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 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.


METHODS
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.


CONCLUSIONS
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.
Keelan
E T
ET
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Harrison
A A
AA
Chapman
P T
PT
Binns
R M
RM
Peters
A M
AM
Haskard
D O
DO
D000818:Animals; D000911:Antibodies, Monoclonal; D001168:Arthritis / Q000139:chemically induced*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D007205:Indium Radioisotopes; D007249:Inflammation / Q000000981:diagnostic imaging*; D010835:Phytohemagglutinins; D011877:Radionuclide Imaging; D013552:Swine
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007205:Indium Radioisotopes; D010835:Phytohemagglutinins