{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:44:25Z","timestamp":1777794265581,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>\n                    Previous work found that [\n                    <jats:sup>11<\/jats:sup>\n                    C]deschloroclozapine ([\n                    <jats:sup>11<\/jats:sup>\n                    C]DCZ) is superior to [\n                    <jats:sup>11<\/jats:sup>\n                    C]clozapine ([\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ) for imaging Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). This study used PET to quantitatively and separately measure the signal from transfected receptors, endogenous receptors\/targets, and non-displaceable binding in other brain regions to better understand this superiority. A genetically-modified muscarinic type-4 human receptor (hM\n                    <jats:sub>4<\/jats:sub>\n                    Di) was injected into the right amygdala of a male rhesus macaque. [\n                    <jats:sup>11<\/jats:sup>\n                    C]DCZ and [\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ PET scans were conducted 2\u201324\u2009months later. Uptake was quantified relative to the concentration of parent radioligand in arterial plasma at baseline (n\u2009=\u20093 scans\/radioligand) and after receptor blockade (n\u2009=\u20093 scans\/radioligand). Both radioligands had greater uptake in the transfected region and displaceable uptake in other brain regions. Displaceable uptake was not uniformly distributed, perhaps representing off-target binding to endogenous receptor(s). After correction, [\n                    <jats:sup>11<\/jats:sup>\n                    C]DCZ signal was 19% of that for [\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ, and background uptake was 10% of that for [\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ. Despite stronger [\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ binding, the signal-to-background ratio for [\n                    <jats:sup>11<\/jats:sup>\n                    C]DCZ was almost two-fold greater than for [\n                    <jats:sup>11<\/jats:sup>\n                    C]CLZ. Both radioligands had comparable DREADD selectivity. All reference tissue models underestimated signal-to-background ratio in the transfected region by 40%\u201350% for both radioligands. Thus, the greater signal-to-background ratio of [\n                    <jats:sup>11<\/jats:sup>\n                    C]DCZ was due to its lower background uptake.\n                  <\/jats:p>","DOI":"10.1177\/0271678x211007949","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T01:45:07Z","timestamp":1618451107000},"page":"2571-2582","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["[\n                    <sup>11<\/sup>\n                    C]deschloroclozapine is an improved PET radioligand for quantifying a human muscarinic DREADD expressed in monkey brain"],"prefix":"10.1177","volume":"41","author":[{"given":"Xuefeng","family":"Yan","sequence":"first","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Telu","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4495-8811","authenticated-orcid":false,"given":"Rachel M","family":"Dick","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeih-San","family":"Liow","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Zanotti-Fregonara","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl L","family":"Morse","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lester S","family":"Manly","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L","family":"Gladding","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stal","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Lerchner","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging, National institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-0174","authenticated-orcid":false,"given":"Takafumi","family":"Minamimoto","sequence":"additional","affiliation":[{"name":"Department of Functional Brain Imaging, National institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sami S","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B","family":"Innis","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor W","family":"Pike","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-1540","authenticated-orcid":false,"given":"Barry J","family":"Richmond","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-6832","authenticated-orcid":false,"given":"Mark AG","family":"Eldridge","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"bibr1-0271678X211007949","first-page":"S265","volume":"30","author":"Armbruster B","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"bibr2-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700293104"},{"key":"bibr3-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4192"},{"key":"bibr4-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2703"},{"key":"bibr5-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.014"},{"key":"bibr6-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.08.003"},{"key":"bibr7-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0661-3"},{"key":"bibr8-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1279-16.2016"},{"key":"bibr9-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12236-z"},{"key":"bibr10-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13605"},{"key":"bibr11-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2475"},{"key":"bibr12-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22116-z"},{"key":"bibr13-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.7b00079"},{"key":"bibr14-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600493"},{"key":"bibr15-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41088-2"},{"key":"bibr16-0271678X211007949","unstructured":"Synthia a. compact radiochemistry system for automated production of radiopharmaceuticals. In:\n                      TRIUMF: Proceedings of the VIth Workshop on Targetry and Target Chemistry\n                      , Vancouver, British Columbia, 17\u201319 August 1995."},{"key":"bibr17-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.1779"},{"key":"bibr18-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8043(96)00177-7"},{"key":"bibr19-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/0969-8043(93)90035-9"},{"key":"bibr20-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108730"},{"key":"bibr21-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.30.3.314"},{"key":"bibr22-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600830718"},{"key":"bibr23-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000038000.34930.4E"},{"key":"bibr24-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1109\/TAC.1974.1100705"},{"key":"bibr25-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1186\/s40658-017-0197-0"},{"key":"bibr26-0271678X211007949","first-page":"520","volume":"47","author":"Zoghbi SS","year":"2006","journal-title":"J Nucl Med"},{"key":"bibr27-0271678X211007949","unstructured":"Weber DA, Eckerman KF, Dillman LT, et\u00a0al.\n                      MIRD: radionuclide data and decay schemes\n                      . New York: Society of Nuclear Medicine, 1989."},{"key":"bibr28-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.202"},{"key":"bibr29-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.114.146027"},{"key":"bibr30-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)90279-6"},{"key":"bibr31-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903020104"},{"key":"bibr32-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30346-X"},{"key":"bibr33-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(20)30255-8"},{"key":"bibr34-0271678X211007949","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-017-0334-8"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X211007949","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X211007949","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X211007949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:13:19Z","timestamp":1777493599000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X211007949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,14]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1177\/0271678X211007949"],"URL":"https:\/\/doi.org\/10.1177\/0271678x211007949","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,14]]}}}