{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:11:02Z","timestamp":1792552262810,"version":"4.5.0"},"reference-count":162,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82271447"],"award-info":[{"award-number":["82271447"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Neurodegenerative diseases (NDDs) that are characterized by the accumulation of alpha-synuclein (\u03b1-syn) aggregates in both neurons and the non-neuronal cells of the brain are called synucleinopathies. The most common synucleinopathies includes Parkinson\u2019s disease (PD), Parkinson\u2019s disease dementia (PDD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Significant progress has been made in the development of positron emission tomography (PET) radiotracers for synucleinopathies, yielding several \u03b1-syn tracers that have entered clinical studies. However, selective \u03b1-syn imaging still faces inherent challenges. This review provides a comprehensive overview of the progress in \u03b1-syn PET radiotracers from three angles: Alzheimer\u2019s disease (AD)-derived scaffolds, representative compound scaffolds and analogs, and the identification of \u03b1-syn tracers through high-throughput screening (HTS). We discuss the characteristics, advantages, and limitations of the tracers for preclinical and clinical application. Finally, future directions in the development of radioligands for proteinopathies are discussed. There is no clinical available PET radiotracer for imaging \u03b1-syn aggregates, but these advances have laid a key foundation for non-invasive \u03b1-syn imaging and early diagnosis of synucleinopathies.<\/jats:p>","DOI":"10.3390\/cells14120907","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:37:07Z","timestamp":1750131427000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Development of Positron Emission Tomography Radiotracers for Imaging \u03b1-Synuclein Aggregates"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-4912","authenticated-orcid":false,"given":"Xiaodi","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqiang","family":"Ye","sequence":"additional","affiliation":[{"name":"Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology (SUAT), Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-1472","authenticated-orcid":false,"given":"Zhentao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China"},{"name":"TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of neurodegenerative diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/B978-0-323-98817-9.00032-6","article-title":"Synucleinopathies","volume":"196","author":"Lamotte","year":"2023","journal-title":"Handb. 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