{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:28:23Z","timestamp":1760660903609,"version":"build-2065373602"},"reference-count":17,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EB021155"],"award-info":[{"award-number":["R01EB021155"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A new automated radiosynthesis of [<jats:sup>11<\/jats:sup>C]2\u2010(2,6\u2010difluoro\u20104\u2010((2\u2010(<jats:italic>N<\/jats:italic>\u2010methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([<jats:sup>11<\/jats:sup>C]K2), a radiopharmaceutical for the glutamate \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazole propionic acid (AMPA) receptor, is reported. Although manual syntheses have been described, these are unsuitable for routine production of larger batches of [<jats:sup>11<\/jats:sup>C]K2 for (pre)clinical PET imaging applications. To meet demands for the imaging agent from our functional neuroimaging collaborators, herein, we report a current good manufacturing practice (cGMP)\u2010compliant synthesis of [<jats:sup>11<\/jats:sup>C]K2 using a commercial synthesis module. The new synthesis is fully automated and has been validated for clinical use. The total synthesis time is 33\u2009min from end of bombardment, and the production method provides 2.66\u2009\u00b1\u20090.3\u2009GBq (71.9\u2009\u00b1\u20098.6\u2009mCi) of [<jats:sup>11<\/jats:sup>C]K2 in 97.7\u2009\u00b1\u20090.5% radiochemical purity and 754.1\u2009\u00b1\u2009231.5 TBq\/mmol (20,382.7\u2009\u00b1\u20096256.1\u2009Ci\/mmol) molar activity (<jats:italic>n<\/jats:italic>\u2009=\u20093). Batches passed all requisite quality control testing confirming suitability for clinical use.<\/jats:p>","DOI":"10.1002\/jlcr.4113","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:29:02Z","timestamp":1717720142000},"page":"324-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improved Radiosynthesis and Automation of [<sup>11<\/sup>C]2\u2010(2,6\u2010Difluoro\u20104\u2010((2\u2010(<i>N<\/i>\u2010methylphenylsulfonamido)ethyl)thio)phenoxy)acetamide ([<sup>11<\/sup>C]K2) for Positron Emission Tomography of the Glutamate \u03b1\u2010Amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazole Propionic Acid (AMPA) Receptor"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7271-6567","authenticated-orcid":false,"given":"Jason\u00a0A.","family":"Witek","sequence":"first","affiliation":[{"name":"Department of Radiology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6317-0689","authenticated-orcid":false,"given":"Mami","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Michigan  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradford\u00a0D.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-3024","authenticated-orcid":false,"given":"Allen\u00a0F.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-0450","authenticated-orcid":false,"given":"Peter\u00a0J.\u00a0H.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.37"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.018"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2021.729051"},{"key":"e_1_2_8_3_1","unstructured":"a)J.Takeo S.Yamashita K.Wada andC.Yoshiyuki. \u201cGlutamic Acid Receptor Agonist \u201d WO9625926A1 (1996)."},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-15-05760.1997"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0723-9"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2021.05.009"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81002-3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2022.04.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.1937"},{"key":"e_1_2_8_6_2","unstructured":"b)USP. \u201c<823> Positron Emission Tomography Drugs for Compounding Investigational and Research Uses Radiopharmaceuticals for Positron Emission Tomography.\u201d In:USP 43\u2010NF 38. Rockville: The United States Pharmacopeia Convention;2020."},{"key":"e_1_2_8_7_1","unstructured":"a)T.Takahashi T.Miyazaki T.Suhara M.Higuchi andM.Cho. \u201cNovel Compound That Specifically Binds to AMPA Receptor \u201d WO2017006931A1 (2017)."},{"key":"e_1_2_8_7_2","unstructured":"b)T.Takahashi T.Miyazaki andW.Nakajima. \u201cProphylactic and\/or Therapeutic Agent for Diseases Associated With AMPA Receptors WO2018131662A1 (2018)."},{"key":"e_1_2_8_8_1","unstructured":"\u201cComparison Spectra Can Be found in the Supporting Information.\u201d"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apradiso.2014.01.033"},{"key":"e_1_2_8_10_1","unstructured":"\u201cDuring development and validation of this process we analyzed solvent concentrations for several batches using gas chromatography confirming that residual cleaning solvents like acetone were below ICH limits (and undetectable in most cases). Ethanol is not a residual solvent because it is included in the formulation but ethanol concentrations in the final formulation were found to be 4\u2009\u00b1\u20091% in agreement with our intended formulation.\u201d"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apradiso.2008.08.015"}],"container-title":["Journal of Labelled Compounds and Radiopharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jlcr.4113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:13:09Z","timestamp":1760631189000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jlcr.4113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,6]]},"references-count":17,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/jlcr.4113"],"URL":"https:\/\/doi.org\/10.1002\/jlcr.4113","archive":["Portico"],"relation":{},"ISSN":["0362-4803","1099-1344"],"issn-type":[{"type":"print","value":"0362-4803"},{"type":"electronic","value":"1099-1344"}],"subject":[],"published":{"date-parts":[[2024,6,6]]},"assertion":[{"value":"2024-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}