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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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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-2BE6-4 Version Permalink: https://hdl.handle.net/21.11116/0000-000D-6AE4-B
Genre: Journal Article

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 Creators:
Song, Mengmeng1, Author
Beyer, Leonie1, Author
Kaiser, Lena1, Author
Barthel, Henryk2, Author
van Eimeren, Thilo3, 4, 5, 6, Author
Marek, Ken7, 8, Author
Nitschmann, Alexander1, Author
Scheifele, Maximilian1, Author
Palleis, Carla9, Author
Respondek, Gesine10, Author
Kern, Maike1, Author
Biechele, Gloria1, Author
Hammes, Jochen4, Author
Bischof, Gèrard4, Author
Barbe, Michael5, Author
Onur, Özgür5, Author
Jessen, Frank6, 11, 12, Author
Saur, Dorothee13, Author
Schroeter, Matthias L.14, 15, 16, 17, Author           
Rumpf, Jost-Julian13, Author
Rullmann, Michael2, AuthorSchildan, Andreas2, AuthorPatt, Marianne2, AuthorNeumaier, Bernd3, 4, AuthorBarret, Olivier7, 8, 18, AuthorMadonia, Jennifer7, 8, AuthorRussell, David S7, 8, AuthorStephens, Andrew W.19, AuthorMueller, Andre19, AuthorRoeber, Sigrun20, AuthorHerms, Jochen6, 20, AuthorBötzel, Kai9, AuthorDanek, Adrian9, AuthorLevin, Johannes9, 21, 22, AuthorClassen, Joseph13, AuthorHöglinger, Günter U.10, 21, 23, AuthorBartenstein, Peter1, 22, AuthorVillemagne, Victor24, 25, 26, AuthorDrzezga, Alexander4, 6, AuthorSeibyl, John7, 8, AuthorSabri, Osama2, AuthorBoening, Guido1, AuthorZiegler, Sibylle1, AuthorBrendel, Matthias1, 22, Author more..
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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Free keywords: PI-2620; Tau; Affinity; Binding; Kinetic modelling
 Abstract: 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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Language(s): eng - English
 Dates: 2021-01-312020-08-132021-02-032021-05-272021-11
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1177/0271678X211018904
Other: epub 2021
PMID: 34044665
 Degree: -

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Project name : -
Grant ID : 390857198
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Funding organization : German Research Foundation (DFG)
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Funding organization : NOMIS Foundation
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Funding organization : VolkswagenStiftung/Lower Saxony Ministry for Science/Petermax-Muller Foundation
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Funding program : -
Funding organization : Helmholtz Association
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Funding program : -
Funding organization : German Parkinson's Association (DPG)

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Title: Journal of Cerebral Blood Flow and Metabolism
Source Genre: Journal
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Publ. Info: New York : Lippincott Williams & Wilkins
Pages: - Volume / Issue: 41 (11) Sequence Number: - Start / End Page: 2957 - 2972 Identifier: ISSN: 0271-678X
CoNE: https://pure.mpg.de/cone/journals/resource/954925503202