Annals of Nuclear Medicine

, Volume 6, Issue 1, pp 63–67 | Cite as

Preparation and biodistribution in mice of [11C]carfentanil: A radiopharmaceutical for studying brain μ-opioid receptors by positron emission tomography

  • Hideo Saji
  • Daisuke Tsutsumi
  • Yasuhiro Magata
  • Yasuhiko Iida
  • Junji Konishi
  • Akira Yokoyama


A potent μ-opioid agonist, [11C]carfentanil, was prepared by the methylation of carfentanil carboxylic acid with [11C]methyl iodide in order to study brain μ-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7–7.4 GBq/μmol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5–1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of [11C]carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of [11C]carfentanil by the thalamus and striatum. These results indicate that [11C]carfentanil binds specifically to brain μ-opioid receptors.

Key words

[11C]carfentanil synthesis biodistribution opioid receptor positron emission tomography 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pasternak GW: Multiple morphine and enkephalin receptors and the relief of pain.J Am Med Assn 259: 1362–1367, 1988CrossRefGoogle Scholar
  2. 2.
    Wollemann M: Recent developments in the research of opioid receptor subtype molecular characterization.J Neurochem 54: 1095–1101, 1990PubMedCrossRefGoogle Scholar
  3. 3.
    Frost JJ, Wagner Jr HN, Dannals RF, et al: Imaging opiate receptors in the human brain by positron tomography.J Comput Assist Tomogr 9: 231–236, 1985PubMedCrossRefGoogle Scholar
  4. 4.
    Frost JJ, Mayberg HS, Sadzot B, et al: Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography.J Cereb Blood Flow Metab 10: 484–492, 1990PubMedGoogle Scholar
  5. 5.
    Mayberg HS, Frost JJ: Opiate receptors. In Quantitative Imaging: Neuroreceptors, Neurotransmitters, and Enzymes, Frost JJ, Wagner HN, (eds.), New York, Raven Press, pp 81–95, 1990Google Scholar
  6. 6.
    Sedvall G, Farde L, Kopp J, et al: Visualization of neuroreceptor functions in the living human brain. In Visualization of Brain Functions, Ottoson D, Rostene W, (eds.), New York, Stockton Press, pp 159–165, 1989Google Scholar
  7. 7.
    Kung HF: Radiopharmaceuticals for CNS receptor imaging with SPECT.Nucl Med Biol 17: 85–92, 1990Google Scholar
  8. 8.
    Van Daele PGH, De Bruyn MFL, Boey JM, et al: Synthetic analgesics: N(1-[2-aryl ethyl]-4-substituted 4-piperidinyl)N-arylalkanamides.Arzneim Forsch (Drug Res) 26: 1521–1531, 1976Google Scholar
  9. 9.
    Stahl KD, Bever WV, Janseen P, et al: Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs.Eur J Pharmacol 46: 199–205, 1977PubMedCrossRefGoogle Scholar
  10. 10.
    Titeler M, Lyon RA, Kuhar MJ, et al: μ opiate receptors are selectively labeled by [3H]carfentanil in human and rat brain.Eur J Pharmacol 167: 221–228, 1989PubMedCrossRefGoogle Scholar
  11. 11.
    Frost JJ, Mayberg HS, Fisher RS, et al: Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy.Ann Neurol 23: 231–237, 1988PubMedCrossRefGoogle Scholar
  12. 12.
    Frost JJ, Douglass KH, Mayberg HS, et al: Multi-compartmental analysis of [11C]-carfentaml binding to opiate receptors in humans measured by positron emission tomography.J Cereb Blood Flow Metab 9: 398–409, 1989PubMedGoogle Scholar
  13. 13.
    Pfeiffer A, Pasi A, Mehraein P: Opiate receptor binding sites in human brain.Brain Res 248: 87–96, 1982PubMedCrossRefGoogle Scholar
  14. 14.
    Moshowitz AS, Goodman RR: Autoradiographic distribution of Mu1 and Mu2 opioid binding in the mouse central nervous system.Brain Res 360: 117–129, 1985CrossRefGoogle Scholar
  15. 15.
    Dannals RF, Ravert HT, Frost JJ, et al: Radio-synthesis of an opiate receptor binding radiotracer: [11C]carfentanil.Int J Appl Radial hot 36: 303–306, 1985CrossRefGoogle Scholar
  16. 16.
    Glowinski J, Iversen LL: Regional studies of catecholamines in the rat brain-I. The disposition of [3H]norepinephirine, [3H]dopamine and [3H]dopa in various regions of the brain.J Neurochem 13: 655–669, 1966PubMedCrossRefGoogle Scholar
  17. 17.
    Arnett CD, Shiue C-Y, Wolf AP, et al: Comparison of three18F-labeled butyrophenone neuroleptic drugs in the baboon using positron emission tomography.J Neurochem 44: 835–844, 1985PubMedCrossRefGoogle Scholar
  18. 18.
    Fowler JS, Wolf AP: Positron emitter labeled compounds: priorities and problems. In Positron Emission Tomography and Autoradiography: Principles and Applications for The Brain and Heart, Phelps M, Mazziotta J, Schelbert H, (eds.), New York, Raven Press, pp 391–450, 1986Google Scholar
  19. 19.
    Iwata R, Ido T, Ujiie A, et al: Comparative study of specific activity of [11C]methyl iodine: a search for the source of carrier carbon.Appl Radiat Isot 39: 1–7, 1988CrossRefGoogle Scholar
  20. 20.
    Dannals RF, Ravert HT, Wilson AA: Radiochemistry of tracers for neurotransmitter receptor studies. In Quantitative Imaging: Neuroreceptors, Neurotransmitters, and Enzymes, Frost JJ, Wagner HN, (eds.), New York, Raven Press, pp 19–35, 1990Google Scholar
  21. 21.
    Parterson SJ, Robson LE, Kosterlitz HW: Opioid receptors. In The Peptides: Analysis, Synthesis, Biology, Vol 6, Vdenfriend S, Meienhofer J, (eds.), London, Academic Press, pp 147–189, 1984Google Scholar
  22. 22.
    Pasternak GW, Wood PJ: Minireview: multiple Mu opiate receptors.Life Sci 38: 1889–1898, 1986PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Hideo Saji
    • 1
  • Daisuke Tsutsumi
    • 1
  • Yasuhiro Magata
    • 2
  • Yasuhiko Iida
    • 1
  • Junji Konishi
    • 2
  • Akira Yokoyama
    • 1
  1. 1.Faculty of Pharmaceutical SciencesKyoto UniversityJapan
  2. 2.School of MedicineKyoto UniversityJapan

Personalised recommendations