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

  • Robert F. Dannals
  • Hayden T. Ravert
  • Alan A. Wilson
  • Henry N. WagnerJr.

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.

Keywords

Positron Emission Tomography High Performance Liquid Chromatography Positron Emission Tomography Study High Specific Activity Opiate Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 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.Google Scholar
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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.CrossRefGoogle Scholar
  9. 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.CrossRefGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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
  12. 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
  13. 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
  14. 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
  15. Haigh JC, Lee LJ, and Schweinsburg RE (1983): Immobilization of polar bears with carfentanil. J Wildl Dig 19: 140–144.Google Scholar
  16. 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.Google Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.CrossRefGoogle Scholar
  23. Leysen JE, Niemegeers CJE, Tollenaere JP, Laduron PM (1978b): Serotonergic component of neuroleptic receptors. erg 272: 168–171.Google Scholar
  24. 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.CrossRefGoogle Scholar
  25. Moerlein SM and Stöcklin G (1984): Specific in vivo binding of 77Br-brombenperidol in rat brain. Life Sci 35: 1357–1363.Google Scholar
  26. 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
  27. 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.PubMedGoogle Scholar
  28. 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.Google Scholar
  29. 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
  30. 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
  31. 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.Google Scholar
  32. Wolf AP, Redvanly CS (1977): Carbon-11 and radiopharmaceuticals. Int J Appl Rad Isot 28, 29–48.Google Scholar
  33. 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.Google Scholar
  34. 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.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Robert F. Dannals
    • 1
  • Hayden T. Ravert
    • 1
  • Alan A. Wilson
    • 1
  • Henry N. WagnerJr.
    • 1
  1. 1.Division of Nuclear MedicineThe Johns Hopkins Medical InstitutionsBaltimoreUSA

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