{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:55:35Z","timestamp":1777794935899,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"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":[[2025,4]]},"abstract":"<jats:p>\n                    This paper describes the preclinical validation of the radioligand [\n                    <jats:sup>11<\/jats:sup>\n                    C]ORM-13070 and its tritiated analog for addressing selectivity and occupancy of the selective alpha-2C adrenergic receptor (\u03b1\n                    <jats:sub>2C<\/jats:sub>\n                    R) antagonist BAY 292 in the cynomolgus brain. BAY 292 is a novel drug candidate being developed for the treatment of obstructive sleep apnea (OSA) via binding to central \u03b1\n                    <jats:sub>2C<\/jats:sub>\n                    R.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    autoradiography studies with sections from non-diseased post-mortem human caudate revealed an excellent specific binding window (&gt;80%) using [\n                    <jats:sup>3<\/jats:sup>\n                    H]ORM-13070. BAY 292 bound to the same binding site as [\n                    <jats:sup>3<\/jats:sup>\n                    H]ORM-13070 and generated a good specific binding signal, with greater selectivity for \u03b1\n                    <jats:sub>2C<\/jats:sub>\n                    R. In non-human primates\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    , [\n                    <jats:sup>11<\/jats:sup>\n                    C]ORM-13070 demonstrated a reversible behavior, with uptake at baseline highest in striatum (putamen, caudate, ventral striatum, and pallidum) and low in the cerebellar cortex, consistent with the known distribution of the \u03b1\n                    <jats:sub>2C<\/jats:sub>\n                    R. A dose dependent increase in receptor occupancy after BAY 292 administration was observed, confirming BBB penetration and target engagement. The estimated EC\n                    <jats:sub>50<\/jats:sub>\n                    for BAY 292 is 33.39\u2009\u00b1\u200911.91\u2009ng\/mL. This study aimed to demonstrate the suitability of [\n                    <jats:sup>11<\/jats:sup>\n                    C]ORM-13070 as a PET-radioligand for the study of \u03b1\n                    <jats:sub>2C<\/jats:sub>\n                    R in the non-human primate brain, and to pave the way for future clinical PET tracer studies with BAY 292.\n                  <\/jats:p>","DOI":"10.1177\/0271678x241291949","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:48:01Z","timestamp":1730357281000},"page":"677-689","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    evaluation of [\n                    <sup>11<\/sup>\n                    C]ORM-13070 as PET ligand for alpha-2C adrenergic receptor occupancy using PET imaging in non-human primates"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-3069","authenticated-orcid":false,"given":"Isabel","family":"Piel","sequence":"first","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian C","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Invicro LLC, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"de la Puente Bethencourt","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Bonsall","sequence":"additional","affiliation":[{"name":"Invicro LLC, Hammersmith Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenii A","family":"Rabiner","sequence":"additional","affiliation":[{"name":"Invicro LLC, Hammersmith Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth R","family":"Zasadny","sequence":"additional","affiliation":[{"name":"Invicro LLC, Needham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4922-9254","authenticated-orcid":false,"given":"Amy","family":"Llopis Amenta","sequence":"additional","affiliation":[{"name":"Invicro LLC, New Haven, CT, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A","family":"Wells","sequence":"additional","affiliation":[{"name":"Invicro LLC, Hammersmith Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Poethko","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Prange","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Delbeck","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/46040"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/cap.2013.0028"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25174017"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/cn1000364"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.113.135574"},{"key":"e_1_3_5_7_2","first-page":"12","article-title":"Amphetamine decreases alpha2C-adrenoceptor binding of [11C]ORM-13070: a PET study in the primate brain","volume":"18","author":"Finnema SJ","year":"2014","unstructured":"Finnema SJ, Hughes ZA, Haaparanta-Solin M, et\u00a0al. Amphetamine decreases alpha2C-adrenoceptor binding of [11C]ORM-13070: a PET study in the primate brain. Int J Neuropsychopharmacol 2014; 18: 12\u201319.","journal-title":"Int J Neuropsychopharmacol"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-014-2782-y"},{"key":"e_1_3_5_9_2","unstructured":"clinicaltrials.gov. NCT00735774 and NCT00829907."},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21798"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-3941-y"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13550-020-00741-y"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/2193-1801-4-S1-L20"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-014-2899-z"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.202201217"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.3595"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/open.201900204"},{"key":"e_1_3_5_18_2","unstructured":"NC3Rs. ARRIVE guidelines https:\/\/arriveguidelines.org\/."},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.03.029"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-3203(98)00091-0"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000038000.34930.4E"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1990.127"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200106000-00002"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.190"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1996.0066"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20520"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(97)90625-8"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)90386-7"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.753977"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1258\/la.2012.011173"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800817h"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.46"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19887781"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-009-1340-5"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241291949","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X241291949","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X241291949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:15:19Z","timestamp":1777493719000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X241291949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,31]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1177\/0271678X241291949"],"URL":"https:\/\/doi.org\/10.1177\/0271678x241291949","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,31]]}}}