Rheumatoid arthritis (RA) synovial tissue has been demonstrated to expresses high levels of fibroblast activation protein (FAP) using anti-FAP-antibody 28 H1. In addition, RA patients show elevated levels of IL-22 and IL-22-producing T helper cells that correlate to erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of 111In-28H1 SPECT/CT imaging of FAP-expressing synovium to monitor the therapeutic potential of neutralising IL-22 during experimental arthritis.Materials and methods
Collagen-induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated 3 times per week with anti-IL-22 antibodies (8 mg/kg), while the control group received rat IgG1 isotype control antibodies. To monitor the therapeutic effect after 2 weeks of treatment, SPECT/CT images were acquired 24 hours after injection of 111In-labelled DTPA-conjugated anti-FAP antibody, 28 H1. After image acquisition, mice were euthanized and dissected. Imaging results were compared with the macroscopic arthritis scores, histological damage scores, and radiographic bone damage scores acquired by X-ray.Results
Blocking IL-22 during CIA was a potent approach to prevent arthritis development, reaching a disease incidence of only 50%, versus 100% in the control group. SPECT/CT imaging using indium-labelled anti-FAP antibodies showed that joint uptake of the tracer was significantly reduced in anti-IL-22-treated mice compared to the isotype control group. This was confirmed by the corresponding macroscopic arthritis scores, histological damage scores, and radiographic bone damage scores that were significantly lower in the anti-IL-22-treated group. Besides its sensitivity, the in vivo FAP-based SPECT/CT had the great advantage to visualise sites of inflammation that were overlooked during clinical scoring, like in knee, hip, elbow, and shoulder.Conclusions
These findings demonstrate that IL-22 plays an important role in the development of experimental arthritis, and targeting this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging of the inflamed synovium using the labelled anti-FAP antibody 111In-DTPA-28H1 can be used to specifically monitor response to therapy in an objective and quantitative way, and is potentially more sensitive in disease monitoring compared to the standard method of clinical arthritis scoring by macroscopic inspection.