[C-11] Carfentanil Binds Preferentially to mu-Opioid Receptor Subtype 1 Compared to Subtype 2
2015 (English)In: Molecular Imaging, ISSN 1535-3508, E-ISSN 1536-0121, Vol. 14, 476-483 p.Article in journal (Refereed) PublishedText
The positron emission tomography (PET) ligand [C-11] carfentanil is a selective agonist for mu-opioid receptors and has been used for studying mu-opioid receptors in the human brain. However, it is unknown if [C-11] carfentanil binding differentiates between subtype receptors mu(1) and mu(2). In this study, we investigated whether mu(1) and mu(2) can be studied separately through receptor subtype-selective inhibition of [C-11] carfentanil by pharmacologic intervention. [C-11] Carfentanil binding characteristics on rat brain sections were assessed either alone or in the presence of the mu-receptor inhibitor cyprodime or the mu(1)-specific inhibitor naloxonazine. [C-11] 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 [C-11] carfentanil has higher affinity and binding potential for mu(1) than for mu(2). [C-11] Carfentanil binding to mu(2) in vivo could not be detected following specific blocking of mu(1), as predicted from the low binding potential for mu(2) as measured in vitro. [C-11] Carfentanil binding is preferential for mu(1) compared to mu(2) in vitro and in vivo. Clinical studies employing [C-11] carfentanil are therefore likely biased to measure mu(1) rather than mu(2).
Place, publisher, year, edition, pages
2015. Vol. 14, 476-483 p.
Radiology, Nuclear Medicine and Medical Imaging Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-271053DOI: 10.2310/7290.2015.00019ISI: 000365597900004PubMedID: 26461068OAI: oai:DiVA.org:uu-271053DiVA: diva2:891084