{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:40:27Z","timestamp":1789220427307,"version":"build-2803163510"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","issue":"09","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Fortschr Neurol Psychiatr"],"published-print":{"date-parts":[[2026,9]]},"abstract":"Zusammenfassung<\/jats:title>\n Die differenzialdiagnostische Abkl\u00e4rung neurodegenerativer Erkrankungen,\n insbesondere der Parkinson-Syndrome, stellt trotz verbesserter klinischer\n Kriterien weiterhin eine erhebliche Herausforderung dar. Die\n Positronen-Emissions-Tomographie erm\u00f6glicht die in vivo Darstellung\n pathologischer Proteinaggregate und hat sich damit zu einem wichtigen Werkzeug\n der molekularen Bildgebung entwickelt. W\u00e4hrend die Amyloid-PET bereits klinisch\n etabliert ist, r\u00fccken Tau- und \u03b1-Synuclein-PET zunehmend in den Fokus der\n translationalen Forschung und klinischen Anwendung.Dieser \u00dcbersichtsartikel gibt\n einen aktuellen \u00dcberblick \u00fcber die Entwicklung, Validierung und klinische\n Anwendung von Tau- und \u03b1-Synuclein-PET-Tracern mit besonderem Schwerpunkt auf\n atypischen Parkinson-Syndromen. F\u00fcr die Tau-PET werden isoformspezifische\n Aspekte der Tracerbindung, Unterschiede zwischen Tracern der ersten und zweiten\n Generation sowie in-vitro-, autoradiographische und in-vivo-Validierungsdaten\n diskutiert. Ein besonderer Fokus liegt auf Tracern der zweiten Generation wie\n [18F]PI-2620, die verbesserte Bindungseigenschaften f\u00fcr\n 4R-Tauopathien aufweisen. Dar\u00fcber hinaus werden methodische Aspekte der\n quantitativen Auswertung, einschlie\u00dflich Referenzregionen, Zielregionen und\n dynamischer Akquisitionsprotokolle, dargestellt. Im zweiten Teil des Artikels\n wird der aktuelle Stand der \u03b1-Synuclein-PET zusammengefasst. Erste pr\u00e4klinische\n und klinische Daten zum Tracer [18F]ACI-12589 zeigen eine spezifische\n Bindung an pathologisches \u03b1-Synuclein und erm\u00f6glichen insbesondere bei der\n Multisystematrophie eine klare Abgrenzung gegen\u00fcber Morbus Parkinson und\n gesunden Kontrollen. Dar\u00fcber hinaus werden erste pr\u00e4klinische Entwicklungen von\n TDP-43-PET-Tracern als perspektivische Erweiterung der molekularen Bildgebung\n diskutiert.Zusammenfassend verdeutlicht dieser Review das Potenzial von Tau- und\n \u03b1-Synuclein-PET als komplement\u00e4re molekulare Bildgebungsverfahren zur\n Verbesserung der Differenzialdiagnostik atypischer Parkinson-Syndrome und als\n zuk\u00fcnftige Biomarker f\u00fcr Patientenselektion und Therapiemonitoring in\n krankheitsmodifizierenden Studien.<\/jats:p>","DOI":"10.1055\/a-2823-2465","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T23:46:17Z","timestamp":1774655177000},"page":"371-376","source":"Crossref","is-referenced-by-count":2,"title":["Molekulare Bildgebung von Tau- und \u03b1-Synuclein-Pathologien:\n technische Fortschritte, Herausforderungen und Potenziale"],"prefix":"10.1055","volume":"94","author":[{"given":"Johannes Sebastian","family":"Gn\u00f6rich","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Nuklearmedizin,\n Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Franzmeier","sequence":"additional","affiliation":[{"name":"LMU Klinikum Institut f\u00fcr Schlaganfall- und\n Demenzforschung, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Brendel","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Nuklearmedizin,\n Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1002\/alz.13784","article-title":"The six brain-specific TAU isoforms and their role in Alzheimer's\n disease and related neurodegenerative dementia syndromes","volume":"20","author":"S Buchholz","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1021\/acschemneuro.2c00291","article-title":"Molecular Simulations Reveal Distinct Energetic and Kinetic Binding Properties\n of [(18)F]PI-2620 on Tau Filaments from 3R\/4R and 4R Tauopathies","volume":"13","author":"G K\u00fcnze","year":"2022","journal-title":"ACS Chem Neurosci"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/brain\/awu064","article-title":"Non-invasive assessment of Alzheimer\u2019s disease neurofibrillary pathology using\n 18F-THK5105 PET","volume":"137","author":"N Okamura","year":"2014","journal-title":"Brain"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.jalz.2012.11.008","article-title":"[(18)F]T807, a novel tau positron emission tomography imaging agent for\n Alzheimer's disease","volume":"9","author":"C F Xia","year":"2013","journal-title":"Alzheimers Dement"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"911","DOI":"10.2967\/jnumed.119.236224","article-title":"Tau PET imaging with (18)F-PI-2620 in Patients with Alzheimer Disease and\n Healthy Controls: A First-in-Humans Study","volume":"61","author":"A Mueller","year":"2020","journal-title":"J Nucl Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1021\/acs.jmedchem.6b00166","article-title":"Discovery of 6-(Fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine\n ([18F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for\n Quantification of Neurofibrillary Tangles (NFTs)","volume":"59","author":"A M Walji","year":"2016","journal-title":"Journal of Medicinal Chemistry"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.2967\/jnumed.118.214437","article-title":"Evaluation of (18)F-RO-948 PET for Quantitative Assessment of Tau Accumulation\n in the Human Brain","volume":"59","author":"H Kuwabara","year":"2018","journal-title":"J Nucl Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s41380-022-01875-2","article-title":"Discriminative binding of tau PET tracers PI2620, MK6240 and RO948 in\n Alzheimer's disease, corticobasal degeneration and progressive\n supranuclear palsy brains","volume":"28","author":"M L Malarte","year":"2023","journal-title":"Mol Psychiatry"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"108891","DOI":"10.1016\/j.nucmedbio.2024.108891","article-title":"In vitro evaluation of [(3)H]PI-2620 and structural derivatives in\n non-Alzheimer's tauopathies","volume":"130-131","author":"C Varlow","year":"2024","journal-title":"Nucl Med Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1007\/s00259-019-04397-2","article-title":"Discovery and preclinical characterization of [(18)F]PI-2620, a next-generation\n tau PET tracer for the assessment of tau pathology in Alzheimer's\n disease and other tauopathies","volume":"46","author":"H Kroth","year":"2019","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00401-024-02834-7","article-title":"Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau\n PET signals in individuals with primary tauopathies","volume":"148","author":"L Slemann","year":"2024","journal-title":"Acta Neuropathol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1001\/jamaneurol.2020.2526","article-title":"Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy","volume":"77","author":"M Brendel","year":"2020","journal-title":"JAMA Neurol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1002\/mds.28624","article-title":"Cortical [(18) F]PI-2620 Binding Differentiates Corticobasal Syndrome\n Subtypes","volume":"36","author":"C Palleis","year":"2021","journal-title":"Mov Disord"},{"key":"ref15","first-page":"1754","article-title":"(18)F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear\n Palsy","volume":"63","author":"K Messerschmidt","year":"2022","journal-title":"J Nucl Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"121001","DOI":"10.1016\/j.neuroimage.2025.121001","article-title":"Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in\n [(18)F]PI-2620 PET Scans","volume":"306","author":"T Bauer","year":"2025","journal-title":"Neuroimage"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.2967\/jnumed.123.265856","article-title":"[(18)F]PI-2620 Binding Patterns in Patients with Suspected Alzheimer Disease and\n Frontotemporal Lobar Degeneration","volume":"64","author":"G Blazhenets","year":"2023","journal-title":"J Nucl Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1007\/s00259-025-07199-x","article-title":"Exploring the origins of frequent tau-PET signal in vermal and adjacent\n regions","volume":"52","author":"A Kling","year":"2025","journal-title":"European Journal of Nuclear Medicine and Molecular\n Imaging"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2967\/jnumed.123.265930","article-title":"Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with\n [(18)F]PI-2620","volume":"65","author":"G N Bischof","year":"2024","journal-title":"J Nucl Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.1007\/s00259-024-06741-7","article-title":"Assessment of [(18)F]PI-2620 Tau-PET Quantification via Non-Invasive Automatized\n Image Derived Input Function","volume":"51","author":"M Meindl","year":"2024","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00401-020-02158-2","article-title":"Distribution patterns of tau pathology in progressive supranuclear palsy","volume":"140","author":"G G Kovacs","year":"2020","journal-title":"Acta Neuropathol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1007\/s00259-024-07063-4","article-title":"Early-phase (18)F-Flortaucipir tau-PET as a proxy of brain metabolism in\n Alzheimer's disease: a comparison with (18)F-FDG-PET and early-phase\n amyloid-PET","volume":"52","author":"C Boccalini","year":"2025","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13024-025-00822-3","article-title":"Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau\n accumulation in Alzheimer's disease","volume":"20","author":"N Franzmeier","year":"2025","journal-title":"Mol Neurodegener"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"6750","DOI":"10.1038\/s41467-023-42305-3","article-title":"The \u03b1-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy\n from other neurodegenerative diseases","volume":"14","author":"R Smith","year":"2023","journal-title":"Nat Commun"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1002\/mds.29879","article-title":"Impact of Magnetic Resonance Imaging Markers on the Diagnostic Performance of\n the International Parkinson and Movement Disorder Society Multiple System\n Atrophy Criteria","volume":"39","author":"I Wilkens","year":"2024","journal-title":"Mov Disord"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.2967\/jnumed.116.186403","article-title":"18F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of\n Cognitive Impairment","volume":"58","author":"P T Meyer","year":"2017","journal-title":"Journal of Nuclear Medicine"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"9358","DOI":"10.1038\/s41467-025-64540-6","article-title":"Development of [(18)F]ACI-19626 as a first-in-class brain PET tracer for imaging\n TDP-43 pathology","volume":"16","author":"E Vokali","year":"2025","journal-title":"Nat Commun"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"9357","DOI":"10.1038\/s41467-025-64541-5","article-title":"The potential of TDP-43 PET ligands for a biological diagnosis of TDP-43\n proteinopathies","volume":"16","author":"D J Irwin","year":"2025","journal-title":"Nat Commun"}],"container-title":["Fortschritte der Neurologie \u00b7 Psychiatrie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2823-2465.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:34:43Z","timestamp":1789173283000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2823-2465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":27,"journal-issue":{"issue":"09","published-online":{"date-parts":[[2026,9,11]]},"published-print":{"date-parts":[[2026,9]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2823-2465","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0720-4299","1439-3522"],"issn-type":[{"value":"0720-4299","type":"print"},{"value":"1439-3522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}