Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine

Werner, Rudolf A.; Maya, Yoshifumi; Rischpler, Christoph; Javadi, Mehrbod S.; Fukushima, Kazuhito; Lapa, Constantin; Herrmann, Ken; Higuchi, Takahiro

doi:10.1007/s00259-015-3171-x

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…Heterogenous reduction in myocardial sympathetic innervation in various cardiomyopathies was in line with previous studies [3,5,[7][8][9][10]. Myocardial sympathetic denervation in CAD is observed in the infarct core and the surrounding border zone [3,4,24]. In contrast, denervated myocardium is located in the apex and inferior wall in patients with idiopathic dilated cardiomyopathy [5,7] and in the hypertrophic wall in patients with hypertrophic cardiomyopathy [8], indicating that the heterogenous reduction may not be directly associated with myocardial ischemia in the failing heart.…”

Section: Discussionsupporting

confidence: 87%

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Aikawa

Naya

Obara

et al. 2017

Eur J Nucl Med Mol Imaging

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Section: Discussionsupporting

confidence: 87%

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Aikawa

Naya

Obara

et al. 2017

Eur J Nucl Med Mol Imaging

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“…It has been shown that the 11 C-HED uptake defect areas in both the subacute and chronic phases after transient ischemia were clearly larger than the perfusion defect areas in the midventricular wall. Partial reinnervation could be observed as the uptake of 11 C-HED recovered in the subepicardial portion in the chronic phase (Werner et al 2016). Furthermore, the potential cold mass effect of 11 C-HED (specific activities 0.2-141.9 GBq/µmol) in healthy Wistar rats (ranging 0.2-60.4 µg/kg cold mass) was also investigated, in which a dose-dependent reduction of cardiac 11 C-HED uptake with different specific activities was observed.…”

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confidence: 99%

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

et al. 2020

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The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used 123/131 I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. 11 C-HED and 18 F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed.

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“…Dual-tracer autoradiography was conducted with 14 C-methionine and 18 F-FDG (26). 18 F-FDG (37 MBq) was injected intraperitoneally into conscious rats (n 5 4) after a 14-h fasting period to minimize physiologic cardiac glucose uptake.…”

Section: Ex Vivo Dual-tracer Autoradiographymentioning

confidence: 99%

¹¹C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis

et al. 2016

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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 14 C-methionine uptake and to compare the distributions of 14 C-methionine versus 18 F-FDG. Hematoxylin and eosin staining and anti-CD68 macrophage staining were performed for histologic analysis. Additionally, cardiac 11 C-methionine PET was performed to evaluate the feasibility of in vivo imaging. 18 F-FDG PET was also conducted to compare the in vivo uptake of 11 C-methionine and 18 F-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 14 C-methionine in inflammatory lesions of EAM rats, whereas no significant uptake was observed in the control animals. 14 C-methionine uptake was significantly higher in inflammatory lesions than in remote noninflammatory areas and control rat hearts. The distribution of 14 C-methionine correlated well with that of 18 F-FDG and with macrophage density. The contrast between inflammatory and noninflammatory areas was higher for 18 F-FDG than for 14 C-methionine (3.45 ± 0.68 vs. 2.07 ± 0.21, respectively; P , 0.05). In the PET imaging study, the regional 11 C-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 11 C-methionine and 18 F-FDG uptake was found. Conclusion: In a rat model of autoimmune myocarditis, we demonstrated the colocalization of radiolabeled methionine accumulation with 18 F-FDG uptake in histologically proven inflammatory lesions. These data suggest that 11 C-methionine might represent a promising candidate for the noninvasive detection and monitoring of myocarditis.

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Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine

Cited by 13 publications

References 27 publications

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

¹¹C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis

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Sympathetic nerve damage and restoration after ischemia-reperfusion injury as assessed by 11C-hydroxyephedrine

Cited by 13 publications

References 27 publications

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements

11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis

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¹¹C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis