Abstract
Background: We aimed to develop a contrast agent suitable for targeting to E-selectin expressed on activated vascular endothelium in an in vivo model of inflammation and detection by magnetic resonance (MR) imaging.
Methods: Anti-murine E-selectin F(ab')2 monoclonal antibody (mAb) (MES-1) was conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO). Flow cytometry, PERL staining for iron, and MR imaging were performed using CHO cells expressing mouse E-selectin (CHO-E) 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, with serial imaging being performed using an Oxford/Varian 9.4T MR imaging system with a custom receive-only coil. Tissue sections were stained to define the distribution of E-selectin expression and the localisation of the MES-1-USPIO conjugate.
Results: The MES-1-USPIO was shown to bind to CHO-E in vitro. Following injection of MES-1-USPIO in vivo, distinct changes in the R2 relaxation rate (1/T2) characteristics could be detected in inflamed ears compared to controls. Histological analysis confirmed the vascular endothelial distribution of the MES-1-USPIO.
Conclusions: E-selectin expression in vivo can be selectively and directly imaged non-invasively with magnetic resonance. This molecular imaging tool has the potential to be useful for the diagnosis and monitoring of early or occult inflammation, and may provide an attractive alternative to established clinical investigations such as the use of radiolabelled leukocytes. In addition, such an agent may have value in the investigation of some solid tumours and metastases, either by targeting tumour-associated neovasculature or tumour cells expressing E-selectin.
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Reynolds, P., Larkman, D., Haskard, D. et al. 304 Detection of Vascular Expression of E-Selectin in Vivo by Mr Imaging. Pediatr Res 58, 407 (2005). https://doi.org/10.1203/00006450-200508000-00333
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DOI: https://doi.org/10.1203/00006450-200508000-00333