Multiplex imaging in collagen-induced arthritis models
ProSense, MMPSense , OsteoSense and Quantitative Tomography provide:
- An in vivo map of disease progression and therapeutic response
- Effective and quantifiable detection and measurement of biological changes from the earliest time point
- Disease-related enzyme activity profiles in real time Bone remodeling activity without use of radioisotopes
- Excellent correlation with conventional paw thickness and clinical scoring protocols Provides a greater dynamic range between healthy and arthritic animals than conventional techniques
|Increase in monocyte infiltration/activation (ProSense)||Increase in metalloproteinase activity (MMPSense)|
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.
Data correlates well with conventional techniques and offers a greater dynamic range between arthritic and healthy animals
|Paw thickness and clinical score||0.956|
|Paw thickness and MMPSense pmoles||0.812|
|Paw thickness and ProSense pmoles||0.803|
|Clinical score and MMPSense pmoles||0.860|
|Clinical score and ProSense pmoles||0.863|
|MMPSense pmoles and ProSense pmoles||0.990|
High correlation of OsteoSense (pmoles) with conventional techniques
|Paw thickness and clinical score||0.952|
|Paw thickness and OsteoSense pmoles||0.812|
|Clinical score and OsteoSense pmoles||0.867|