Research Article

Molecular Imaging and Biology

, Volume 13, Issue 3, pp 462-470

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Andreas R. BaudyAffiliated withResearch Center for Genetic Medicine, Children’s National Medical CenterDepartment of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences
  • , Arpana SaliAffiliated withResearch Center for Genetic Medicine, Children’s National Medical Center
  • , Sarah JordanAffiliated withResearch Center for Genetic Medicine, Children’s National Medical Center
  • , Akanchha KesariAffiliated withResearch Center for Genetic Medicine, Children’s National Medical Center
  • , Helen K. JohnstonAffiliated withResearch Center for Genetic Medicine, Children’s National Medical CenterDepartment of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences
  • , Eric P. HoffmanAffiliated withResearch Center for Genetic Medicine, Children’s National Medical CenterDepartment of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences
  • , Kanneboyina NagarajuAffiliated withResearch Center for Genetic Medicine, Children’s National Medical CenterDepartment of Integrative Systems Biology, George Washington University School of Medicine and Health Sciences Email author 

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.

Key words

Live optical imaging Duchenne muscular dystrophy mdx Cathepsin B Muscle inflammation