Integrin-Targeted Molecular Imaging of Experimental Abdominal Aortic Aneurysms by 18F-labeled Arg-Gly-Asp Positron-Emission Tomography

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 (v3). We studied a clinical dimeric F-18-labeled Arg-Gly-Asp positron-emission tomography (PET) agent (F-18-FPPRGD(2)) 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 F-18-FPPRGD(2), as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of F-18-FPPRGD(2) 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 F-18-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 F-18-FPPRGD(2) 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.