InSCID mice with transplanted joint tissues from rheumatism patients, a model mice of human rheumatoid arthritis, anti-human Fas antibody (R-125224) distributes specifically to human synovium

Purpose. We investigated the tissue distribution of a humanized anti-human Fas monoclonal antibody, R-125224, in SCID mice transplanted with synovial tissues from patients with rheumatoid arthritis (SCID-HuRAg mice). The binding kinetics of R-125224 was also determined, using isolated human synovial cells. Materials and Methods. Tissue distribution was assessed at 1, 24 and 168 h after intravenous administration of I-125-R-125224 to SCID-HuRAg mice (0.4 mg/kg). The in vitro binding of I-125-R-125224 to isolated human synovial cells was investigated. Results. After intravenous administration of I-125-R-125224 to SCID-HuRAg mice, the radioactivity distributed to various tissues at 1 h. Thereafter, the radioactivity in the tissues gradually decreased except for the transplanted synovial tissues, in which the radioactivity increased in a time-dependent manner, and at 168 h, the tissue/plasma concentration ratio was about 1. The in vitro binding affinity of I-125-R-125224 to human synovial cells was high with a dissociation constant of 1.32 +/- 0.62 nM and the binding was inhibited by non-labeled R-125224 in a concentration-dependent manner. Conclusion. R-125224, a candidate compound for treating rheumatoid arthritis, specifically distributed to the pharmacological target site, human synovium transplanted in SCID mice, with high affinity.