Abstract
27
Objectives Vascular adhesion protein-1 (VAP-1) plays a key role in recruiting leukocytes into sites of inflammation. Using a phage display approach, we have recently discovered that sialic acid-binding Ig-like lectin 9 (Siglec-9) is a leukocyte ligand for VAP-1 and [18F]FDR-Siglec-9 specifically detects VAP-1 in vasculature at sites of inflammation. This study investigated the uptake of a novel [18F]FDR-Siglec-9 tracer in inflamed atherosclerotic plaques in mice.
Methods Atherosclerotic LDLR-/-ApoB100/100 (n=12) and C57BL control mice (n=9) were intravenously injected with 20 MBq of [18F]FDR-Siglec-9. Radioactivity concentration was measured in the aorta, and other tissues by gamma counter. In addition, the aorta was studied in more detailed by autoradiography, histology and immunohistochemistry. The specificity of tracer binding was studied with in vitro competitive assay with human atherosclerotic lesions.
Results The aorta uptake of [18F]FDR-Siglec-9 was significantly higher in the LDLR-/-ApoB100/100 mice (0.80±0.36 %IA/g) compared to control mice (0.44±0.15 %IA/g, P=0.01). The autoradiography demonstrated significantly higher radioactivity concentration in atherosclerotic plaques compared to healthy vessel wall or adjacent adventitia. Plaque-to-wall ratio was 1.9±0.3 (p=0.003) and plaque-to-adventitia ratio was 2.4±0.6 (p=0.004). Competition with excess of unlabeled peptide decreased tracer binding by 8-folds in human atherosclerotic lesions. The expression of VAP-1 in human and murine plaques was confirmed by positive anti-VAP-1 staining.
Conclusions VAP-1 targeting [18F]FDG-Siglec-9 peptide binds to the murine and human atherosclerotic plaques and it might be promising and novel PET tracers for detection of plaque inflammation.