Abstract
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Objectives Advanced atherosclerotic plaques have strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques, but weak on endothelium overlying inactive fibrous plaques. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. We proposed a new approach for non-invasive PET imaging of P-selectin on vulnerable plaques based on Gallium-68 labelled Fucoidan.
Methods Lipopolysaccharide-induced murine endothelial cells were used to evaluate the ability of 68Ga-Fucoidan to detect P-selectin in vitro. Autoradiography, micro-PET and 17.6T-MRI were performed on ApoE-/- mice with severe atherosclerotic plaques to evaluate the potential of 68Ga-Fucoidan for detecting endothelial P-selectin on vulnerable plaques in vivo.
Results 68Ga-Fucoidan accumulates higher in LPS induced cells. Tracer accumulation in the area of activated plaques with thin fibrous cap and high-density foam cell from each ApoE-/- mouse was higher than the uptake in inactivated fibrous plaque segments (R=1.73±0.3, P <0.05) and endothelial segments without plaques (R=2.35±0.4, P <0.01). Heavy P-selectin expression and high-density macrophage co-localized with increased uptake of tracer. On evaluation of micro-PET scans, localized focal vascular uptakes of 68Ga-Fucoidan were detected in all ApoE-/- mice. The TBRmean was 6.0 ± 1.3. The specific accumulation of radiotracer in atherosclerotic plaques, which were confirmed by 17.6 T MRI noninvasively; the autoradiography of the corresponding aortal sections showed a great agreement of 68Ga-Fucoidan uptake with micro-PET as well.
Conclusions Our data suggest that 68Ga-Fucoidan represents a versatile imaging biomarker for P-selectin with the potential to specifically detect P-selectin expression using PET and to discriminate vulnerable plaques in vivo.