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  Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

Song, M., Beyer, L., Kaiser, L., Barthel, H., van Eimeren, T., Marek, K., et al. (2021). Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. Journal of Cerebral Blood Flow and Metabolism, 41(11), 2957-2972. doi:10.1177/0271678X211018904.

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Datensatz-Permalink: https://hdl.handle.net/21.11116/0000-0009-2BE6-4 Versions-Permalink: https://hdl.handle.net/21.11116/0000-000B-22DE-5
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 Urheber:
Song, Mengmeng1, Autor
Beyer, Leonie1, Autor
Kaiser, Lena1, Autor
Barthel, Henryk2, Autor
van Eimeren, Thilo3, 4, 5, 6, Autor
Marek, Ken7, 8, Autor
Nitschmann, Alexander1, Autor
Scheifele, Maximilian1, Autor
Palleis, Carla9, Autor
Respondek, Gesine10, Autor
Kern, Maike1, Autor
Biechele, Gloria1, Autor
Hammes, Jochen4, Autor
Bischof, Gèrard4, Autor
Barbe, Michael5, Autor
Onur, Özgür5, Autor
Jessen, Frank6, 11, 12, Autor
Saur, Dorothee13, Autor
Schroeter, Matthias L.14, 15, 16, 17, Autor           
Rumpf, Jost-Julian13, Autor
Rullmann, Michael2, AutorSchildan, Andreas2, AutorPatt, Marianne2, AutorNeumaier, Bernd3, 4, AutorBarret, Olivier7, 8, 18, AutorMadonia, Jennifer7, 8, AutorRussell, David S7, 8, AutorStephens, Andrew W.19, AutorMueller, Andre19, AutorRoeber, Sigrun20, AutorHerms, Jochen6, 20, AutorBötzel, Kai9, AutorDanek, Adrian9, AutorLevin, Johannes9, 21, 22, AutorClassen, Joseph13, AutorHöglinger, Günter U.10, 21, 23, AutorBartenstein, Peter1, 22, AutorVillemagne, Victor24, 25, 26, AutorDrzezga, Alexander4, 6, AutorSeibyl, John7, 8, AutorSabri, Osama2, AutorBoening, Guido1, AutorZiegler, Sibylle1, AutorBrendel, Matthias1, 22, Autor mehr..
Affiliations:
1Department of Nuclear Medicine, Ludwig Maximilians University Munich, Germany, ou_persistent22              
2Department of Nuclear Medicine, University of Leipzig, Germany, ou_persistent22              
3Cognitive Neuroscience, Institute of Neuroscience and Medicine, Research Center Jülich, Germany, ou_persistent22              
4Department of Nuclear Medicine, University of Cologne, Germany, ou_persistent22              
5Department of Neurology, University Hospital Cologne, Germany, ou_persistent22              
6German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, ou_persistent22              
7InviCRO, LLC, Boston, MA, USA, ou_persistent22              
8Molecular Neuroimaging, A Division of inviCRO, New Haven, CT, USA, ou_persistent22              
9Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
10Center for Neurological Medicine, Hannover Medical School MHH, Germany, ou_persistent22              
11Department of Psychiatry and Psychotherapy, University Hospital Cologne, Germany, ou_persistent22              
12Center for Memory Disorders, University Hospital Cologne, Germany, ou_persistent22              
13Department of Neurology, University Hospital Leipzig, Germany, ou_persistent22              
14Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
15Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Germany, ou_persistent22              
16Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
17German Consortium for Frontotemporal Lobar Degeneration (FTLD), Ulm, Germany, ou_persistent22              
18Laboratoire des Maladies Neurodégénératives, Université Paris-Saclay, France, ou_persistent22              
19Life Molecular Imaging GmbH, Berlin, Germany, ou_persistent22              
20Center for Neuropathology and Prion Research, Ludwig Maximilians University Munich, Germany, ou_persistent22              
21German Center for Neurodegenerative Diseases (DZNE), Munich, Germany, ou_persistent22              
22Munich Cluster for Systems Neurology (SyNergy), Ludwig Maximilians University Munich, Germany, ou_persistent22              
23Department of Neurology, TU Munich, Germany, ou_persistent22              
24Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Australia, ou_persistent22              
25Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia, ou_persistent22              
26Department of Medicine, Austin Health, Heidelberg, Australia, ou_persistent22              

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Schlagwörter: PI-2620; Tau; Affinity; Binding; Kinetic modelling
 Zusammenfassung: The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer's disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [18F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.

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Sprache(n): eng - English
 Datum: 2021-01-312020-08-132021-02-032021-05-272021-11
 Publikationsstatus: Erschienen
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1177/0271678X211018904
Anderer: epub 2021
PMID: 34044665
 Art des Abschluß: -

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Titel: Journal of Cerebral Blood Flow and Metabolism
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: New York : Lippincott Williams & Wilkins
Seiten: - Band / Heft: 41 (11) Artikelnummer: - Start- / Endseite: 2957 - 2972 Identifikator: ISSN: 0271-678X
CoNE: https://pure.mpg.de/cone/journals/resource/954925503202