IMAGING VASCULAR ENDOTHELIAL ACTIVATION - AN APPROACH USING RADIOLABELED MONOCLONAL-ANTIBODIES AGAINST THE ENDOTHELIAL-CELL ADHESION MOLECULE E-SELECTIN

E-selectin is an endothelial cell-specific adhesion molecule for leuko cytes expressed on the luminal surface of vascular endothelium during inflammatory responses. Because E-selectin expression is dependent upo n ongoing stimulation by cytokines, this molecule offers a potentially useful target for imaging tissues in disease states involving cytokin e-mediated endothelial cell activation. Method: To assess the imaging potential of an anti-E-selectin monoclonal antibody (Mab) 1.2B6, the a ccumulation of intravenously injected In-111-labeled Mab 1.2B6 was com pared to that of In-111-control antibody in a model of arthritis in th e pig. Injection of phytohaemagglutinin (PHA) into a knee led to E-sel ectin expression on vessels in the synovium and draining deep inguinal lymph nodes, as demonstrated by immunohistology. No E-selectin expres sion was seen in the control knee injected with buffer alone. Animals were given In-111-Mab 1.2B6 In-111-control antibody intravenously 3 hr after the intra-articular lar injection of PHA. Radiolabeled antibody uptake was measured by direct counting of tissues 25 hr postmortem. R esults: The accumulation of radiolabeled control IgG in synovium and d raining deep inguinal lymph nodes of PHA-injected knees was significan tly higher than accumulation in tissues injected with buffer alone; ho wever, the comparable ratios in animals receiving radiolabeled Mab 1.2 B6 were significantly greater. Scintigraphy performed 24 hr after In-1 11-Mab 1.2B6 injection showed obvious localization of activity in the inflamed knee in each of three animals. Conclusion: Radiolabeled anti- E-selectin Mab can be used to image localized inflammatory tissues. Th is approach may be useful for investigating activated endothelium in h uman disease.