Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis.
OBJECTIVE
To assess the expression of the cytokine-inducible endothelial leukocyte adhesion molecule E-selectin during the evolution of urate crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique.


METHODS
Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E-selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy.


RESULTS
MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E-selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student's t-test).


CONCLUSIONS
E-selectin is expressed by synovial endothelium during the evolution of urate crystal-induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E-selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.
Chapman
P T
PT
Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Jamar
F
F
Harrison
A A
AA
Binns
R M
RM
Peters
A M
AM
Haskard
D O
DO
D000818:Animals; D001168:Arthritis / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D015815:Cell Adhesion Molecules / Q000032:analysis; D019040:E-Selectin; D004727:Endothelium / Q000737:chemistry; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D011877:Radionuclide Imaging; D013552:Swine; D013583:Synovial Membrane / Q000737:chemistry; D014527:Uric Acid
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007205:Indium Radioisotopes; D014527:Uric Acid