Longitudinal 18F-FDG PET imaging in a rat model of autoimmune myocarditis

Rudolf A. Werner, Hiroshi Wakabayashi, Jochen Bauer, Claudia Schütz, Christina Zechmeister, Nobuyuki Hayakawa, Mehrbod S. Javadi, Constantin Lapa, Roland Jahns, Süleyman Ergün, Valerie Jahns, Takahiro Higuchi

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Abstract

Aims Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-18F-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. Methods and results Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund's adjuvant. Time course of disease was assessed by longitudinal 18F-FDG PET imaging. A correlative analysis between in-and ex vivo 18F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal 18F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo 18F-FDG PET signalling (R2 = 0.92) as well as with ex vivo 18F-FDG autoradiography (R2 = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at 18F-FDG decrease). Conclusion 18F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.

Original languageEnglish
Pages (from-to)467-474
Number of pages8
JournalEuropean Heart Journal Cardiovascular Imaging
Volume20
Issue number4
DOIs
Publication statusPublished - Apr 1 2019
Externally publishedYes

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Keywords

  • F-FDG
  • inflammation
  • myocarditis
  • personalized treatment
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Werner, R. A., Wakabayashi, H., Bauer, J., Schütz, C., Zechmeister, C., Hayakawa, N., Javadi, M. S., Lapa, C., Jahns, R., Ergün, S., Jahns, V., & Higuchi, T. (2019). Longitudinal 18F-FDG PET imaging in a rat model of autoimmune myocarditis. European Heart Journal Cardiovascular Imaging, 20(4), 467-474. https://doi.org/10.1093/ehjci/jey119