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Molecular Imaging |
1 From the Department of Neonatal Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W121 0NN, England. Received March 29, 2005; revision requested May 24; revision received August 9; accepted September 7; final version accepted January 4, 2006. Supported by the British Heart Foundation, BBSRC. P.R.R. supported by a Clinical Research Fellow Training Grant from the British Heart Foundation. D.O.H. is in receipt of British Heart Foundation professorial support. A.J.T.G. is a BBSRC Research Development Fellow. N.L.K. supported by a Wellcome Trust Clinical Training Fellowship. A.D.E. supported by the Garfield Weston Foundation. Address correspondence to A.D.E. (e-mail: david.edwards{at}imperial.ac.uk).
Purpose: 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.
Materials and Methods: All animal experiments were approved according to animal welfare and local ethics committee regulations. An antimurine 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-1USPIO. 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-1USPIO conjugate.
Results: MES-1USPIO was shown to bind to CHO cells expressing mouse E-selectin in vitro. After injection of MES-1USPIO 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-1USPIO.
Conclusion: 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.
© RSNA, 2006
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