{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T22:34:14Z","timestamp":1770676454613,"version":"3.49.0"},"reference-count":229,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as \u03bc, \u03b4, and \u03ba, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-11C]morphine, -codeine and -heroin did not show significant binding in vivo. [11C]Diprenorphine ([11C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the \u03bc-preferring agonist [11C]carfentanil ([11C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [11C]DPN or [11C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate \u03bc-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of \u03bcORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the \u03b4-preferring endogenous opioid enkephalin, have been used in PET studies of \u03b4ORs, and [11C]GR103545 is validated for studies of \u03baORs. Structures such as [11C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of \u03b4-, \u03ba-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry.<\/jats:p>","DOI":"10.3390\/molecules24224190","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T11:30:17Z","timestamp":1574163017000},"page":"4190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A Survey of Molecular Imaging of Opioid Receptors"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-9621","authenticated-orcid":false,"given":"Paul","family":"Cumming","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, University of Bern, Inselspital, Freiburgstra\u00dfe 18, 3010 Bern, Switzerland"},{"name":"School of Psychology and Counselling and IHBI, Queensland University of Technology, QLD 4059, Brisbane, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-7899","authenticated-orcid":false,"given":"J\u00e1nos","family":"Marton","sequence":"additional","affiliation":[{"name":"<i>ABX<\/i> Advanced Biochemical Compounds, Biomedizinische Forschungsreagenzien GmbH, Heinrich-Glaeser-Strasse 10-14, D-1454 Radeberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-3683","authenticated-orcid":false,"given":"Tuomas O.","family":"Lilius","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-675X","authenticated-orcid":false,"given":"Dag Erlend","family":"Olberg","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Oslo, Norwegian Medical Cyclotron Centre, N-0372 Oslo, Norway and Norwegian Medical Cyclotron Centre Ltd., Sognsvannsveien 20, N-0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University of Bern, Inselspital, Freiburgstra\u00dfe 18, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"ref_1","first-page":"79","article-title":"Constitution of codeine and thebaine","volume":"69-86","author":"Gulland","year":"1925","journal-title":"Mem. 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