{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:17:15Z","timestamp":1785161835994,"version":"3.55.0"},"reference-count":32,"publisher":"MIT Press","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":281,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["direct.mit.edu"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>[18F]PI-2620 is a second generation tracer that has shown high binding affinity for tau aggregation in Alzheimer\u2019s disease (AD). However, [18F]PI-2620 signal in a large sample spanning the healthy aging and AD clinical spectrum as well as the stability of signal across different acquisition time windows has not yet been examined. Here, amyloid negative (A\u03b2-) cognitively unimpaired (CU; n = 49), amyloid positive (A\u03b2+) CU (n = 37), CU individuals with unknown amyloid status (n = 5), mild cognitive impairment (MCI; n = 14), dementia due to AD (n = 19), and non-AD neurodegenerative disorder (n = 54) participants were scanned with [18F]PI-2620 using a 45\u201375 min and\/or 60\u201390 min acquisition time window. The impact of acquisition time on standardized uptake value ratio (SUVR) magnitude was first quantified with linear mixed models, and in participants and regions with high [18F]PI-2620 signal, SUVRs increased linearly up to 0.04 SUVR with each additional 5 min past injection time. We then accounted for differences in acquisition time using a voxel-wise correction approach and showed high correlations (all r\u2019s \u2265 0.986) between SUVRs calculated from 45\u201375 min data and SUVRs from 60\u201390 min data that were interpolated to the 45\u201375 min scale in 15 participants who were scanned across both time windows. Using real and interpolated 45\u201375 min data, we next examined [18F]PI-2620 signal in Braak regions of interest and an off-target binding region (putamen) in A\u03b2- and A\u03b2+ CU, A\u03b2+ MCI, and A\u03b2+ AD dementia (n = 115) and showed that SUVRs in all Braak regions increased with greater disease severity. Within CU, higher Braak I SUVR was significantly associated with greater CSF pTau-181 (n = 35), and higher SUVRs were significantly associated with worse memory and language (n = 57). Thus, voxel-wise acquisition time corrections can be applied to combine [18F]PI-2620 datasets collected at different post-injection times, and once acquisition time is accounted for, [18F]PI-2620 signal shows the expected increases across the AD spectrum and can be used for detection of early tau elevations.<\/jats:p>","DOI":"10.1162\/imag_a_00329","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:02:33Z","timestamp":1728403353000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":9,"title":["[18F]PI-2620 Tau PET signal across the aging and Alzheimer\u2019s disease clinical spectrum"],"prefix":"10.1162","volume":"2","author":[{"given":"Christina B.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary","family":"Vossler","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"America","family":"Romero","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktorija","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra N.","family":"Trelle","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Winer","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward N.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Zeineh","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Sha","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Khalighi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya V.","family":"Yutsis","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimara P.","family":"Morales","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Anders","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Zaharchuk","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"},{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin I.","family":"Andreasson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony D.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"},{"name":"Department of Psychology, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Poston","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido A.","family":"Davidzon","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Mormino","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, United States"},{"name":"Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"281","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"issue":"12","key":"2025081119004357800_b1","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1007\/s00259-020-04788-w","article-title":"Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury","volume":"47","author":"Beyer","year":"2020","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"issue":"1","key":"2025081119004357800_b2","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13195-021-00880-x","article-title":"Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals","volume":"13","author":"Biel","year":"2021","journal-title":"Alzheimer\u2019s Research & 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brain","volume":"61","author":"Bullich","year":"2020","journal-title":"Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine"},{"issue":"1","key":"2025081119004357800_b7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13195-022-01048-x","article-title":"Evaluation of tau deposition using 18F-PI-2620 PET in MCI and early AD subjects\u2014A MissionAD tau sub-study","volume":"14","author":"Bullich","year":"2022","journal-title":"Alzheimer\u2019s Research & Therapy"},{"issue":"4","key":"2025081119004357800_b8","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/npr2.12281","article-title":"Findings of 18F-PI-2620 tau PET imaging in patients with Alzheimer\u2019s disease and healthy controls in relation to the plasma P-tau181 levels in a Japanese sample","volume":"42","author":"Bun","year":"2022","journal-title":"Neuropsychopharmacology 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palsy","volume":"48","author":"Song","year":"2021","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"issue":"4","key":"2025081119004357800_b32","doi-asserted-by":"crossref","first-page":"fcab190","DOI":"10.1093\/braincomms\/fcab190","article-title":"Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies","volume":"3","author":"Tezuka","year":"2021","journal-title":"Brain Communications"},{"issue":"6","key":"2025081119004357800_b33","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1002\/alz.13022","article-title":"Prospective evaluation of plasma phosphorylated tau in a real-life memory clinic in Thailand","volume":"19","author":"Thanapornsangsuth","year":"2023","journal-title":"Alzheimer\u2019s & Dementia"},{"issue":"5","key":"2025081119004357800_b37","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1007\/s00259-022-06087-y","article-title":"Assessment of perfusion deficit with early 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