Skip to main content
SpringerLink
Log in

Special Problems Associated with the Synthesis of High Specific Activity Carbon-11 Labeled Radiotracers

  • Chapter
New Trends in Radiopharmaceutical Synthesis, Quality Assurance, and Regulatory Control

Abstract

Short-lived positron-emitting radiotracers allow researchers and clinicians access to previously unavailable information regarding problems in physiology, biochemistry, and pharmacology in the living human body. Over the past decade, successes in the application of positron emission tomography (PET) to the non-invasive determination of the spatial distribution and regional concentration of a variety of neurotransmitter binding and uptake sites have followed the successful syntheses of appropriately radiolabeled ligands. This presentation concentrates on some problems associated with the synthesis of these high specific activity carbon-11 labeled radiotracers for PET studies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arnett CD, Shiue C-Y, Wolf AP, Fowler JS, Logan J, Watanabe M (1985): Comparison of three 18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography. J Neurochem 44: 835–844.

    CAS  Google Scholar 

  • Arnett CD, Wolf AP, Shiue C-Y, Fowler JS, MacGregor RR, Christman DR, Smith MR (1987): Improved delineation of human dopamine receptors using [18F]-Nmethylspiroperidol and PET. J Nucl Med 27: 1878–1882.

    Google Scholar 

  • Burns HD, Dannals RF, Langstrom B, Ravert HT, Zemyan SE, Duelfer T, Wong DF, Frost JJ, Kuhar MJ, Wagner HN Jr (1984): (3-N-[11C]Methyl)spiperone, a ligand binding to dopamine receptors: Radiochemical synthesis and biodistribution studies in mice. J Nucl Med 25: 1222–1227.

    Google Scholar 

  • Burns HD, Lever JR, Dannals RF, Frost JJ, Wilson AA, Ravert HT, Subramanian V, Zemyan SE, Langström B, Wagner HN Jr (1984): Synthesis of ligands for imaging opiate receptors by positron emission tomography: Carbon-11 labeled diprenorphine. J Label Compd Radiopharm 21: 1167–1169.

    Google Scholar 

  • Creese I and Snyder SH (1978): [3H]-Spiroperidol labels dopamine and serotonin receptors in rat cerebral cortex and hippocampus. Eur J Pharmacol 49: 201–202.

    Google Scholar 

  • Dannals RF, Langström B, Ravert HT, Wilson AA, Wagner HN Jr (1988): Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]Dexetimide and [11C]levetimide. Appl Radiat Isot 39. Int J Radiat Appl Instrum Part A 291–295.

    Google Scholar 

  • Dannals RF, Ravert HT, Wilson AA, Wagner HN Jr (1986): An improved synthesis of (3N-[11C]methyl)spiperone. Int J Appl Radiat Isot 37, 433–434.

    Google Scholar 

  • Dannals RF, Raven HT, Frost JJ, Wilson AA, Burns HD, and Wagner HN Jr (1985): Radiosynthesis of an opiate receptor binding radiotracer: 11C-carfentanil. Int J Appl Radiat Isot 36: 303–306.

    Article  CAS  Google Scholar 

  • Finn RD, Boothe TE, Vora MM, Hildner JC, Emran AM, Kothari PJ (1984): Syntheses with isotopically labelled carbon. Methyl iodide, formaldehyde, and cyanide. Int J Appl Rad Isot 35, 323–335.

    Article  CAS  Google Scholar 

  • Fowler JS, Arnett CD, Wolf AP, MacGregor RR, Norton EF, Findley AM (1982): Carbon-11 labeled spiroperidol. Synthesis, specific activity determination and biodistribution in mice. J Nucl Med 23, 437–445.

    PubMed  CAS  Google Scholar 

  • Fowler JS, Wolf AP (1986): Positron emitter-labeled compounds: Priorities and problems in Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart, Phelp M, Mazziotta J, and Schelbert H (eds). Raven Press, New York, 1986, pp. 391–450.

    Google Scholar 

  • Frost JJ, Smith AC, and Wagner HN Jr (1986) 3H-diprenorphine is selective for mu opiate receptors in vivo. Life Sci 38: 1597–1606.

    Google Scholar 

  • Frost JJ, Smith AC, Kuhar MJ, Dannals RF, Wagner HN Jr (1987): In vivo binding of 3H-N-methyl-spiperone to dopamine and serotonin receptors. Life Sci 40: 987–995.

    Google Scholar 

  • Frost JJ, Mayberg HS, Sadzot B, Dannals RF, Lever J, Links JM, Ravert HT, Wilson AA, and Wagner HN Jr (1988): Comparison of C-11 diprenorphine and C-11 carfentanil binding to opiate receptors in man by PET. J Nucl Med 29: 796.

    Google Scholar 

  • Haigh JC, Lee LJ, and Schweinsburg RE (1983): Immobilization of polar bears with carfentanil. J Wildl Dig 19: 140–144.

    CAS  Google Scholar 

  • Janssen PA, Niemegeers CJE and Schellekens KHL (1965): Is it possible to predict the clinical effects of neuroleptic drugs from animal data? Arzneim Forsch (Drug Res) 15: 104–117.

    CAS  Google Scholar 

  • Kilbourn MR, Welch MJ, Dence CS, Tewson TJ, Saji H, Maeda M (1984): Carrier-added and no-carrier-added syntheses of fluorine-18 labeled spiroperidol and haloperidol. Inn J Appl Radiat Isot 35, 591–598.

    Article  CAS  Google Scholar 

  • Kock MD and Berger J (1987): Chemical immobilization of free-ranging North American bison in Badlands National Park, South Dakota. J Wildl Dis 23: 625–633.

    PubMed  CAS  Google Scholar 

  • Kohler C and Karlsson-Boethias G (1988): In vivo labelling of rat brain dopamine D2 receptors. Stereospecific blockades by the D2 antagonist raclopride and its enantiomer of 3H-spiperone, 3H-N,N-propylnor-apomorphine and 3H-raclopride binding in the rat brain. J Neural Transm 73: 87–100.

    Google Scholar 

  • Laduron PM, Janssen PE and Leysen JE (1978): Spiperone: a ligand of choice for neuroleptic receptors. 2. Regional distribution and in vivo displacement of neuroleptic drugs. Biochem Pharm 27: 317–321.

    Article  PubMed  CAS  Google Scholar 

  • Lever JR, Dannals RF, Wilson AA, Ravert HT, Wagner HN Jr (1987): Synthesis of carbon-11 labeled diprenorphine: A radioligand for positron emission tomographic studies of opiate receptors. Tetrahedron Letters 28, 4015–4018.

    CAS  Google Scholar 

  • Leysen JE, Gommeren W, and Laduron PM (1978a): Spiperone: A ligand of choice for neuroleptic receptors 1. Kinetics and characteristics of in vitro binding. Biochem Pharm 27: 307–316.

    Article  CAS  Google Scholar 

  • Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM (1978b): Serotonergic component of neuroleptic receptors. erg 272: 168–171.

    CAS  Google Scholar 

  • Luthra SK, Pike VW, Brady F (1985): The preparation of carbon-11 labeled diprenorphine. A new radioligand for the study of the opiate receptor system in vivo. J Chem Soc Chem Commun 1985, 1423–1425.

    Article  Google Scholar 

  • Moerlein SM and Stöcklin G (1984): Specific in vivo binding of 77Br-brombenperidol in rat brain. Life Sci 35: 1357–1363.

    CAS  Google Scholar 

  • Rimland A, Langström B (1987): Synthesis of carbon-11 iodomethylcyclopropane. An interesting alkylating reagent. Appl Radiat Isot 38. Int J Radiat Appl Instrum Part A 949–952.

    Google Scholar 

  • Shiue C-Y, Fowler JS, Wolf AP, Watanabe M, Arnett C (1985): Syntheses and specific activity determinations of no-carrier-added fluorine-18 labeled neuroleptic drugs. J Nucl Med 26, 181–186.

    PubMed  CAS  Google Scholar 

  • Stahl KD, Van Bever W, Janssen P, and Simon EJ (1977): Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs. Eur J Pharm 46: 199–205.

    CAS  Google Scholar 

  • Suehiro M, Dannals RF, Scheffel U, Stathis M, Wilson AA, Ravert HT, Villemagne VL, Sanchez-Roa PM, Wagner HN Jr (1990): In vivo labeling of dopamine D2 receptors with N-11C-methylbenperidol. J Nucl Med 31: 2015–2021.

    Google Scholar 

  • Van Daele PGH, De Bruyn MFL, Boey JM, Sanczuk S, Agten JTM, and Janssen PAJ (1976): Synthetic analgesics: N-(1-[2-arylethyl]-4-substituted 4-piperidinyl) Narylalkanamides. Arzneim Forsch (Drug Res) 26: 1521–1531.

    Google Scholar 

  • Wagner HN Jr, Burns HD, Dannals RF, Wong DF, Langstrom B, Duelfer T, Frost JJ, Ravert HT, Links JM, Rosenbloom S, Lukas SE, Kramer AV, Kuhar MJ (1983): Imaging dopamine receptors in the human brain by positron tomography. Science 221: 1264–1266.

    CAS  Google Scholar 

  • Wolf AP, Redvanly CS (1977): Carbon-11 and radiopharmaceuticals. Int J Appl Rad Isot 28, 29–48.

    Google Scholar 

  • Wong DF, Wagner HN Jr, Dannals RF, Links JM, Frost JJ, Ravert HT, Wilson AA, Rosenbaum AE, Folstein MF, Petronis JD, Douglass KH, Toung JKT, Kuhar MJ (1984): Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 226: 1393–1396.

    CAS  Google Scholar 

  • Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga C, Broussolle EP, Ravert HT, Wilson AA, Toung JKT, Malat J, Snyder SH, Kuhar MJ, Gjedde A (1986): Positron emission tomography reveals elevated brain D2 dopamine receptors in schizophrenia. Science 234, 1558–1563.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    Robert F. Dannals, Hayden T. Ravert, Alan A. Wilson & Henry N. Wagner Jr.

Authors
  1. Robert F. Dannals
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hayden T. Ravert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan A. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Henry N. Wagner Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The University of Texas Health Science Center, Houston, Texas, USA

    Ali M. Emran

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Dannals, R.F., Ravert, H.T., Wilson, A.A., Wagner, H.N. (1991). Special Problems Associated with the Synthesis of High Specific Activity Carbon-11 Labeled Radiotracers. In: Emran, A.M. (eds) New Trends in Radiopharmaceutical Synthesis, Quality Assurance, and Regulatory Control. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0626-7_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0626-7_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0628-1

  • Online ISBN: 978-1-4899-0626-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation