Abstract 14044: Dimeric 18F-RGD PET Tracer for αvβ3-Targeted Imaging of Experimental Abdominal Aortic Aneurysm Disease

Abstract

Background: Targeted PET tracers translated to human imaging in cancer and neurology may have utility for cardiovascular diseases. We developed a dimeric RGD ¹⁸F PET tracer (¹⁸F-FPP-RGD2) for enhanced targeting of the integrin αvβ3, which is currently undergoing human oncologic study. Abdominal aortic aneurysm (AAA) disease is a promising application, as neoangiogenesis and inflammation contribute to AAA progression and αvβ3 is expressed highly on both angiogenic endothelial cells and activated macrophages. We evaluated ¹⁸F-FPP-RGD2 PET/CT in a pre-clinical AAA model.

Methods: Murine AAAs were induced in Apo-E deficient mice by angiotensin II infusion, followed by monitoring of aortic diameter on ultrasound (US). AAA (n = 10) and saline-infused control mice (n = 7) were injected intravenously with ¹⁸F-FPP-RGD2 (174 ± 3 μ Ci) and iodine contrast (Fenestra, ART, 0.4 ml). At 60 minutes after injection, mice underwent PET/CT imaging (Inveon, Siemens). Aortic %ID/g and target-to-blood background ratio (TBR) were calculated. Autoradiography and immunohistochemistry (IHC) of aortic tissue sections were also performed.

Results: Increased PET signal was found in AAAs (Fig 1, arrows), but not in normal control aortae, confirmed by quantitative analysis (%ID/g: 1.96 ± 0.29 vs. 0.62 ± 0.11, p = 0.002; TBR: 2.91 ± 0.26 vs. 1.30 ± 0.14, p = 0.0002). Autoradiography demonstrated high uptake of ¹⁸F-FPP-RGD2 in the AAA wall with IHC showing substantial CD-31⁺ neovessels and CD-11b⁺ macrophages (Fig 2). The TBR of AAAs on PET showed positive and strong correlation (Fig 3) with both neovessel counts (r = 0.87, p = 0.001) and macrophage density (r = 0.79, p = 0.007) on IHC, with no significant relationship to aortic diameter by US.

Conclusions: PET/CT using ¹⁸F-FPP-RGD2 detects biologically active murine AAAs, correlating to the degree of vascular neoangiogenesis and inflammation. This may provide a translatable molecular imaging approach to characterize AAA risk beyond diameter alone.