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  • Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI.

Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI.

Arteriosclerosis, thrombosis, and vascular biology (2014-06-07)
Xiang Li, Wolfgang Bauer, Ina Israel, Michael C Kreissl, Johannes Weirather, Dominik Richter, Elisabeth Bauer, Volker Herold, Peter Jakob, Andreas Buck, Stefan Frantz, Samuel Samnick
ABSTRACT

Nuclear imaging of active plaques still remains challenging. Advanced atherosclerotic plaques have a strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques, but not on the endothelium overlying inactive fibrous plaques. We proposed a new approach for noninvasive in vivo characterization of P-selectin on active plaques based on (68)Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity. (68)Ga-Fucoidan was tested for its potential to discriminate vulnerable plaques on apolipoprotein E-deficient mice receiving a high cholesterol diet by positron emission tomography and in correlation with 17.6T MRI. Furthermore, (68)Ga-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active plaques using autoradiography. The cellular uptake rate was increased ≈2-fold by lipopolysaccharide induction. Interestingly, on autoradiography, more intensive tracer accumulation at active plaques with thin fibrous caps and high-density foam cells were observed in comparison with a weaker focal uptake in inactive fibrous plaque segments (R=1.7±0.3; P<0.05) and fatty streaks (R=2.4±0.4; P<0.01). Strong uptake of radiotracer colocalized with increased P-selectin expression and high-density macrophage. Focal vascular uptake (mean of target to background ratio=5.1±0.8) of (68)Ga-Fucoidan was detected in all apolipoprotein E-deficient mice. Anatomic structures of plaque were confirmed by 17.6T MRI. The autoradiography showed a good agreement of (68)Ga-Fucoidan uptake with positron emission tomography. Our data suggest that (68)Ga-Fucoidan represents a versatile imaging biomarker for P-selectin with the potential to specifically detect P-selectin expression using positron emission tomography and to discriminate vulnerable plaques in vivo.

MATERIALS
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Fucoidan from Macrocystis pyrifera, ≥85%
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Fucoidan from Fucus vesiculosus, Crude
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Fucoidan from Undaria pinnatifida, ≥95%
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Sigma-Aldrich
Fucoidan from Fucus vesiculosus, ≥95%
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