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While the excellent discriminative power of [18F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (\u223c3\u2005mm isotropic) PET to provide an independent validation for the clinical correlates of [18F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson\u2019s disease, Hoehn\u2013Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson\u2019s disease with 2-year follow-up) cohorts. In the cross-sectional cohort, DAT availability in the putamen and substantia nigra of patients with Parkinson\u2019s disease showed a significant negative association with total motor severity (r = \u22120.59, P = 0.002 for putamen; r = \u22120.46, P = 0.018 for substantia nigra), but not tremor severity. To our knowledge, this is the first observed association between motor severity in Parkinson\u2019s disease and DAT availability in the substantia nigra. The associations with motor severity in most nigrostriatal regions improved if tremor scores were excluded from motor scores. Further, we found significant asymmetry in DAT availability in the putamen (\u223c28% lower DAT availability within the more-affected side of the putamen), and DAT-based asymmetry index for the putamen was correlated with asymmetry in motor severity (r = \u22120.60, P = 0.001). In the longitudinal study, [18F]FE-PE2I PET detected significant annual percentage reduction of DAT availability at the individual level in the putamen (9.7 \u00b1 2.6%), caudate (10.5 \u00b1 3.8%) and ventral striatum (5.5 \u00b1 2.7%), but not the substantia nigra. Longitudinal per cent reduction in DAT availability within the putamen was strongly associated with increase in motor severity (r = 0.91, P = 0.011) at follow-up, demonstrating the high sensitivity of [18F]FE-PE2I PET in tracking longitudinal changes. These results provide further evidence for the utility of [18F]FE-PE2I as an important in vivo PET biomarker in future clinical trials of Parkinson\u2019s disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae345","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T21:00:02Z","timestamp":1727816402000},"source":"Crossref","is-referenced-by-count":12,"title":["Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9073-6270","authenticated-orcid":false,"given":"Praveen","family":"Honhar","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Yale School of Engineering and Applied Sciences, Yale University , New Haven, CT 06511 ,","place":["USA"]},{"name":"Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06520 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of Engineering and Applied Sciences, Yale University , New Haven, CT 06511 ,","place":["USA"]},{"name":"Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06520 ,","place":["USA"]},{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT 06511 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06520 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheila","family":"Najafzadeh","sequence":"additional","affiliation":[{"name":"Radiology and Biomedical Imaging, Yale School of Medicine , New Haven, CT 06520 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