11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis

Yoshifumi Maya, Rudolf A. Werner, Claudia Schütz, Hiroshi Wakabayashi, Samuel Samnick, Constantin Lapa, Christina Zechmeister, Roland Jahns, Valérie Jahns, Takahiro Higuchi

Research output: Contribution to journalArticle

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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 assess 14C-methionine uptake and to compare the distributions of 14C-methionine versus 18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18F-FDG PET was also conducted to compare the in vivo uptake of 11C-methionine and 18F-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 of 14C-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 of 14C-methionine correlated well with that of 18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18F-FDG than for 14C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional 11C-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 between 11C-methionine and 18F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.

Original languageEnglish
Pages (from-to)1985-1990
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number12
DOIs
Publication statusPublished - Dec 1 2016
Externally publishedYes

Fingerprint

Myocarditis
Methionine
Theoretical Models
Inflammation
Fluorodeoxyglucose F18
Macrophages
Cardiac Myosins
Staining and Labeling
Freund's Adjuvant
Selection Bias
Sudden Cardiac Death
Dilated Cardiomyopathy
Hematoxylin
Myosins
Eosine Yellowish-(YS)
Autoradiography
Young Adult
Swine

Keywords

  • C-methionine
  • F-FDG
  • Myocarditis
  • Positron emission tomography
  • Rat

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis. / Maya, Yoshifumi; Werner, Rudolf A.; Schütz, Claudia; Wakabayashi, Hiroshi; Samnick, Samuel; Lapa, Constantin; Zechmeister, Christina; Jahns, Roland; Jahns, Valérie; Higuchi, Takahiro.

In: Journal of Nuclear Medicine, Vol. 57, No. 12, 01.12.2016, p. 1985-1990.

Research output: Contribution to journalArticle

Maya, Y, Werner, RA, Schütz, C, Wakabayashi, H, Samnick, S, Lapa, C, Zechmeister, C, Jahns, R, Jahns, V & Higuchi, T 2016, '11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis', Journal of Nuclear Medicine, vol. 57, no. 12, pp. 1985-1990. https://doi.org/10.2967/jnumed.116.174045
Maya, Yoshifumi ; Werner, Rudolf A. ; Schütz, Claudia ; Wakabayashi, Hiroshi ; Samnick, Samuel ; Lapa, Constantin ; Zechmeister, Christina ; Jahns, Roland ; Jahns, Valérie ; Higuchi, Takahiro. / 11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 12. pp. 1985-1990.
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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 assess 14C-methionine uptake and to compare the distributions of 14C-methionine versus 18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18F-FDG PET was also conducted to compare the in vivo uptake of 11C-methionine and 18F-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 of 14C-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 of 14C-methionine correlated well with that of 18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18F-FDG than for 14C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional 11C-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 between 11C-methionine and 18F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.",
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T1 - 11C-methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis

AU - Maya, Yoshifumi

AU - Werner, Rudolf A.

AU - Schütz, Claudia

AU - Wakabayashi, Hiroshi

AU - Samnick, Samuel

AU - Lapa, Constantin

AU - Zechmeister, Christina

AU - Jahns, Roland

AU - Jahns, Valérie

AU - Higuchi, Takahiro

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N2 - 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 assess 14C-methionine uptake and to compare the distributions of 14C-methionine versus 18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18F-FDG PET was also conducted to compare the in vivo uptake of 11C-methionine and 18F-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 of 14C-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 of 14C-methionine correlated well with that of 18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18F-FDG than for 14C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional 11C-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 between 11C-methionine and 18F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.

AB - 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 assess 14C-methionine uptake and to compare the distributions of 14C-methionine versus 18F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18F-FDG PET was also conducted to compare the in vivo uptake of 11C-methionine and 18F-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 of 14C-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 of 14C-methionine correlated well with that of 18F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18F-FDG than for 14C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P < 0.05). In the PET imaging study, the regional 11C-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 between 11C-methionine and 18F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.

KW - C-methionine

KW - F-FDG

KW - Myocarditis

KW - Positron emission tomography

KW - Rat

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