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To date, no high-affinity tau-PET radiopharmaceutical has been optimized for imaging non-AD tauopathies. Here we show the properties of analogues of a first-in-class 4R-tau lead, [\n                    <jats:sup>18<\/jats:sup>\n                    F]OXD-2115, using ligand-based design. Over 150 analogues of OXD-2115 were synthesized and screened in post-mortem brain tissue for tau affinity against [\n                    <jats:sup>3<\/jats:sup>\n                    H]OXD-2115, and in silico models were used to predict brain uptake. [\n                    <jats:sup>18<\/jats:sup>\n                    F]OXD-2314 was identified as a selective, high-affinity non-AD tau PET radiotracer with favorable brain uptake, dosimetry, and radiometabolite profiles in rats and non-human primate and is being translated for first-in-human PET studies.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-49258-1","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:03:16Z","timestamp":1718373796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Ligand-based design of [18F]OXD-2314 for PET imaging in non-Alzheimer\u2019s disease tauopathies"],"prefix":"10.1038","volume":"15","author":[{"given":"Anton","family":"Lindberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-681X","authenticated-orcid":false,"given":"Emily","family":"Murrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9299-0045","authenticated-orcid":false,"given":"Junchao","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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