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Preclinical Evaluations of Cardiac Sympathetic Innervation Radiotracers

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Autonomic Innervation of the Heart

Abstract

Preclinical evaluations of radiotracers designed for imaging cardiac sympathetic innervation have played a key role in the development of this branch of nuclear cardiology. In this chapter, many of the experimental approaches used to characterize the neuronal uptake and retention mechanisms of sympathetic nerve radiotracers are reviewed, from in vitro assays to in vivo imaging studies in animal models. Data from these studies have been critically important in the development of the most optimal radiotracers for cardiac innervation imaging studies in human subjects. They have also provided invaluable insights into the underlying neuronal retention mechanisms of each radiotracer, which are essential to understanding observed changes in the myocardial retention and kinetics of the radiotracer in heart diseases.

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Abbreviations

[11C]-D2-PHEN:

[11C]-(–)-α,α-dideutero-phenylephrine

[11C]-EPI:

[11C]-(–)-epinephrine

[11C]-GMO:

N-[11C]-guanyl-(–)-meta-octopamine

[11C]-mHED:

[11C]-meta-(–)-hydroxyephedrine

[11C]-MHPG:

[11C]-meta-hydroxyphenethylguanidine

[11C]-PHEN:

[11C]-(–)-phenylephrine

[11C]-PHPG:

[11C]-para-hydroxyphenethylguanidine

[123I]-MIBG:

[123I]-metaiodobenzylguanidine

[131I]-RIBA:

[131I]-o-iodobenzyltrimethylammonium iodide

[18F]-4F-MHPG:

4-[18F]-fluoro-meta-hydroxyphenethylguanidine

[3H]-NE:

[3H]-labeled norepinephrine

6-OHDA:

6-hydroxydopamine

C6-hNET:

Cloned human NET (cells)

COMT:

Catechol-O-methyltransferase

DMI:

Desipramine

EMT:

Extraneuronal monoamine transporter

HMG-CoA:

3-hydroxy-3-methylglutaryl-coenzyme A

HPLC:

High-performance liquid chromatography

LAD:

Left anterior descending (artery)

MAO:

Monoamine oxidase

mHED:

(–)-meta-hydroxyephedrine

MIBG:

Metaiodobenzylguanidine

NET:

Norepinephrine transporter

OCT3:

Organic cation transporter 3

PAPS:

Adenosine-3′-phosphate-5′-phosphosulfate

PET:

Positron emission tomography

PHEN:

(–)-phenylephrine

RBC(s):

Red blood cell(s)

RI:

Retention index

ROI:

Region-of-interest

SPECT:

Single photon emission computed tomography

STZ:

Streptozotocin

UDPGA:

Uridine 5′-diphosphoglucuronic acid

VMAT2:

Vesicular monoamine transporter 2

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Authors and Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, 2276 Medical Sciences I Building, SPC 5610, Ann Arbor, MI, 48109, USA

    David M. Raffel PhD

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  1. David M. Raffel PhD
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Correspondence to David M. Raffel PhD .

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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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Raffel, D.M. (2015). Preclinical Evaluations of Cardiac Sympathetic Innervation Radiotracers. 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_10

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  • DOI: https://doi.org/10.1007/978-3-662-45074-1_10

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