{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:44:52Z","timestamp":1792788292665,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen","id":[{"id":"https:\/\/ror.org\/05591te55","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Patients with Alzheimer\u2019s disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A\/T\/N classification system. Apart from fluid biomarkers and structural MRI, A\/T\/N assessment incorporates \u03b2-amyloid-PET (A), tau-PET (T), and [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG-PET (N). We evaluated if dynamic features of tau-PET with [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620 allow prediction of \u03b2-amyloid positivity and simultaneous staging of tau and neurodegeneration in individual patients using a single imaging session.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied 129 patients with tauopathies, comprising 47 patients with \u03b2-amyloid-positive 3\/4-repeat tauopathy and 82 patients with \u03b2-amyloid-negative primary 4-repeat tauopathies, alongside 17 healthy controls. Participants underwent 60-minute dynamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620 tau-PET. Kinetic modelling simultaneously provided tracer efflux rate (K2a) as a predictor for \u03b2-amyloid status, distribution volume ratio (DVR) for regional tau burden, and relative perfusion (R1) as a marker of neurodegeneration. These parameters were validated against \u03b2-amyloid-PET, [\n                      <jats:sup>18<\/jats:sup>\n                      F]FDG-PET, volumetric MRI, and cerebrospinal fluid biomarkers using receiver operating characteristic and correlation analyses and visual assessments. [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>K2a<\/jats:sub>\n                      -based prediction of \u03b2-amyloid positivtiy was additionally tested in an independent, clinically heterogeneous validation cohort of 97 individuals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>K2a<\/jats:sub>\n                      differentiated tau isoform compositions despite clinically overlapping presentations and tau-PET patterns, demonstrating reduced cortical tracer clearance in 3\/4-repeat compared with 4-repeat tauopathies. [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>K2a<\/jats:sub>\n                      remained sensitive in individuals with visually negative or low [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>DVR<\/jats:sub>\n                      signals and outperformed both tau burden and perfusion for predicting \u03b2-amyloid status, achieving an area under the curve of 0.99, a positive predictive value of 91.5%, and a negative predictive value of 95.1%. Performance remained robust in the independent validation cohort, with an area under the curve of 0.98, a positive predictive value of 87.9%, and a negative predictive value of 95.3%. [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>DVR<\/jats:sub>\n                      quantified regional tau patterns, with cortical predominance in 3\/4-repeat tauopathy and subcortical involvement in 4-repeat tauopathies. [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620\n                      <jats:sub>R1<\/jats:sub>\n                      exhibited strong quantitative and visual associations with established markers of neurodegeneration. Integration of K2a, DVR, and R1 in disease-specific composite regions enabled individualized three-dimensional A\/T\/N staging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Dynamic [\n                      <jats:sup>18<\/jats:sup>\n                      F]PI-2620 PET imaging facilitates assessment of the \u03b2-amyloid status and regional staging of tau and neurodegeneration during a single acquisition. This one-stop-shop approach may reduce radiation exposure, streamline diagnostic workflows, and facilitate personalized disease profiling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13024-026-00997-3","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:36:44Z","timestamp":1790235404000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic [18F]PI-2620 recording facilitates prediction of \u03b2-amyloid positivity and simultaneous staging of tau and 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All participants or their legally authorized representatives provided written informed consent to participate in the study and to undergo PET imaging.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent covered the use of anonymized imaging and clinical data for scientific publication where required. No directly identifiable individual participant data are presented.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"These authors jointly supervised this work: G\u00fcnter H\u00f6glinger, Nicolai Franzmeier, Matthias Brendel.","order":3,"name":"Ethics","label":"Author information","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A.Dz. reports: research support: Siemens Healthineers, Life Molecular Imaging, GE Healthcare, AVID Radiopharmaceuticals, Sofie, Eisai, Novartis\/AAA, Ariceum Therapeutics; Speaker Honoraria\/Advisory Boards: Siemens Healthineers, Sanofi, GE Healthcare, Biogen, Novo Nordisk, Invicro, Novartis\/AAA, Bayer Vital, Lilly, Peer View Institute for Medical Education, International Atomic Energy Agency: Stock: Siemens Healthineers, Lantheus Holdings, Structured therapeutics, Lilly; Patents: Patent for 18F-JK-PSMA- 7 (Patent No.: EP3765097A1; Date of patent: Jan. 20, 2021). MB is a member of the Neuroimaging Committee of the EANM. MB has received speaker honoraria from Roche, GE Healthcare, Iba, Miltenyi, and Life Molecular Imaging; has advised Life Molecular Imaging, MIAC, Cenos, and GE healthcare; and is currently on the advisory or imaging review boards of AC Immune and ZRO Imaging.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"59"}}