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Tracers for Sympathetic Cardiac Neurotransmission Imaging

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Autonomic Innervation of the Heart

Abstract

The sympathetic nervous system is the primary extrinsic control of heart rate and contractility and is activated during periods of stress to compensate for increased cardiovascular demand. Signal transduction by the neurotransmitter norepinephrine via postsynaptic β-adrenoceptors and second messenger pathways increases calcium supply in the myocardium, leading to enhanced contractile function. Clinical evidence demonstrates elevated sympathetic tone in cardiovascular disease, resulting in altered expression patterns of multiple proteins involved in sympathetic neuronal transmission. Molecular imaging techniques have been developed targeting these proteins by single-photon emission computed tomography (SPECT) or positron emission tomography (PET). A number of radiotracers have been developed, evaluated, and deployed targeting presynaptic neuronal function (uptake-1 norepinephrine reuptake pathway), postsynaptic α- and β-adrenoceptor density, and second messenger systems (adenylate cyclase/cyclic adenosine monophosphate (cAMP) and phospholipase C/inositol trisphosphate cascades). While the majority of clinical applications to date have utilized analogues of norepinephrine including 123I-metaiodobenzylguanidine ([123I]-MIBG) with SPECT and 11C-meta-hydroxyephedrine ([11C]-mHED) with PET, recent studies have demonstrated added value to multitracer approaches, providing insight not only into neuronal function but also into receptor binding and downstream signaling. In this chapter, the physiology of sympathetic neuronal signaling is discussed with attention to specific targets of current radiotracers in molecular imaging. A summary of the available tracers that have been evaluated in preclinical and clinical settings is provided, with particular attention to those tracers currently utilized in patients.

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Abbreviations

AC:

Adenylate cyclase

AR:

Adrenoceptor

ATP:

Adenosine triphosphate

BNP:

B-type natriuretic peptide

cAMP:

Cyclic adenosine monophosphate

COMT:

Catechol-O-methyltransferase

DA:

Dopamine

DDC:

DOPA-decarboxylase

DOPA:

Dihydrxoyphenylalanine

DβH:

Dopamine-β-hydroxylase

Epi:

Epinephrine

ICD:

Implantable cardioverter-defibrillator

IP3:

Inositol trisphosphate

IPKI:

Isoquinolinesulfonamide protein kinase inhibitor

MAO:

Monoamine oxidase

NE:

Norepinephrine

NYHA:

New York Heart Association

PDE:

Phosphodiesterases

PDE4:

Phosphodiesterase-4

PET:

Positron emission tomography

PKA:

Protein kinase A

PKC:

Protein kinase C

PLC:

Phospholipase C

PMNT:

Phenylethanolamine methyltransferase

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

SPECT:

Single-photon emission computed tomography

TH:

Tyrosine hydroxylase

t-SNARE:

Target-SNARE

Tyr:

Tyrosine

VMAT2:

Vesicular monoamine transporter 2

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Authors and Affiliations

  1. Department of Nuclear Medicine, Hannover Medical School, Carl Neuberg Str 1, 30625, Hannover, Germany

    James T. Thackeray

  2. Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, University of Montreal Hospital Research Centre (CRCHUM), 900 rue Saint-Denis, Montreal, QC H2X0A9, Canada

    Jean N. DaSilva

  3. Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, 9713 EZ, The Netherlands

    Philip H. Elsinga

Authors
  1. James T. Thackeray
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  2. Jean N. DaSilva
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  3. Philip H. Elsinga
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Corresponding author

Correspondence to Philip H. Elsinga .

Editor information

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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Thackeray, J.T., DaSilva, J.N., Elsinga, P.H. (2015). Tracers for Sympathetic Cardiac Neurotransmission Imaging. 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_5

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  • DOI: https://doi.org/10.1007/978-3-662-45074-1_5

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