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Currently, there is no imaging biomarker suitable for a definitive early diagnosis of \u03b1\u2010synucleinopathies. Although dopaminergic deficits detected with single\u2010photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers can support clinical diagnosis by confirming the presence of dopaminergic neurodegeneration, dopaminergic imaging cannot visualize the preceding disease process, nor distinguish \u03b1\u2010synucleinopathies from tauopathies with dopaminergic neurodegeneration, especially at early symptomatic disease stage when clinical presentation is often overlapping. Aggregated \u03b1\u2010synuclein (\u03b1Syn) could be a suitable imaging biomarker in \u03b1\u2010synucleinopathies, because \u03b1Syn aggregation and therefore, Lewy pathology is evidently an early driver of \u03b1\u2010synucleinopathies pathogenesis. Additionally, several antibodies and small molecule compounds targeting aggregated \u03b1Syn are in development for therapy. However, there is no way to directly measure if or how much they lower the levels of aggregated \u03b1Syn in the brain. There is clearly a paramount diagnostic and therapeutic unmet medical need. To date, aggregated \u03b1Syn and Lewy pathology inclusion bodies cannot be assessed ante\u2010mortem with SPECT or PET imaging because of the suboptimal binding characteristics and\/or physicochemical properties of current radiotracers. The aim of this narrative review is to highlight the suitability of aggregated \u03b1Syn as an imaging biomarker in \u03b1\u2010synucleinopathies, the current limitations with and lessons learned from \u03b1Syn radiotracer development, and finally to propose antibody\u2010based ligands for imaging \u03b1Syn aggregates as a complementary tool rather than an alternative to small molecule ligands. \u00a9 2022 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.28984","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T07:33:34Z","timestamp":1647329614000},"page":"936-948","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["\u03b1\u2010Synuclein Radiotracer Development and <i>In Vivo<\/i> Imaging: Recent Advancements and New 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