{"doi":"10.1002/mds.70041","title":"Measuring Dopamine Transporter Availability and Synaptic Density in Parkinson's Disease: A Dual‐Tracer Positron Emission Tomography Imaging Study","abstract":"Abstract Background 18 F‐FE‐PE2I is a highly selective dopamine transporter (DAT) positron emission tomography (PET) radioligand, whereas 11 C‐UCB‐J targets synaptic vesicle glycoprotein 2A (SV2A), enabling the assessment of synaptic density. Both tracers show significant alterations in Parkinson's disease (PD) in nigrostriatal regions. However, the extent of overlap between overall synaptic loss and dopaminergic denervation across different disease stages remains unclear. Objective To evaluate similarities and differences between patterns of DAT and SV2A binding in healthy controls (HC) and PD patients at different disease stages. Methods Thirty patients with PD (12 women, age: 65.8 ± 7.1 years) and thirteen HCs (7 women, age: 57.8 ± 5.4 years) underwent PET imaging with 18 F‐FE‐PE2I and 11 C‐UCB‐J on separate days. Patients with PD were also stratified by disease duration into two subgroups (<3 years, n = 10; >6 years, n = 11). Binding potentials ( BP ND ) were quantified in four regions of interest (ROIs): caudate, putamen, ventral striatum (VS), and substantia nigra (SN). Between‐group differences in BP ND were evaluated against HCs for each tracer, and correlations between 18 F‐FE‐PE2I and 11 C‐UCB‐J BP ND were evaluated. Results In HCs, significant correlations were observed between caudate 18 F‐FE‐PE2I and striatal 11 C‐UCB‐J BP ND (caudate, putamen, VS). In PD (full cohort and longer‐duration subgroup), significant correlations emerged between SN 11 C‐UCB‐J and striatal 18 F‐FE‐PE2I. Percent differences between patients with PD and HCs with 18 F‐FE‐PE2I and 11 C‐UCB‐J were similar only in the SN. Conclusions This study examined the relationship between DAT and overall synaptic density in nigrostriatal ROIs in PD using dual‐tracer PET imaging, and there were distinct patterns that vary across disease stages. Understanding the interplay between dopaminergic and presynaptic degeneration in PD could enhance our knowledge of its pathophysiology and contribute to improve diagnosis. © 2025 International Parkinson and Movement Disorder Society.","journal":"Movement Disorders","year":2025,"id":576728,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1026483,"name":"Tommaso Volpi","orcid":"0000-0002-5451-6710","position":1,"is_corresponding":false},{"id":1103052,"name":"Praveen Honhar","orcid":"0000-0001-9073-6270","position":2,"is_corresponding":false},{"id":432449,"name":"Sule Tinaz","orcid":"0000-0003-2220-8278","position":3,"is_corresponding":false},{"id":283734,"name":"Mark Dias","orcid":null,"position":4,"is_corresponding":false},{"id":235256,"name":"Takuya Toyonaga","orcid":"0000-0002-0369-8294","position":5,"is_corresponding":false},{"id":235255,"name":"Mika Naganawa","orcid":"0000-0002-4408-2621","position":6,"is_corresponding":false},{"id":282644,"name":"Jean‐Dominique Gallezot","orcid":"0000-0003-0399-8374","position":7,"is_corresponding":false},{"id":1134847,"name":"Yanghong Yang","orcid":"0000-0002-6816-1252","position":8,"is_corresponding":false},{"id":1324120,"name":"Waleed Ibrahim","orcid":"0000-0001-9640-4090","position":9,"is_corresponding":false},{"id":388498,"name":"Brian Pittman","orcid":"0000-0002-0353-5604","position":10,"is_corresponding":false},{"id":1245043,"name":"Salih Çayır","orcid":"0000-0002-4071-5188","position":11,"is_corresponding":false},{"id":242607,"name":"Rajiv Radhakrishnan","orcid":"0000-0002-8220-655X","position":12,"is_corresponding":false},{"id":648509,"name":"Gustavo A. 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