[11C]Carfentanil Binds Preferentially to μ-Opioid Receptor Subtype 1 Compared to Subtype 2

The positron emission tomography (PET) ligand [(11)C]carfentanil is a selective agonist for μ-opioid receptors and has been used for studying μ-opioid receptors in the human brain. However, it is unknown if [(11)C]carfentanil binding differentiates between subtype receptors μ1 and μ2. In this study, we investigated whether μ1 and μ2 can be studied separately through receptor subtype-selective inhibition of [(11)C]carfentanil by pharmacologic intervention. [(11)C]Carfentanil binding characteristics on rat brain sections were assessed either alone or in the presence of the μ-receptor inhibitor cyprodime or the μ1-specific inhibitor naloxonazine. [(11)C]Carfentanil binding in the living rat brain was similarly studied by small animal PET/computed tomography during baseline conditions or following displacement by cyprodime or naloxonazine. Autoradiography binding studies on rat brain sections demonstrated that [(11)C]carfentanil has higher affinity and binding potential for μ1 than for μ2. [(11)C]Carfentanil binding to μ2 in vivo could not be detected following specific blocking of μ1, as predicted from the low binding potential for μ2 as measured in vitro. [(11)C]Carfentanil binding is preferential for μ1 compared to μ2 in vitro and in vivo. Clinical studies employing [(11)C]carfentanil are therefore likely biased to measure μ1 rather than μ2.