Molecular MR Imaging for Visualizing ICAM-1 Expression in the Inflamed Synovium of Collagen-Induced Arthritic Mice

Abstract

Objective: To determine the utility of intercellular adhesion molecule (ICAM)-1 antibody-conjugated gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA-anti-ICAM-1) as a targeted contrast agent for the molecular magnetic resonance imaging (MRI) in collagen-induced arthritis (CIA). Materials and Methods: Three groups of mice were used: non-arthritic normal, CIA mice in both the early inflammatory and chronic destructive phases. The MR images of knee joints were obtained before and after injection of Gd-DTPA-anti-ICAM-1, Gd-DTPA, and Gd-DTPA-Immunoglobulin G (Ig G) and were analyzed quantitatively. The patterns of enhancement on the MR images were compared with the histological and immunohistochemical ICAM-1 staining. Results: The images obtained after injection of Gd-DTPA-anti-ICAM-1 displayed gradually increasing signal enhancement from the moment following injection (mean ± standard deviation [SD]: 424.3 ± 35.2, n = 3) to 24 hours (532 ± 11.3), rather than on pre-enhanced images (293 ± 37.6) in the early inflammatory phase of CIA mice. However, signal enhancement by Gd-DTPA and Gd-DTPA-IgG disappeared after 80 minutes and 24 hours, respectively. In addition, no significant enhancement was seen in the chronic destructive phase of CIA mice, even though they also showed inflammatory changes on T2-weighted MR images. ICAM-1 expression was demonstrated in the endothelium and proliferating synovium of the early inflammatory phase of CIA mice, but not in the chronic destructive phase. Conclusion: Molecular MRI with Gd-DTPA-anti-ICAM-1 displays specific images targeted to ICAM-1 that is expressed in the inflamed synovium of CIA. This novel tool may be useful for the early diagnosis and differentiation of the various stages of rheumatoid arthritis.