Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibodies against the endothelial cell adhesion molecule E-selectin

J Nucl Med. 1994 Feb;35(2):276-81.

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 radiolabeled control 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal*
  • Arthritis / chemically induced*
  • Cell Adhesion Molecules / immunology*
  • E-Selectin
  • Endothelium, Vascular / physiology*
  • Indium Radioisotopes
  • Inflammation / diagnostic imaging*
  • Phytohemagglutinins
  • Radionuclide Imaging
  • Swine

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • E-Selectin
  • Indium Radioisotopes
  • Phytohemagglutinins