Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture

被引:159
作者
Kang, HW [1 ]
Josephson, L [1 ]
Petrovsky, A [1 ]
Weissleder, R [1 ]
Bogdanov, A [1 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA 02129 USA
关键词
D O I
10.1021/bc0155521
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Covalent conjugates of the cross-linked iron oxide nanoparticles (CLIO) and high-affinity (K-d(app) = 8.5 nM) anti-human E-selectin (CD62E) F(ab')(2) fragments were prepared and tested in vitro to establish feasibility of endothelial proinflammatory marker magnetic resonance (MR) imaging. The conjugates were obtained by using thiol-disulfide exchange reaction between 3-(2-pyridyl)propionyl-CLIO and S-acetylthioacetate-modified F(ab')(2) fragments. The purified CLIO-F(ab')(2) conjugates (average hydrodynamic diameter 40.6 nm) were used in experiments with the live human endothelial umbilical vein cells (HUVEC). Cells treated with IL-1beta expressed E-selectin and showed a 100-200 times higher binding of CLIO particles (83-104 ng iron/million cells) than control cells. The binding resulted in a high superparamagnetism of HUVEC with the transverse water proton relaxation time (T2) decrease to 30-40 ins in cell precipitates. Cells did not bind/internalize CLIO-F(ab')(2) conjugates prepared using a control fragment or nonconjugated iron oxide particles before or after treatment with IL-1beta. MR imaging of cells showed a highly specific T2-weighted signal darkening associated with cells treated with IL-1beta and incubated with anti-E selectin. Demonstration of MR imaging of E-selectin expression justifies further development of MR-targeted agents for monitoring tumor vascular endothelial proliferation, angiogenesis, and atherosclerosis.
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页码:122 / 127
页数:6
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