Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2990263 | Journal of Vascular Surgery | 2012 | 9 Pages |
ObjectiveAbdominal aortic aneurysm (AAA) is a frequent form of atherothrombotic disease, whose natural history is to enlarge and rupture. Indicators other than AAA diameter would be useful for preventive surgery decision-making, including positron-emission tomography (PET) methods permitting visualization of aortic wall leukocyte activation relevant to prognostic AAA evaluation. In this study, we compare three PET tracers of activated leukocytes, 18F-fluoro-deoxy-glucose (FDG), 18F-fluoro-methyl-choline (FCH), and 18F-DPA714 (a peripheral benzodiazepine receptor antagonist) for in vivo PET quantification of aortic wall inflammation in rat experimental AAAs, in correlation with histopathological studies of lesions.MethodsAAAs were induced by orthotopic implantation of decellularized guinea pig abdominal aorta in 46 Lewis rats. FDG-PET (n = 20), FCH-PET (n = 8), or both (n = 12) were performed 2 weeks to 4 months after the graft, 1 hour after tracer injection (30 MBq). Six rats (one of which had FDG-PET) underwent 18F-DPA714-PET. Rats were sacrificed after imaging; AAAs and normal thoracic aortas were cut into axial sections for quantitative autoradiography and histologic studies, including ED1 (macrophages) and CD8 T lymphocyte immunostaining. Ex vivo staining of AAAs and thoracic aortas with 18F-DPA714 and unlabeled competitors was performed.ResultsAAAs developed in 35 out of 46 cases. FCH uptake in AAAs was lower than that of FDG in all cases on imaging, with lower AAA-to-background maximal standardized uptake value (SUVmax) ratios (1.78 ± 0.40 vs 2.71 ± 0.54; P < .01 for SUVmax ratios), and lower AAA-to-normal aorta activity ratios on autoradiography (3.52 ± 1.26 vs 8.55 ± 4.23; P < .005). FDG AAA-to-background SUVmax ratios correlated with the intensity of CD8 + ED1 staining (r = .76; P < .03). FCH AAA-to-background SUVmax ratios correlated with the intensity of ED1 staining (r = .80; P < .03). 18F-DPA714 uptake was similar in AAAs and in normal aortas, both in vivo and ex vivo.ConclusionsIn rat experimental AAA, characterized by an important aortic wall leukocytes activity, FDG-PET showed higher sensitivity than FCH-PET and 18F-DPA714-PET to detect activated leukocytes. This enhances potential interest of this tracer for prognostic evaluation of AAA in patients.
Clinical RelevanceThe decision for preventive surgery of abdominal aortic aneurysm (AAA) is based on clinical signs and AAA diameter. However, AAA progression is not linear; growth acceleration usually precedes rupture. Therefore, other indicators of lesion development would be useful for surgical decision-making. Adventitial inflammation has been linked to AAA enlargement. Therefore, positron-emission tomography (PET) imaging quantifying activated leukocytes in aortic wall could be useful for prognostic evaluation of AAAs. In this experimental study comparing three main PET tracers of activated leukocytes, we show that 18F-fluoro-deoxy-glucose has the highest sensitivity of detection and appears the most promising for clinical use in this setting.