Austin Health

Title
Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET.
Publication Date
2021-05-27
Author(s)
Song, Mengmeng
Beyer, Leonie
Kaiser, Lena
Barthel, Henryk
van Eimeren, Thilo
Marek, Ken
Nitschmann, Alexander
Scheifele, Maximilian
Palleis, Carla
Respondek, Gesine
Kern, Maike
Biechele, Gloria
Hammes, Jochen
Bischof, Gèrard
Barbe, Michael
Onur, Özgür
Jessen, Frank
Saur, Dorothee
Schroeter, Matthias L
Rumpf, Jost-Julian
Rullmann, Michael
Schildan, Andreas
Patt, Marianne
Neumaier, Bernd
Barret, Olivier
Madonia, Jennifer
Russell, David S
Stephens, Andrew W
Mueller, Andre
Roeber, Sigrun
Herms, Jochen
Bötzel, Kai
Danek, Adrian
Levin, Johannes
Classen, Joseph
Höglinger, Günter U
Bartenstein, Peter
Villemagne, Victor L
Drzezga, Alexander
Seibyl, John
Sabri, Osama
Boening, Guido
Ziegler, Sibylle
Brendel, Matthias
Subject
PI-2620
Tau
affinity
binding
kinetic modelling
Type of document
Journal Article
OrcId
0000-0003-4247-184X
0000-0002-9105-2943
0000-0001-8857-5383
0000-0002-9247-2843
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.
Link
Citation
Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 2021; 41(11): 2957-2972
Jornal Title
Journal of Cerebral Blood Flow and Metabolism

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