%0 Journal Article %A Susan P. Hume %A Anne R. Lingford-Hughes %A Valerie Nataf %A Ella Hirani %A Rabia Ahmad %A Andrew N. Davies %A David J. Nutt %T Low Sensitivity of the Positron Emission Tomography Ligand [11C]Diprenorphine to Agonist Opiates %D 2007 %R 10.1124/jpet.107.121749 %J Journal of Pharmacology and Experimental Therapeutics %P 661-667 %V 322 %N 2 %X 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 κ-receptor agonist), morphine (μ-receptor agonist), and buprenorphine (partial agonist at the μ-receptor and antagonist at the δ- and κ-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. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/322/2/661.full.pdf