Targeting P-Selectin by Gallium-68–Labeled Fucoidan Positron Emission Tomography for Noninvasive Characterization of Vulnerable PlaquesSignificance
Correlation With In Vivo 17.6T MRI
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 68Ga-Fucoidan, which is a polysaccharidic ligand of P-selectin with a nanomolar affinity.
Approach and Results—68Ga-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, 68Ga-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 68Ga-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 68Ga-Fucoidan uptake with positron emission tomography.
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 positron emission tomography and to discriminate vulnerable plaques in vivo.
- Received February 18, 2014.
- Accepted May 21, 2014.
- © 2014 American Heart Association, Inc.