002). CONCLUSION: Rat AAA wall inflammation can be visualized using (18) F-FDG and (11)C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of (18) F-FDG and (11)C-PBR28 in the noninvasive assessment of human AAA development.