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Imaging Vascular Endothelial Activation: An Approach Using Radiolabeled Monoclonal Antibodies Against the Endothelial Cell Adhesion Molecule E-Selectin

Departments of Medicine and Diagnostic Radiology, Royal Postgraduate Medical School, Hammersmith Hospital, London
Immunology Division, AFRC Babraham Institute, Babraham, Cambridge, United Kingdom

Correspondence: For correspondence and reprints contact: Dr. D.O. Haskard, Dept. of Medicine, R.P.M.S., Hammersmith Hospital, Du Cane Rd., London W12 0NN, U.K.

ABSTRACT

E-selectin is an endothelial cell-specific adhesion molecule for leukocytes expressed on the luminal surface of vascular endothelium during inflammatory responses. Because E-selectin expression is dependent upon ongoing stimulation by cytokines, this molecule offers a potentially useful target for imaging tissues in disease states involving cytokine-mediated endothelial cell activation. Method: To assess the imaging potential of an anti-E-selectin monoclonal antibody (Mab) 1.2B6, the accumulation of intravenously injected ¹¹¹In-labeled Mab 1.2B6 was compared to that of ¹¹¹In-control antibody in a model of arthritis in the pig. Injection of phytohaemagglutinin (PHA) into a knee led to E-selectin expression on vessels in the synovium and draining deep inguinal lymph nodes, as demonstrated by immunohistology. No E-selectin expression was seen in the control knee injected with buffer alone. Animals were given ¹¹¹In-Mab 1.2B6 or ¹¹¹In-control antibody intravenously 3 hr after the intra-articular injection of PHA Radiolabeled antibody uptake was measured by direct counting of tissues 25 hr postmortem. Results: The accumulation of radiolabeledcontrol IgG in synovium and draining deep inguinal lymph nodes of PHA-injected knees was significantly higher than accumulation in tissues injected with buffer alone; however, the comparable ratios in animals receiving radiolabeled Mab 1.2B6 were significantly greater. Scintigraphy performed 24 hr after ¹¹¹In-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. This approach may be useful for investigating activated endothelium in human disease.

Key Words: inflammation • vascular endothelial activation • endothelial cell adhesion • E-selectin

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