Supplement Article |
OP20. IMAGING ENDOTHELIAL ACTIVATION IN INFLAMMATION
Eric Bywaters Centre for Vascular Inflammation, Hammersmith Hospital, Imperial College, London, UK
Despite the important role that endothelial activation plays during inflammatory responses, molecular changes in endothelium are relatively inaccessible to clinical investigation. E-selectin (CD62E, ELAM-1) is an adhesion molecule expressed on the luminal surface of vascular endothelial cells in inflammation. It serves the function of initiating interactions between the endothelial cell and circulating leucocytes, preceding leukocyte diapedesis into inflamed tissue. E-selectin is not constitutively expressed by endothelial cells but is induced in response to cytokines during many inflammatory conditions, including sepsis, inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. E-selectin represents a potentially useful target for the molecular imaging of endothelial activation, since it is readily accessible to targeting agents. Furthermore, following expression, E-selectin is internalised, and agents conjugated to anti-E-selectin antibodies are taken with E-selectin into the cell, allowing accumulation of targeting agent and increased imaging signal. Monoclonal antibody 1.2B6 is a mouse antibody generated in our laboratory, which primarily reacts with E-selectin but also reacts with P-selectin at about four-fold lower affinity. Using this mAb, we have successfully imaged activated endothelium in vivo using radioscintography. The technique was first evaluated in porcine models of phytohaemaggltinin-induced and MSU crystal-induced arthritis, in which we found that the images of synovitis obtained with 111In-labelled mAb 1.2B6 F(ab')2 were significantly more focal and intense than those obtained with an isotype matched control mAb or 99mTc-labelled leukocytes. We have since shown that 111In-labelled mAb 1.2B6 F(ab')2 could image inflamed joints in patients with RA [1–3] and inflamed bowel in Crohn's Disease and Ulcerative Colitis [4]. More recently we have investigated the possibility of imaging E-selectin by magnetic resonance using anti-E-selectin conjugated ultrasmall superparamagnetic iron oxide nanoparticles.