In vivo imaging of protease activity in arthritis: A novel approach for monitoring treatment response
Version of Record online: 5 AUG 2004
Copyright © 2004 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 50, Issue 8, pages 2459–2465, August 2004
How to Cite
Wunder, A., Tung, C.-H., Müller-Ladner, U., Weissleder, R. and Mahmood, U. (2004), In vivo imaging of protease activity in arthritis: A novel approach for monitoring treatment response. Arthritis & Rheumatism, 50: 2459–2465. doi: 10.1002/art.20379
- Issue online: 5 AUG 2004
- Version of Record online: 5 AUG 2004
- Manuscript Accepted: 1 APR 2004
- Manuscript Received: 20 NOV 2003
- NIH. Grant Numbers: P50-CA-86355, R24-CA-92782, R01-EB-001872
- German Cancer Research Center
- German Research Society. Grant Number: DFG Mu 1383/3-3
Sensitive noninvasive strategies for monitoring treatment response in rheumatoid arthritis (RA) would be valuable for facilitating appropriate therapy and dosing, evaluating clinical outcome, and developing more effective drugs. Because different proteases are highly up-regulated in RA and contribute significantly to joint destruction, in the present study we investigated whether such enzymes are suitable in vivo imaging biomarkers for early evaluation of treatment response in a murine model of RA.
Using a protease-activated near-infrared fluorescence (NIRF) imaging “smart” probe, we examined the presence and distribution of fluorescence in arthritic joints of mice with collagen-induced arthritis by both noninvasive fluorescence imaging and histology. Proteases that target the Lys–Lys cleavage site, including cathepsin B, activate probe fluorescence. Treatment monitoring data were obtained following methotrexate (MTX) therapy.
Twenty-four hours after intravenous injection of the protease sensor, affected toes and paws of arthritic mice showed significantly higher fluorescence intensity than did toes and paws of healthy mice. Fluorescence from the protease probe and cathepsin B antibody histologic staining were localized in the vast majority of cells in the inflamed synovium. In arthritic animals treated with MTX (35 mg of MTX/kg 48 hours prior to probe injection), a significantly lower fluorescent signal (inflamed paws 50%, inflamed toes 70%) was observed as compared with untreated arthritic animals.
Protease-activated NIRF probes are sensitive means of imaging the presence of target enzymes in arthritic joints and can be used for early monitoring of treatment response to antirheumatic drugs such as MTX.