{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:25:05Z","timestamp":1790346305932,"version":"4.1.0"},"reference-count":13,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2023,10]]},"abstract":"The vesicular acetylcholine transporter (VAChT) in the brain is an important presynaptic cholinergic biomarker, and neuroimaging studies of VAChT may provide in vivo information about psychiatric and neurologic conditions including Alzheimer's disease that are not accessible by other methods. The 18<\/jats:sup>F\u2010labeled radiotracer, ((\u2010)\u2010(1\u2010(\u20108\u2010(2\u2010[18<\/jats:sup>F]fluoroethoxy)\u20103\u2010hydroxy\u20101,2,3,4\u2010tetrahydronaphthalen\u20102\u2010yl)piperidin\u20104\u2010yl)(4\u2010fluorophenyl)\u2010methanone ([18<\/jats:sup>F]VAT, 1<\/jats:bold>), was reported as a selective and high affinity ligand for the in vivo imaging of VAChT. The synthesis of [18<\/jats:sup>F]VAT has been reported in a two\u2010step procedure with total 140\u2009min, which includes preparation of 2\u2010[18<\/jats:sup>F]fluoroethyltosylate and alkylation of benzovesamicol (\u2010)\u20105<\/jats:bold> precursor with this radiosynthon using two different automated production modules consecutively. A multiple step synthetic route was employed for the synthesis of stereospecific precursor benzovesamicol (\u2010)\u20105<\/jats:bold>, which is difficult to be adapted for scale\u2010up. To make the production of this tracer more amenable for clinical imaging, we present an improved total synthesis protocol to attain [18<\/jats:sup>F]VAT: (1) a tosylethoxy group being pre\u2010installed tosylate precursor (\u2010)\u20108<\/jats:bold> is synthesized to render a simple one\u2010step radiofluorination under mild conditions; (2) The key optically active intermediate benzovesamicol (\u2010)\u20105<\/jats:bold> was obtained via the regio\u2010 and enantio\u2010enriched ring\u2010opening amination of meso\u2010epoxide 3<\/jats:bold> with 4\u2010phenylpiperidine derivative 2<\/jats:bold> under catalysis of a chiral salenCo(III) catalyst 4b<\/jats:bold>, which dramatically simplifies the synthetic route of the tosylate precursor (\u2010)\u20108<\/jats:bold>. [18<\/jats:sup>F]VAT 1<\/jats:bold> was prepared within ~65\u2009min with desired chemical and radiochemical purities, via a fully automated procedure, using a commercial PET tracer production module. The final drug product was obtained as a sterile, pyrogen\u2010free solution that conforms United States Pharmacopeia (USP) <823> requirements.<\/jats:p>","DOI":"10.1002\/jlcr.4059","type":"journal-article","created":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T06:31:52Z","timestamp":1692858712000},"page":"384-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An improved synthesis of [18<\/sup>F]VAT and its precursor"],"prefix":"10.1002","volume":"66","author":[{"given":"Bao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"Department of Chemistry Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari K.","family":"Akula","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"Department of Chemistry Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doyoung","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiu Fung","family":"Mui","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Slifstein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Parsey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-7281","authenticated-orcid":false,"given":"Wenchao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University Stony Brook New York USA"},{"name":"Department of Chemistry Stony Brook University Stony Brook New York USA"},{"name":"PET Research Core, Renaissance School of Medicine Stony Brook University Stony Brook New York 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