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Imaging the Parasympathetic Cardiac Innervation with PET

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Autonomic Innervation of the Heart

Abstract

Parasympathetic tone plays a critical role as modulator of the cardiac sympathetic nervous system the healthy and diseased heart and has a major impact upon the occurrence of arrhythmias and sudden death. Decreased parasympathetic tone is an important prognostic factor in heart failure. Abnormalities of both systems, sympathetic and parasympathetic, have been shown to be either global or regional. This represents a major rationale for the use of imaging techniques to measure autonomic nervous system function, particularly as the other clinical tools such as heart rate variability are of limited value.

Positron emission tomography (PET) imaging with short half-life positron-labeled specific ligands allows this evaluation. However, PET measures the labeled ligand concentration, but the quantification of the receptor density and affinity requires mathematical modeling to simulate the kinetics of the labeled molecule in the tissue, with the use of compartmental analysis and complex protocols. These protocols include injection not only of the tracer but also of pharmacological doses of the cold ligand for co-injection or displacement experiments.

PET imaging with [11C]-methyl-quinuclidin-3-yl benzilate has been validated as an accurate tool to measure muscarinic receptor density and affinity constants in patients with heart failure, including postinfarction patients. A novel (α4β2) nicotinic acetylcholine receptor PET ligand, 2-[18F]-F-A-85380, was also used in patients for evaluation of left ventricular and arterial wall nicotinic receptors.

Although limited today to research centers, PET imaging of the cardiac parasympathetic innervation provides new insight into pathophysiological processes and can be used for the evaluation of new drugs. In the future, it could emerge as a reference for validation of more simple tools and of easier imaging protocols and for early diagnosis, monitoring of treatment, and determination of individual outcome.

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Abbreviations

ACh:

Acetylcholine

DCM:

Dilated cardiomyopathy

DMSO:

Dimethyl sulfoxide

ECG:

Electrocardiogram

FAP:

Familial amyloid polyneuropathy

FDG:

Fluorodeoxyglucose

HPLC:

High-performance liquid chromatography

mAChR:

Muscarinic acetylcholine receptor

MR:

See mAChR

MSA:

Multiple system atrophy

nAChR:

Nicotinic acetylcholine receptor

NMS:

N-Methylscopolamine

PET:

Positron emission tomography

QNB:

3-Quinuclidinyl benzilate (or quinuclidin-3-yl benzilate)

ROI:

Region of interest

SD:

Standard deviation

SE:

Standard error

SPECT:

Single-photon emission computed tomography

SPET:

See SPECT

SUV:

Standardized uptake value

TBP:

Tributyl phosphate

TFA:

Trifluoroacetic acid

TTR:

Transthyretin (gene)

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Authors and Affiliations

  1. Department of Nuclear Medicine, Inserm U1148, Laboratory for Vascular Translational Science, Bichat University Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Diderot-Paris 7, 46 rue Henri Huchard, Paris, 75018, France

    Dominique Le Guludec

  2. 4 allée du Moulin à Bareau, Briis Sous Forges, 91640, France

    Jacques Delforge

  3. CEA, I2BM, Service Hospitalier Frédéric Joliot, 4 place du Général Leclerc, Orsay, 91406, France

    Frédéric Dollé

Authors
  1. Dominique Le Guludec
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  2. Jacques Delforge
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  3. Frédéric Dollé
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Correspondence to Dominique Le Guludec .

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Editors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Riemer H.J.A. Slart

  2. Thorax center Cardiology, University Medical Center Groningen, Groningen, The Netherlands

    René A. Tio

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Philip H. Elsinga

  4. Nuklearmedizinische Klinik, Klinikum Rechts der Isar Technische Universität München, München, Germany

    Markus Schwaiger

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Le Guludec, D., Delforge, J., Dollé, F. (2015). Imaging the Parasympathetic Cardiac Innervation with PET. In: Slart, R., Tio, R., Elsinga, P., Schwaiger, M. (eds) Autonomic Innervation of the Heart. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45074-1_6

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