Integrin-targeted molecular imaging of experimental abdominal aortic aneurysms by 18F-labeled Arg-Gly-Asp positron-emission tomography

Abstract

Background-Both inflammation and neoangiogenesis contribute to abdominal aortic aneurysm (AAA) disease. Arg-Gly-Asp-based molecular imaging has been shown to detect the integrin α β3. We studied a clinical dimeric 18F-labeled v| Arg-Gly-Asp positron-emission tomography (PET) agent (18F-FPPRGD2) for molecular imaging of experimental AAAs. Methods and Results-Murine AAAs were induced in Apo-E-deficient mice by angiotensin II infusion, with monitoring of aortic diameter on ultrasound. AAA (n=10) and saline-infused control mice (n=7) were injected intravenously with 18F-FPPRGD2, as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of 18F-FPPRGD2 was quantified by percentage-injected dose per gram and target-to-background ratio. Focal increased PET signal was found in AAA lesions, but not in normal control aortae, confirmed by quantitative analysis (median percentage-injected dose per gram [interquartile range], 2.05 [1.05-2.85] versus 0.63 [0.43-0.83], P=0.003; median target-to-background ratio [interquartile range], 2.72 [2.31-3.49] versus 1.44 [1.10-1.52], P=0.0008). Ex vivo autoradiography demonstrated high uptake of 18F-FPPRGD 2 into the AAA wall, with immunohistochemistry showing substantial cluster of differentiation (CD)-11b+ macrophages and CD-31 + neovessels. Target-to-background ratio of AAAs on PET did not correlate with AAA diameter (r=-0.29, P=0.41) but did strongly correlate with both mural macrophage density (r=0.79, P=0.007) and neovessel counts (r=0.87, P=0.001) on immunohistochemistry. Conclusions-PET imaging of experimental AAAs using 18F-FPPRGD2 detects biologically active disease, correlating to the degree of vascular inflammation and neoangiogenesis. This may provide a clinically translatable molecular imaging approach to characterize AAA biology to predict risk beyond size alone. © 2013 American Heart Association, Inc.