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Attributed to the promising clinical efficacy of xanomeline, an M<jats:sub>1<\/jats:sub>\/M<jats:sub>4<\/jats:sub>\u2010preferring agonist, in patients of schizophrenia and Alzheimer's disease, M<jats:sub>1<\/jats:sub>\u2010 or M<jats:sub>4<\/jats:sub>\u2010selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of <jats:sup>11<\/jats:sup>C\u2010labeled positron emission tomography (PET) ligands based on a validated M<jats:sub>4<\/jats:sub>R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [<jats:sup>11<\/jats:sup>C]VU0467485 and two other ligands were prepared in high radiochemical yields (&gt;30\u2009%, decay\u2010corrected) with high radiochemical purity (&gt;99\u2009%) and high molar activity (&gt;74\u2005GBq\u2009\u03bcmol<jats:sup>\u22121<\/jats:sup>). In vitro autoradiography studies indicated that these three ligands possess moderate\u2010to\u2010high in vitro specific binding to M<jats:sub>4<\/jats:sub>R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.<\/jats:p>","DOI":"10.1002\/cmdc.201800710","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T06:54:39Z","timestamp":1545893679000},"page":"303-309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Synthesis and Preliminary Evaluation of <sup>11<\/sup>C\u2010Labeled VU0467485\/AZ13713945 and Its Analogues for Imaging Muscarinic Acetylcholine Receptor Subtype\u20054"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiaoyun","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Hatori","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology  Chiba 263-8555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsushi","family":"Kumata","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology  Chiba 263-8555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuo","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoteru","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology  Chiba 263-8555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology  Chiba 263-8555 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingzhen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longle","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gangqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Centre for Non-power Nuclear Technology, College of Nuclear Technology &amp; Chemistry and Biology Hubei University of Science and Technology  Xianning China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"},{"name":"Department of Nuclear Medicine and PET\/CT-MRI Center the First Affiliated Hospital of Jinan University &amp; Institute of Molecular and Functional Imaging Jinan University  Guangzhou 510630 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Oklahoma  Norman OK 73019 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Josephson","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Nuclear Medicine and Molecular Imaging Massachusetts General Hospital and Harvard Medical School  55 Fruit Street Boston MA 02114 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaofa","family":"Sun","sequence":"additional","affiliation":[{"name":"Hubei Collaborative Innovation Centre for Non-power Nuclear Technology, College of Nuclear Technology &amp; 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