title: 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis.
abstract: Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM).
  
  
  METHODS
  Autoimmune myocarditis was induced by immunizing Lewis rats twice with porcine cardiac myosin and Freund complete adjuvant. Control animals were treated with adjuvant alone. Dual-tracer autoradiography was performed to assess14C-methionine uptake and to compare the distributions of14C-methionine versus18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac11C-methionine PET was performed to evaluate the feasibility of in vivo imaging.18F-FDG PET was also conducted to compare the in vivo uptake of11C-methionine and18F-FDG.
  
  
  RESULTS
  Multiple focal cardiac inflammatory lesions were histologically identified in myosin-immunized rats, whereas no cardiac lesions were observed in the controls. Autoradiographic images clearly showed a high-density accumulation of14C-methionine in inflammatory lesions of EAM rats, whereas no significant uptake was observed in the control animals.14C-methionine uptake was significantly higher in inflammatory lesions than in remote noninflammatory areas and control rat hearts. The distribution of14C-methionine correlated well with that of18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for18F-FDG than for14C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional11C-methionine uptake (percentage injected dose per cubic centimeter) observed in EAM rats was significantly higher than the values obtained for control animals (0.64 ± 0.09 vs. 0.28 ± 0.02, respectively; P < 0.001). A good positive correlation between11C-methionine and18F-FDG uptake was found.
  
  
  CONCLUSIONS
  In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.|Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Maya
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.|Else-Kröner-Forschungskolleg, Interdisciplinary Center for Clinical Research, University of Würzburg,Würzburg, Germany.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Werner
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.|Department of Pharmacology, University of Würzburg, Würzburg, Germany; and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schütz
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wakabayashi
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.|Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.|Department of Pharmacology, University of Würzburg, Würzburg, Germany; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Zechmeister
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.|Interdisciplinary Bank of Biomaterials and Data Würzburg (IBDW), University of Würzburg, Würzburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Jahns
authors.affiliation: Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.|Department of Pharmacology, University of Würzburg, Würzburg, Germany; and.
authors.forename: Valérie
authors.initials: V
authors.lastname: Jahns
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Würzburg, Germany thiguchi@me.com.|Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D001692:Biological Transport; D002250:Carbon Radioisotopes; D004195:Disease Models, Animal; D005260:Female; D008715:Methionine / Q000737:chemistry / Q000378:metabolism; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D051381:Rats
chemical_list: D002250:Carbon Radioisotopes; D008715:Methionine
keywords: 11C-methionine; 18F-FDG; myocarditis; positron emission tomography; rat