Targeting P-selectin by gallium-68-labeled fucoidan positron emission tomography for noninvasive characterization of vulnerable plaques: correlation with in vivo 17.6T MRI.
Arterioscler Thromb Vasc Biol
; 34(8): 1661-7, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24903095
ABSTRACT
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 (68)Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity. APPROACH ANDRESULTS:
(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.CONCLUSIONS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doenças da Aorta
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Polissacarídeos
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Imageamento por Ressonância Magnética
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Compostos Radiofarmacêuticos
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Células Endoteliais
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Tomografia por Emissão de Pósitrons
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Aterosclerose
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Selenoproteína P
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Imagem Molecular
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Placa Aterosclerótica
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article