{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:16:23Z","timestamp":1788174983191,"version":"build-2803163510"},"reference-count":19,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["2U19NS110456-06"],"award-info":[{"award-number":["2U19NS110456-06"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>A novel brain positron emission tomography (PET) radioligand, [11C]HY-2-15, has potential for imaging alpha-synuclein aggregations in multiple system atrophy and misfolded tau proteins in tauopathies, based on its high binding affinity in disease brain tissue homogenates. Here, we demonstrate that [3H]HY-2-15 has the capability to bind to aggregated alpha-synuclein in multiple system atrophy brain and tau aggregations in progressive supranuclear palsy and corticobasal degeneration brain tissues via in vitro autoradiography study. A first-in-human pilot multicenter clinical study recruited a total of 10 subjects including healthy controls and patients with Parkinson\u2019s disease, multiple system atrophy, or progressive supranuclear palsy. The study revealed that [11C]HY-2-15 has a relatively higher specific uptake in the pallidum and midbrain of patients with progressive supranuclear palsy. Total-body scans performed on the PennPET Explorer showed the radiotracer was cleared by renal excretion. However, the rapid metabolism and low brain uptake resulted in a limited signal of [11C]HY-2-15 in brain.<\/jats:p>","DOI":"10.3390\/cells14151157","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T07:57:24Z","timestamp":1753689444000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pilot Study of [11C]HY-2-15: A Mixed Alpha-Synuclein and Tau PET Radiotracer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2833-7727","authenticated-orcid":false,"given":"Chia-Ju","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3841-1825","authenticated-orcid":false,"given":"Dinahlee","family":"Saturnino Guarino","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3209-1034","authenticated-orcid":false,"given":"Anthony J.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Siderowf","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin K.","family":"Schubert","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9082-8618","authenticated-orcid":false,"given":"Hsiaoju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Perlmutter","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, Washington University, Saint Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7645-2869","authenticated-orcid":false,"given":"Robert H.","family":"Mach","sequence":"additional","affiliation":[{"name":"Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.amjmed.2019.03.001","article-title":"Parkinson\u2019s disease and parkinsonism","volume":"132","author":"Hayes","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-022-00382-6","article-title":"Multiple system atrophy","volume":"8","author":"Poewe","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/bs.irn.2019.10.014","article-title":"Corticobasal degeneration","volume":"149","author":"Saranza","year":"2019","journal-title":"Int. Rev. 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Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40478-018-0552-y","article-title":"Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain","volume":"6","author":"Kovacs","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_14","first-page":"781","article-title":"18F-AV-1451 positron emission tomography in Alzheimer\u2019s disease and progressive supranuclear palsy","volume":"140","author":"Passamonti","year":"2017","journal-title":"Brain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40035-022-00283-4","article-title":"Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy","volume":"11","author":"Visanji","year":"2022","journal-title":"Transl. 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Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s41181-024-00259-x","article-title":"Human biodistribution and radiation dosimetry for the tau tracer [18F]Florzolotau in healthy subjects","volume":"9","author":"Lin","year":"2024","journal-title":"EJNMMI Radiopharm. 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