Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis

Area of Science:

• Molecular imaging
• Immunopathology
• Cardiology

Background:

• Advancing myocarditis research requires molecular imaging tools to understand immunopathologic mechanisms.
• Cytotoxic CD8+ T lymphocytes play a critical role in myocarditis pathogenesis.

Purpose of the Study:

• To validate a novel molecular imaging tool for in vivo visualization of granzyme B activity.
• To assess granzyme B activity as a biomarker in experimental myocarditis.

Main Methods:

• Synthesis and optimization of a fluorogenic substrate for granzyme B activity.
• Ex vivo and in vivo imaging using fluorescence reflectance imaging and fluorescent molecular tomography.
• Validation with histological examination and computed tomography imaging.
• Assessment of anti-inflammatory intervention effects on granzyme B activity.

Main Results:

• The fluorogenic substrate specifically reported granzyme B activity in mouse hearts.
• In vivo imaging localized granzyme B activity in acute myocarditis.
• Dexamethasone treatment significantly reduced granzyme B activity in vivo (P=0.002).

Conclusions:

• Molecular imaging of granzyme B activity enables visualization of T cell-mediated myocardial injury.
• This approach can monitor therapeutic responses to anti-inflammatory interventions in myocarditis.