期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 34, 期 8, 页码 1661-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.114.303485
关键词
atherosclerosis; Ga-68-Fucoidan; P-selectin; PET-imaging; plaque
资金
- Deutsche Forschungsgemeinschaft [SFB688, Z02, TP B04/05]
- Bundesministerium fur Bildung und Forschung [BMBF01, EO1004]
Objective-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 Ga-68-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity. Approach and Results-Ga-68-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, Ga-68-Fucoidan was evaluated on endothelial cells in vitro and ex vivo on active plaques using autoradiography. The cellular uptake rate was increased approximate to 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 Ga-68-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 Ga-68-Fucoidan uptake with positron emission tomography. Conclusions-Our data suggest that Ga-68-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.
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