NONINVASIVE IMAGING OF E-SELECTIN EXPRESSION BY ACTIVATED ENDOTHELIUMIN URATE CRYSTAL-INDUCED ARTHRITIS

Objective. To assess the expression of the cytokine-inducible endothel ial leukocyte adhesion molecule E-selectin during the evolution of ura te crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique. Methods. Monosodium mate (MSU) crystals and saline alone were injected respectively into the ri ght (inflamed) and left (control) knees of 3 young pigs. Four hours la ter, In-111-labeled 1.2B6 F(ab')(2) (anti-E-selectin MAb) and I-125-la beled MOPC 21 F(ab')(2) (control MAb) were injected intravenously. Upt ake of 1.2B6 in inflamed and control joints was assessed by scintigrap hy 7 and 24 hours after intraarticular injection of MSU crystals. Immu nohistochemistry studies and radioactivity counting of tissues were pe rformed postmortem to confirm the observations from scintigraphy. Resu lts. MAb 1.2B6 F(ab')(2) scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 2 4 hours postinjection, particularly over the joint space. These in viv o images were consistent with E-selectin expression in the inflamed ti ssue detected by immunohistochemistry and with radioactivity counts po stmortem. The synovial localization ratio (inflamed:control synovium c ounts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb comp ared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student 's t-test). Conclusion. E-selectin is expressed by synovial endotheliu m during the evolution of urate crystal-induced arthritis and can be d etected noninvasively using a radiolabeled MAb. This E-selectin imagin g technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumati c diseases.