Low Sensitivity of the Positron Emission Tomography Ligand [11C]Diprenorphine to Agonist Opiates

S Hume, AR Lingford-Hughes, V Nataf, E Hirani, R Ahmed, ANT Davies, DJ Nutt

Research output: Contribution to journalArticle (Academic Journal)peer-review

28 Citations (Scopus)


Previously, we reported minimal opioid receptor occupancy following a clinical dose of the µ-opioid agonist, methadone, measured in vivo using positron emission tomography (PET) with [11C]diprenorphine and subsequently used rats to obtain experimental data in support of a high receptor reserve hypothesis (Melichar et al., 2005). Here, we report on further preclinical studies investigating opioid receptor occupancy with oxycodone (µ- and {kappa}-receptor agonist), morphine (µ-receptor agonist), and buprenorphine (partial agonist at the µ-receptor and antagonist at the {delta}- and {kappa}-receptors), each given at antinociceptive doses. In vivo binding of [11C]diprenorphine was not significantly reduced after treatment with the full agonists but was reduced by ~90% by buprenorphine. In addition, given that [11C]diprenorphine is a non-subtype-specific PET tracer, there was no regional variation that might feasibly be interpreted as due to differences in opioid subtype distribution. The data support minimal competition between the high-efficacy agonists and the non-subtype-selective antagonist radioligand and highlight the limitations of [11C]diprenorphine PET to monitor in vivo occupancy. Alternative means may be needed to address clinical issues regarding opioid receptor occupancy that are required to optimize treatment strategies.
Translated title of the contributionLow Sensitivity of the Positron Emission Tomography Ligand [11C]Diprenorphine to Agonist Opiates
Original languageEnglish
Pages (from-to)661 - 667
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume322 (2)
Publication statusPublished - Aug 2007

Bibliographical note

Publisher: American Soc. for Pharmacology & Exp. Therapeutics


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