Detection of vascular expression of E-selectin in vivo with MR imaging.
OBJECTIVE
To develop a contrast agent for targeting E-selectin expressed on activated vascular endothelium and to evaluate detection of the agent with magnetic resonance (MR) imaging in an in vivo mouse model of inflammation.


METHODS
All animal experiments were approved according to animal welfare and local ethics committee regulations. An anti-murine E-selectin F(ab')2 monoclonal antibody, MES-1, was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Flow cytometry, Perl Prussian blue staining for iron, and MR imaging were performed by using Chinese hamster ovary (CHO) cells expressing mouse E-selectin to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO. Serial imaging was performed by using a 9.4-T MR imaging system with a custom receive-only coil. Tissue slices were stained to define distribution of E-selectin expression and localization of the MES-1-USPIO conjugate.


RESULTS
MES-1-USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1-USPIO in vivo, distinct changes in R2 relaxation rate (1/T2) characteristics were detected in inflamed ears when they were compared with control ears. Histologic analysis confirmed the vascular endothelial distribution of MES-1-USPIO.


CONCLUSIONS
E-selectin expression in vivo can be selectively and directly imaged noninvasively with MR. This has the potential to be useful in the study of inflammatory disease.
Reynolds
Peter R
PR
Department of Neonatal Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W121 0NN, England.
Larkman
David J
DJ
Haskard
Dorian O
DO
Hajnal
Joseph V
JV
Kennea
Nigel L
NL
George
Andrew J T
AJ
Edwards
A David
AD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002460:Cell Line; D016009:Chi-Square Distribution; D003287:Contrast Media / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D003911:Dextrans; D019040:E-Selectin / Q000378:metabolism*; D004423:Ear / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005295:Ferrocyanides; D052203:Ferrosoferric Oxide; D005434:Flow Cytometry; D007501:Iron / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D053758:Nanoparticles; D010053:Ovary / Q000166:cytology; D010081:Oxazolone; D010087:Oxides / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D003911:Dextrans; D019040:E-Selectin; D005295:Ferrocyanides; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D010081:Oxazolone; D007501:Iron; C000170:ferric ferrocyanide; D052203:Ferrosoferric Oxide