Images: Tomographic analysis was performed 24 hours after injection of each fluorescence agent.
Investigation: In this study, monocyte infiltration and activation, metalloproteinase activity and bone remodeling were followed over a 30 day period using the collagen-induced arthritic disease model. DBA/1J mice were injected on Day 1 and again on Day 21 to boost the response. Measurement of paw thickness and a clinical scoring protocol were used to follow disease progress in the conventional manner.
Changes in protease and matrix metalloproteinase activity are known to be involved in the development and maintenance of inflammatory responses in rheumatoid arthritis and skeletal changes also occur.
Detecting enzyme activity: ProSense and MMPSense are activatable fluorescence agents. ProSense is activated predominantly by cathepsin B in vivo (with some ability to be activated by K, L and S, plasmin, plasma kallikrein, uPA and CD10 in vitro) whereas MMPSense is activated by a subset of MMPs, including MMP-2, -3, -9 and -13.
Detecting bone turnover: the fluorescence agent, OsteoSense, targets hydroxyapatite, exposed during times of bone turnover, enabling in vivo detection and monitoring of skeletal changes that occur during either bone growth or bone resorption.
