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Chemistry and Biology of Radiotracers Designed to Target Changes in the Myocardial Sympathetic and Parasympathetic Nervous Systems as a Function of Disease or Treatment

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Atlas of Cardiac Innervation

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Abstract

The parasympathetic nervous system uses chiefly acetylcholine (ACh) as its neurotransmitter, although peptides (such as cholecystokinin) may act on the parasympathetic nervous system as a neurotransmitter. ACh acts on two types of receptors: the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of postganglionic neurons. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.

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References

  1. Zimmer H-G. Otto Loewi and the chemical transmission of vagus stimulation in the heart. Clin Cardiol. 2006;29:135–6.

    Article  PubMed  Google Scholar 

  2. Von Euler US. Some aspects of the clinical physiology of noradrenaline. Scand J Clin Lab Invest. 1952;4:254–62.

    Article  CAS  Google Scholar 

  3. von Euler US. Adrenergic neurotransmitter functions. Science. 1971;173:202–6.

    Article  Google Scholar 

  4. Riemann B, Schäfers M, Law MP, Wichter T, Schober O. Radioligands for imaging myocardial alpha- and beta-adrenoceptors. Nuklearmedizin. 2003;42:4–9.

    CAS  PubMed  Google Scholar 

  5. Elsinga PH, van Waarde A, Vaalburg W. Receptor imaging in the thorax with PET. Eur J Pharmacol. 2004;499:1–13.

    Article  CAS  PubMed  Google Scholar 

  6. Mazière M, Comar D, Godot JM, Collard P, Cepeda C, Naquet R. In vivo characterization of myocardium muscarinic receptors by positron emission tomography. Life Sci. 1981;29:2391–7.

    Article  PubMed  Google Scholar 

  7. Pike VW, Law MP, Osman S, Davenport RJ, Rimoldi O, Giardinà D, Camici PG. Selection, design and evaluation of new radioligands for PET studies of cardiac adrenoceptors. Pharm Acta Helv. 2000;74(2–3):191–200.

    Article  CAS  PubMed  Google Scholar 

  8. Moran NC. The development of beta adrenergic blocking drugs: a retrospective and prospective evaluation. Ann N Y Acad Sci. 1967;139:649–60.

    Article  CAS  PubMed  Google Scholar 

  9. Nanoff C, Freissmuth M, Schüz W. Naunyn schmiedebergs. Arch Pharmacol. 1987;336:519.

    Article  CAS  Google Scholar 

  10. Brady F, Luthra SK, Tochon-Danguy HJ, et al. Asymmetric synthesis of a precursor for the automated radiosynthesis of S-(3′-t-butylamino-2′-hydroxypropoxy)-benzimidazol-2-[11C]one (S-[11C]CGP 12177) as a preferred radioligand for beta-adrenergic receptors. Int J Rad Appl Instrum A. 1991;42:621–8.

    Article  CAS  PubMed  Google Scholar 

  11. Elsinga PH, van Waarde A, Jaeggi KA, Schreiber G, Heldoorn M, Vaalburg W. Synthesis and evaluation of (S)-4-(3-(2′-[11C]isopropylamino)-2-hydroxypropoxy) -2H-benzimidazol −2-one ((S)-[11C]CGP 12388) and (S)-4-(3-((1′-[18 F]-fluoroisopropyl)amino)-2-hydroxypropoxy) -2H- benzimidazol-2-one ((S)-[18 F]fluoro-CGP 12388) for visualization of beta-adrenoceptors with positron emission tomography positron. J Med Chem. 1997;40:3829–35.

    Article  CAS  PubMed  Google Scholar 

  12. Delforge J, Mesangeau D, Dolle F, Merlet P, Loc’h C, Bottlaender M, et al. In vivo quantification and parametric images of the cardiac-adrenergic receptor density. J Nucl Med. 2002;43:215–26.

    CAS  PubMed  Google Scholar 

  13. Tsukamoto T, Morita K, Naya M, et al. Decreased myocardial b-adrenergic receptor density in relation to increased sympathetic tone in patients with nonischemic cardiomyopathy. J Nucl Med. 2007;48:1777–82.

    Article  CAS  PubMed  Google Scholar 

  14. Kudo M, Vera DR, Trudeau WL, Stadalnik RC. Validation of in vivo receptor measurements via in vitro radioassay: technetium-99 m-galactosyl-neoglycoalbumin as prototype model. J Nucl Med. 1991;32(6):1177–82.

    CAS  PubMed  Google Scholar 

  15. National Center for Biotechnology Information. PubChem BioAssay Database. http://pubchem.ncbi.nlm.nih.gov/. Accessed 07/07/2015.

  16. Mazière M, Comar D, Godot JM. In vivo characterization of myocardium muscarinic receptors by positron emission tomography. Life Sci. 1981;7(29):2391–7.

    Article  Google Scholar 

  17. Syrota A, Comar D, Paillotin G, et al. Muscarinic cholinergic receptor in the human heart evidenced under physiological conditions by positron emission tomography. Proc Natl Acad Sci U S A. 1985;82:584–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mazzadi AN, Pineau J, Costes N, Le Bars D, Bonnefoi F, Croisille P, Porcher R, Chevalier P. Muscarinic receptor upregulation in patients with myocardial infarction: a new paradigm. Circ Cardiovasc Imaging. 2009;2:365–72.

    Article  PubMed  Google Scholar 

  19. Prenant C, Barre L, Crouzel C. Synthesis of [11C]QNB. Lab Comp Pharm. 1989;27:1257.

    CAS  Google Scholar 

  20. Varastet M, Brouillet E, Chavoix C, et al. In vivo visualization of central muscarinic receptors using [11C]quinuclidinyl benzilate and positron emission tomography in baboons. Eur J Pharmacol. 1992;213(2):275–84.

    Article  CAS  PubMed  Google Scholar 

  21. Eckelman WC. Design criteria for targeted molecules: Muscarinic cholinergic systems biology. In: Welch MJ, Eckelman WC, editors. Targeted molecular imaging. Boca Raton: CRC Press, Taylor & Francis Group; 2012. p. 388–215.

    Google Scholar 

  22. Barrett JA, Joyal JL, Hillier SM, Maresca KP, Femia FJ, Kronauge JF, Boyd M, Mairs RJ, Babich JW. Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. Cancer Biother Radiopharm. 2010;25:299–308.

    Article  CAS  PubMed  Google Scholar 

  23. Raffel DM. Targeting norepinephrine transporters in cardiac sympathetic nerve terminals. In: Welch MJ, Eckelman WC, editors. Targeted molecular. Imaging. Boca Raton: Taylor & Francis Group, LLC. ISBN: 978-1-4398-4195-2; 2012. pp 305–18.

    Google Scholar 

  24. Krohn KA, Mankoff DA, Muzi M, Link JM, Spence AM. True tracers: comparing FDG with glucose and FLT with thymidine. Nucl Med Biol. 2005;32:663–71.

    Article  CAS  PubMed  Google Scholar 

  25. Raffel DM, Chen W, Jung YW, Jang KS, Gu G, Cozzi NV. Radiotracers for cardiac sympathetic innervation: transport kinetics and binding affinities for the human norepinephrine transporter. Nucl Med Biol. 2013;40:331–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jang KS, Jung YW, Gu G, Koeppe RA, Sherman PS, Quesada CA, Raffel DM. 4-[18 F]Fluoro-m-hydroxyphenethylguanidine: a radiopharmaceutical for quantifying regional cardiac sympathetic nerve density with positron emission tomography. J Med Chem. 2013;56:7312–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eckelman WC, Jones AG, Duatti A, Reba RC. Progress using Tc-99 m radiopharmaceuticals for measuring high capacity sites and low density sites. Drug Discov Today. 2013;18:984–91.

    Article  CAS  PubMed  Google Scholar 

  28. Eckelman WC. Choosing a target for targeted radionuclide therapy using biomarkers to personalize treatment. J Diagn Imaging Ther. 2014;1:103–9.

    Article  Google Scholar 

  29. Werner RA, Rischpler C, Onthank D, et al. Retention kinetics of the 18 F-labeled sympathetic nerve PET tracer LMI1195: comparison with 11C-hydroxyephedrine and 123I-MIBG. J Nucl Med. 2015;56:1429–33.

    Article  CAS  PubMed  Google Scholar 

  30. Vaidyanathan G, McDougald D, Koumarianou E, Choi J, Hens M, Zalutsky MR. Synthesis and evaluation of 4-[18 F]fluoropropoxy-3-iodobenzylguanidine n[18 F]FPOIBG): A novel 18 F-labeled analogue of MIBG. Nucl Med Biol. 2015;42(8):673–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Olshansky B, Sabbah HN, Hauptman PJ, Colucci WS. Parasympathetic nervous system and heart failure: pathophysiology and potential implications for therapy. Circulation. 2008;118:863–71.

    Article  PubMed  Google Scholar 

  32. Caldwell JH and Link JM. Imaging Left Ventricular Muscarinic Receptor Heterogeneity. A Tool to Evaluate Inividuals at Risk for Sudden Death? Circ Cardiovasc Imaging. 2009;2(5):353–5

    Google Scholar 

  33. DeGrado TR, Hutchins GD, Toorongian SA, Wieland DM, Schwaiger M. Myocardial kinetics of carbon-11-meta-hydroxyephedrine: retention mechanisms and effects of norepinephrine. J Nucl Med. 1993;34:1287–93.

    CAS  PubMed  Google Scholar 

  34. Glowniak JV. Cardiac studies with metaiodobenzylguanidine: a critique of methods and interpretation of results. J Nucl Med. 1995;36:2133–7.

    CAS  PubMed  Google Scholar 

  35. Caldwell JH, Kroll K, Li Z, Seymour K, Link JM, Krohn KA. Quantitation of presynaptic cardiac sympathetic function with carbon-11 -meta-hydroxyephedrine. J Nucl Med. 1998;39:1327–34.

    CAS  PubMed  Google Scholar 

  36. Eckelman WC, Lau CY, Neumann RD. Perspective, the one most responsive to change. Nucl Med Biol. 2014;41:297–8.

    Article  CAS  PubMed  Google Scholar 

  37. Eckelman WC, Mankoff DA. Choosing a single target as a biomarker or therapeutic using radioactive probes. Nucl Med Biol. 2015;42:421–5.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Molecular Tracer, Bethesda, MD, USA

    William C. Eckelman

  2. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Vasken Dilsizian

Authors
  1. William C. Eckelman
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  2. Vasken Dilsizian
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Correspondence to William C. Eckelman .

Editor information

Editors and Affiliations

  1. Division of Nuclear Medicine Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Vasken Dilsizian

  2. Division of Cardiology, Mount Sinai Medical Center, New York, New York, USA

    Jagat Narula

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Eckelman, W.C., Dilsizian, V. (2017). Chemistry and Biology of Radiotracers Designed to Target Changes in the Myocardial Sympathetic and Parasympathetic Nervous Systems as a Function of Disease or Treatment. In: Dilsizian, V., Narula, J. (eds) Atlas of Cardiac Innervation. Springer, Cham. https://doi.org/10.1007/978-3-319-45800-7_3

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  • DOI: https://doi.org/10.1007/978-3-319-45800-7_3

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45798-7

  • Online ISBN: 978-3-319-45800-7

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