TY - JOUR
T1 - Longitudinal 18F-FDG PET imaging in a rat model of autoimmune myocarditis
AU - Werner, Rudolf A.
AU - Wakabayashi, Hiroshi
AU - Bauer, Jochen
AU - Schütz, Claudia
AU - Zechmeister, Christina
AU - Hayakawa, Nobuyuki
AU - Javadi, Mehrbod S.
AU - Lapa, Constantin
AU - Jahns, Roland
AU - Ergün, Süleyman
AU - Jahns, Valerie
AU - Higuchi, Takahiro
N1 - Funding Information:
This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and German Research Council (DFG grant HI 1789/3-3). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701983. H.W. has received a JSPS Grant-in-Aid for Research (17K10353).
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - F-FDG
KW - PET
KW - inflammation
KW - myocarditis
KW - personalized treatment
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U2 - 10.1093/ehjci/jey119
DO - 10.1093/ehjci/jey119
M3 - Article
C2 - 30102319
AN - SCOPUS:85063647307
SN - 2047-2404
VL - 20
SP - 467
EP - 474
JO - European heart journal cardiovascular Imaging
JF - European heart journal cardiovascular Imaging
IS - 4
ER -