Journal Article

DZNE-2021-00738

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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. ; Eimeren, T.DZNE* ; Marek, K.Extern* ; Nitschmann, A. ; Scheifele, H. M.Extern* ; Palleis, C.Extern* ; Respondek, G.Extern* ; Kern, M. ; Biechele, G. ; Hammes, J. ; Bischof, G. ; Barbe, M. ; Onur, Ö. ; Jessen, F.DZNE* ; Saur, D. ; Schroeter, M. L. ; Rumpf, J.-J. ; Rullmann, M. ; Schildan, A. ; Patt, M. ; Neumaier, B. ; Barret, O. ; Madonia, J. ; Russell, D. S. ; Stephens, A. W. ; Mueller, A. ; Roeber, S. ; Herms, J.DZNE* ; Bötzel, K. ; Danek, A.Extern* ; Levin, J.DZNE* ; Classen, J. ; Höglinger, G. U.DZNE* ; Bartenstein, P. ; Villemagne, V. ; Drzezga, A.DZNE* ; Seibyl, J. ; Sabri, O.Extern* ; Boening, G. ; Ziegler, S. ; Brendel, M.

2021
Sage London

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Please use a persistent id in citations: doi:10.1177/0271678X211018904

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.

Keyword(s): Fluorine Radioisotopes (MeSH) ; Humans (MeSH) ; Image Interpretation, Computer-Assisted: methods (MeSH) ; Neuroimaging: methods (MeSH) ; Positron-Emission Tomography: methods (MeSH) ; Protein Isoforms: analysis (MeSH) ; Radiopharmaceuticals (MeSH) ; Tauopathies: diagnostic imaging (MeSH) ; tau Proteins: analysis (MeSH) ; PI-2620 ; Tau ; affinity ; binding ; kinetic modelling

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Contributing Institute(s):

1. Clinical Dementia Research München (Clinical Dementia Research München)
2. Patient studies cologne (AG Jessen)
3. Coordinator of Clinical Parkinson Research (AG Höglinger 2)
4. Positron Emissions Tomography (PET) (AG Boecker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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