Skip to main content Accessibility help
Hostname: page-component-59b7f5684b-npccv Total loading time: 0.281 Render date: 2022-10-04T13:45:38.943Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "displayNetworkTab": true, "displayNetworkMapGraph": false, "useSa": true } hasContentIssue true

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System

Published online by Cambridge University Press:  07 November 2014


In the central nervous system, the neurotransmitter norepinephrine is involved in normal physiology, neuropsychiatric disorders, and the effects of numerous drugs. Although alterations of the central noradrenergic system are involved in the pathophysiology and pharmacotherapy of mood disorders, the basis and nature of these changes remain unresolved. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging agents will be valuable for further elucidating the roles of norepinephrine in health and disease. This review discusses PET and SPECT radioligands that have been developed for the enzymes, receptors, and transporters involved in noradrenergic neurotransmission. Currently, imaging agents that exhibit specific in vivo uptake in the brain have been described for monoamine oxidase A and β-adrenergic receptors, but have not undergone detailed evaluation or experimental application. Based on the successful development and utilization of in vivo imaging agents for elements of the central dopaminergic and serotoninergic systems, PET and SPECT radioligands are expected to serve as new tools for studying the physiology, pathophysiology, and pharmacology of the central noradrenergic system.

Feature Articles
Copyright © Cambridge University Press 2001

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



1. Dahlstrom, A, Fuxe, K. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand. 1964;62;155.Google Scholar
2. Foote, SL, Bloom, FE, Aston-Jones, G. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev. 1983;63:844914.CrossRefGoogle ScholarPubMed
3. Aston-Jones, G, Rajkowski, J, Cohen, J. Role of locus coeruleus in attention and behavioral flexibility. Biol Psychiatry. 1999;46:13091320.CrossRefGoogle ScholarPubMed
4. Tanaka, M, Yoshida, M, Emoto, H, Ishii, H. Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: basic studies. Eur J Pharmacol. 2000;405:397406.CrossRefGoogle ScholarPubMed
5. Guyenet, PG. Central noradrenergic neurons: the autonomic connection. Prog Brain Res. 1991;88:365380.CrossRefGoogle ScholarPubMed
6. Ressler, KJ, Nemeroff, CB. Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry. 1999;46:12191233.CrossRefGoogle ScholarPubMed
7. Southwick, SM, Bremner, JD, Rasmusson, A et al. , Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry. 1999;46:11921204.CrossRefGoogle ScholarPubMed
8. Biederman, J, Spencer, T. Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder. Biol Psychiatry. 1999;46:12341242.CrossRefGoogle Scholar
9. Bremner, JD, Krystal, JH, Southwick, SM, Charney, DS. Noradrenergic mechanisms in stress and anxiety: II. clinical studies. Synapse. 1996;23:3951.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
10. Friedman, JI, Adler, DN, Davis, KL. The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's disease. Biol Psychiatry. 1999;46:12431252.CrossRefGoogle ScholarPubMed
11. Gesi, M, Soldani, P, Giorgi, FS et al. , The role of the locus coeruleus in the development of Parkinson's disease. Neurosci Biobehav Rev. 2000;24:655668.CrossRefGoogle ScholarPubMed
12. Verhoeff, NP. Radiotracer imaging of dopaminergic transmission in neuropsychiatric disorders. Psychopharmacology (Berl). 1999;147:217249.CrossRefGoogle ScholarPubMed
13. Staley, JK, Malison, RT, Innis, RB. Imaging of the serotonergic system: interactions of neuroanatomical and functional abnormalities of depression. Biol Psychiatry. 1998;44:534549.CrossRefGoogle Scholar
14. Van Waarde, A. Measuring receptor occupancy with PET. Curr Pharm Design. 2000:6:15931610.CrossRefGoogle Scholar
15. Votaw, JR. PET image acquisition and analysis. Adv Neurol. 2000;83:6986.Google ScholarPubMed
16. Lake, CR, Chernow, B, Feuerstein, G et al. , The sympathetic nervous system in man: its evaluation and the measurement of plasma NE. In: Ziegler, MG, Lake, CR, eds. Norepinephrine. Baltimore, MD: Williams & Wilkins; 1984:125.Google Scholar
17. Melia, KR, Nestler, EJ, Duman, RS. Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats. Psychopharmacology. 1992;108:2326.CrossRefGoogle ScholarPubMed
18. Biegon, A, Fieldust, S. Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. Synapse. 1992;10:7982.CrossRefGoogle ScholarPubMed
19. Zhu, MY, Klimek, V, Dilley, GE et al. , Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression. Biol Psychiatry. 1999;46:12751286.CrossRefGoogle ScholarPubMed
20. DeJesus, OT, Murali, D, Kitchen, R et al. , Evaluation of 3-[18F]fluoro-alpha-fluoromethyl-p-tyrosine as a tracer for striatal tyrosine hydroxylase activity. Nucl Med Biol. 1994;21:663667.CrossRefGoogle ScholarPubMed
21. Brown, WD, Taylor, MD, Roberts, AD et al. , FluoroDOPA PET shows the non-dopaminergic as well as dopaminergic destinations of levodopa. Neurology. 1999;53:12121218.CrossRefGoogle Scholar
22. Brown, WD, DeJesus, OT, Pyzalski, RW et al. , Localization of trapping of 6-[18F]fluoro-L-m-tyrosine, an aromatic. L-amino acid decarboxylase tracer for PET. Synapse. 1999;34:111123.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
23. DeJesus, OT, Endres, CJ, Shelton, SE et al. , Noninvasive assessment of aromatic L-amino acid decarboxylase activity in aging rhesus monkey brain in vivo. Synapse. 2001;39:5863.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
24. Kilbourn, MR. In vivo radiotracers for vesicular neurotransmitter transporters. Nucl Med Biol. 1997;24:615619.CrossRefGoogle ScholarPubMed
25. Efange, SM. In vivo imaging of the vesicular acetylcholine transporter and the vesicular monoamine transporter. FASEB J. 2000;14:24012413.CrossRefGoogle ScholarPubMed
26. Koeppe, RA, Frey, KA, Kuhl, DE, Kilbourn, MR. Assessment of extrastriatal vesicular monoamine transporter binding site density using stereoisomers of [11C]dihydrotetrabenazine. J Cerebr Blood Flow Metabol. 1999;19:13761384.CrossRefGoogle Scholar
27. Shih, JC, Chen, K. Ridd, MJ. Monoamine oxidase: from genes to behavior. Ann Rev Neurosci. 1999;22:197217.CrossRefGoogle Scholar
28. Owens, MJ. Molecular and cellular mechanisms of antidepressant drugs. Depress Anxiety. 19961997;4:153159.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
29. Bergstrom, M, Westerberg, G, Kihlberg, T, Langstrom, B. Synthesis of some 11C-labelled MAO A inhibitors and their in vivo uptake kinetics in rhesus monkey brain. Nucl Med Biol. 1997;24:381388.CrossRefGoogle ScholarPubMed
30. Mukherjee, J, Yang, ZY. Development of N-[3-(2′, 4′-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropargylamine (18F-fluoroclorgyline) as a potential PET radiotracer for monoamine oxidase-A. Nucl Med Biol. 1999;26:619625.CrossRefGoogle Scholar
31. Rafii, H, Chalon, S, Ombetta, JE et al. , An iodinated derivative of moelobemide as potential radioligand for brain MAO A exploration. Life Sci. 1996;58:11591169.CrossRefGoogle ScholarPubMed
32. Hirata, M, Magata, Y, Ohmomo, Y et al. , Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO A in the brain. Nucl Med Biol. 1995;22:175180.CrossRefGoogle Scholar
33. Meana, JJ, Barturen, F, Garcia-Sevilla, JA. Alpha 2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression. Biol Psychiatry. 1992;31:471490.CrossRefGoogle ScholarPubMed
34. De Paermentier, F, Cheetham, SC, Crompton, MR et al. , Brain beta-adrenoceptor binding sites in antidepressant-free depressed suicide victims. Brain Res. 1990;525:7177.Google Scholar
35. Mann, J, Underwood, M, Arango, V. Postmortem studies of suicide victims. In: Watson, S, ed. Biology of Schizophrenia and Affective Disease. Washington, DC: American Psychiatric Press; 1996:197222.Google Scholar
36. Hosoda, K, Duman, RS. Regulation of beta 1-adrenergic receptor mRNA and lig- and binding by antidepressant treatments and norepinephrine depletion in rat frontal cortex. J Neurochem. 1993;60:13351343.CrossRefGoogle Scholar
37. Law, MP, Osman, S, Pike, VW et al. , Evaluation of [11C]GB67, a novel radioligand for imaging myocardial alpha 1-adrenoceptors with positron emission tomography. Eur J Nucl Med. 2000;27:717.CrossRefGoogle ScholarPubMed
38. Pike, VW, Law, MP, Osman, S et al. , Selection, design and evaluation of new radioligands for PET studies of cardiac adrenoceptors. Pharm Acta Helv. 2000;74:191200.CrossRefGoogle ScholarPubMed
39. Hume, SP, Hirani, E, Opacka-Juffry, J et al. , Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central alpha2-adrenoceptors. Eur J Nucl Med. 2000;27:475484.CrossRefGoogle ScholarPubMed
40. Shiue, C, Pleus, RC, Shiue, GG et al. , Synthesis and biological evaluation of [11C]MK-912 as an alpha2-adrenergic receptor radioligand for PET studies. Nucl Med Biol. 1998;25:127133.CrossRefGoogle Scholar
41. Pleus, RC, Shiue, CY, Shiue, GG et al. , Synthesis and biodistribution of the alpha2-adrenergic receptor antagonist [11C]WY26703: use as a radioligand for positron emission tomography. Receptor. 1992;2:241252.Google Scholar
42. Van Waarde, V, Visser, TJ, Elsinga, PH et al. , Imaging beta-adrenoceptors in the human brain with (S)-1′-[18F]fluorocarazolol. J Nucl Med. 1997;38:934939.Google ScholarPubMed
43. Doze, P, van Waarde, A, Elsinga, PH et al. , Validation of S-1′-[18F]fluorocarazolol for in vivo imaging and quantification of cerebral β-adrenoceptors. Eur J Pharmacol. 1998;353:215226.CrossRefGoogle ScholarPubMed
44. Van Waarde, A, Elsinga, PH, Doze, P et al. , A novel beta-adrenoceptor ligand for positron emission tomography: evaluation in experimental animals. Eur J Pharmacol. 1998;343:289296.CrossRefGoogle ScholarPubMed
45. Visser, TJ, van Waarde, A, Doze, P et al. , Characterization of beta2-adrenoceptors, using the agonist [11C]formoterol and positron emission tomography. Eur J Pharmacol. 1998;361:3541.CrossRefGoogle Scholar
46. Schroeter, S, Apparsundaram, S, Wiley, RG et al. , Immunolocalization of the cocaine- and antidepressant-sensitive 1-norepinephrine transporter. J Compar Neurol. 2000;420:211232.3.0.CO;2-3>CrossRefGoogle Scholar
47. Hattori, N, Schwaiger, M. Metaiodobenzylguanidine scintigraphy of the heart: what have we learnt clinically? Eur J Nucl Med. 2000;27:16.CrossRefGoogle ScholarPubMed
48. Bomanji, J, Moyes, J, Huneidi, AH et al. , Cerebral uptake of MIBG: adrenoceptors visualized? Nucl Med Comm. 1991;12:313.CrossRefGoogle ScholarPubMed
49. Dwamena, BA, Zempel, S, Klopper, JF et al. , Brain uptake of iodine-131 metaiodobenzylguanidine following therapy of malignant pheochromocytoma. Clin Nucl Med. 1998;23:441445.CrossRefGoogle ScholarPubMed
50. Law, MP, Osman, S, Davenport, RJ et al. , Biodistribution and metabolism of [N-methyl-11C]-m-hydroxyephedrine in the rat. Nucl Med Biol. 1997;24:417424.Google Scholar
51. Van Dort, ME, Kim, J, Tluczek, L, Wieland, DM. Synthesis of 11C-labeled desipramine and its metabolite 2-hydroxydesipramine: potential radiotracers for PET studies of the norepinephrine transporter. Nucl Med Biol. 1997;24:707711.CrossRefGoogle ScholarPubMed
52. Lee, CM, Javitch, JA, Snyder, SH. Characterization of [3H]desipramine binding associated with neuronal norepinephrine uptake sites in rat brain membranes. J Neurosci. 1982;2:15151525.CrossRefGoogle ScholarPubMed
53. Haka, MS, Kilbourn, MR. Synthesis and regional mouse brain distribution of [11C]nisoxetine, a norepinephrine uptake inhibitor. Int J Radiol Appl Instr B, Nucl Med Biol. 1989;16:771774.CrossRefGoogle ScholarPubMed
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *