Non-invasive Optical Imaging of Muscle Pathology in mdx Mice Using Cathepsin Caged Near-Infrared Imaging

Abstract

PURPOSE: To develop a reliable live-animal imaging method for monitoring muscle pathology in mouse models of myopathy. PROCEDURES: A caged near-infrared Cathepsin B (CTSB) substrate, ProSense 680, is evaluated in the dystrophin deficient mdx mice, a genetic homologue of Duchenne muscular dystrophy via optical imaging. RESULTS: We show high levels of infrared signal in dystrophic muscle relative to healthy muscle at 24 h post-injection. Imaging for CTSB presence revealed localization to inflammatory infiltrates and regenerating muscle fibers. A time series myotoxin-induced muscle injury experiment showed that CTSB activity and its mRNA levels peaked at the interface between inflammation and myoblast fusion stage of recovery. Prednisone treatment in mdx mice resulted in decreased CTSB activity and increased grip strength in forelimbs and hindlimbs. CONCLUSIONS: Optical imaging of CTSB activity is an ideal method to sensitively monitor inflammation, regeneration, and response to therapy in myopathic skeletal muscle.