Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography

J. James Frost, Helen S. Mayberg, Bernard Sadzot, Robert F Dannals, John R. Lever, Hayden T. Ravert, Alan A. Wilson, Henry N. Wagner, Jonathan M Links

Research output: Contribution to journalArticle

Abstract

The kinetics and regional distribution of [11C]carfentanil, a μ-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/ nonspecific ratio) reached near equilibrium at ∼40 min, whereas [11C]diprenorphine showed a linear increase until ∼60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of μ-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-μ. sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the μ sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor sub-types in various diseases. Development of selective tracers for the δ- and κ-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace μ, δ, and κ subtypes, will help offset these limitations.

Original languageEnglish (US)
Pages (from-to)484-492
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume10
Issue number4
StatePublished - 1990

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carfentanil
Diprenorphine
Opioid Receptors
Positron-Emission Tomography
Gyrus Cinguli
Frontal Lobe

Keywords

  • Carfentanil
  • Diprenorphine
  • Opiate receptors
  • Positron emission tomography

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography. / Frost, J. James; Mayberg, Helen S.; Sadzot, Bernard; Dannals, Robert F; Lever, John R.; Ravert, Hayden T.; Wilson, Alan A.; Wagner, Henry N.; Links, Jonathan M.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 10, No. 4, 1990, p. 484-492.

Research output: Contribution to journalArticle

Frost, J. James ; Mayberg, Helen S. ; Sadzot, Bernard ; Dannals, Robert F ; Lever, John R. ; Ravert, Hayden T. ; Wilson, Alan A. ; Wagner, Henry N. ; Links, Jonathan M. / Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography. In: Journal of Cerebral Blood Flow and Metabolism. 1990 ; Vol. 10, No. 4. pp. 484-492.
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AU - Frost, J. James

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AU - Wagner, Henry N.

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AB - The kinetics and regional distribution of [11C]carfentanil, a μ-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/ nonspecific ratio) reached near equilibrium at ∼40 min, whereas [11C]diprenorphine showed a linear increase until ∼60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of μ-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-μ. sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the μ sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor sub-types in various diseases. Development of selective tracers for the δ- and κ-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace μ, δ, and κ subtypes, will help offset these limitations.

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