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

Abstract

BackgroundThe utility of 18 F-FDG and 11C-PBR28 to identify aortic wall inflammation associated with abdominal aortic aneurysm (AAA) development was assessed.MethodsUtilizing 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 11C-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 11C-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.ResultsMean 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 11C-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 11C-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).ConclusionRat AAA wall inflammation can be visualized using 18 F-FDG and 11C-PBR28 microPET revealing regional differences of radiotracer uptake on microPET and autoradiography. These results support further investigation of 18 F-FDG and 11C-PBR28 in the noninvasive assessment of human AAA development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0020-z) contains supplementary material, which is available to authorized users.

Positron Emission Tomography Imaging of Macrophages in Atherosclerosis with 18F-GE-180, a Radiotracer for Translocator Protein (TSPO)

“…High TSPO radioligand uptake to vessel wall has been observed in the same model as in the current study [ 10 , 11 ] and in a rat model of aortic aneurysm [ 26 ]. However, similar vessel wall uptake of TSPO radioligands was not reported in another rat or mouse models [ 23 , 24 ], nor in the previous studies with 11 C-( R )-PK11195 in patients [ 13 , 22 ]. The reason for this might be differences in the TSPO expression or differences between the studied radioligands.…”

“…Novel TSPO-targeting tracers have been studied in preclinical settings to overcome this problem. For example, 18 F-FEDAA1106 has been evaluated in the imaging of the carotid artery cuff model in mice [ 23 ] and 11 C-PBR28 in a rat model of aortic aneurysm [ 24 ]. Both of these studies showed noticeable tracer uptake in lesion areas.…”

In vivo imaging of inflammation and oxidative stress in a nonhuman primate model of cardiac sympathetic neurodegeneration

“… 19 Imaging with TSPO ligands has been used to assess cardiovascular pathologies in humans and in rodent models. 16 , 20 , 21 [ 61 Cu]Diacetyl- bis ( N (4))-methylthiosemicarbazone (ATSM) allows visualization of oxidative stress via bioreductive trapping of the radioactive copper. 22 , 23 PET with ATSM detected oxidative stress in vivo in the striatum of PD patients; 24 this tracer has also been applied to myocardial ischemia in vivo in humans 25 and ex vivo in rodents.…”

[18F]FEPPA Pet Imaging for Monitoring CD68 Positive Microglia/Macrophage Neuroinflammation in Nonhuman Primates

“…The correlation between TSPO PET and CD68-ir is not unique to this study, as English et al (2014) showed that increased uptake of [ 11 C]PBR28 corresponded with a higher CD68 rating in a rat model of aortic aneurysm (50). Hannestad et al (2012) reported that baboons treated systemically with E. coli lipopolysaccharide presented an increase in [ 11 C]PBR28 uptake that positively correlated with serum cytokines IL-1β and IL-6 levels.…”