In SCID 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

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Abstract

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 125I-R-125224 to SCID-HuRAg mice (0.4 mg/kg). The in vitro binding of 125I-R-125224 to isolated human synovial cells was investigated.

Results

After intravenous administration of 125I-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 125I-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.

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