Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis

Circ Res. 2015 Aug 28;117(6):502-512. doi: 10.1161/CIRCRESAHA.115.306364. Epub 2015 Jul 21.


Rationale: The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis.

Objective: This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes.

Methods and results: We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte-mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504±263 versus 194±77 fluorescence intensities in hearts; P=0.002).

Conclusions: Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention.

Keywords: dexamethasone; granzyme; immunology; molecular imaging; myocarditis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • Enzyme Activation / physiology
  • Fluorescent Dyes / analysis
  • Granzymes / analysis
  • Granzymes / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocarditis / enzymology*
  • Myocarditis / immunology*
  • Myocarditis / pathology


  • Fluorescent Dyes
  • Granzymes
  • Gzmb protein, mouse