Background: 

Prevention of joint destruction and thus patient disability is the most important but hard-to-achieve long-term goal of rheumatoid arthritis (RA) therapy. With a view to improve RA therapy, we evaluated in vivo molecular imaging of matrix metalloproteinase (MMP) activity in an animal model of RA to assess the process of joint destruction and to determine the optimal treatment regimen.

Methods: 

MMP activity was measured weekly for 4 weeks by in vivo imaging of an MMP-activated, fluorescenctly labeled smart probe (MMPsense-680, PerkinElmer) in joints of mice with collagen-induced arthritis (CIA). Treatment groups included saline, dexamethasone (DXA, 0.5 mg/g), etanercept (ETC, 5 mg/g), methotrexate (MTX, 10 mg/g) and ETC + MTX, starting either immediately after arthritis manifestation (early) or one week later (late).

Results: 

Fluorescence imaging showed a steep increase in MMP activity in arthritic mice at the time of clinical manifestation that correlated well with the degree of clinical arthritis severity (r=0.715, p<0.05) and slowly decreased over the following 3 weeks. DXA and early ETC + MTX treatment resulted in significantly lower clinical severity of arthritis compared with saline, whereas the other treatments did not. Correspondingly, MMP activity was found to increase significantly less and to decline more rapidly in the DXA and early ETC + MTX groups compared with saline and all other treatments.

Conclusion: 

In vivo fluorescence imaging of MMP activity in CIA allows effective monitoring of disease activity and treatment response. Early ETC + MTX and DXA therapies are superior to other treatment regimens.