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Song, Mengmeng; Beyer, Leonie; Kaiser, Lena; Barthel, Henryk; Eimeren, Thilo van; 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 ORCID: 0000-0003-4247-184X; Madonia, Jennifer; Russell, David S. ORCID: 0000-0002-9105-2943; Stephens, Andrew W.; Mueller, Andre; Roeber, Sigrun; Herms, Jochen; Bötzel, Kai; Danek, Adrian ORCID: 0000-0001-8857-5383; Levin, Johannes; Classen, Joseph; Höglinger, Günter U.; Bartenstein, Peter; Villemagne, Victor; Drzezga, Alexander; Seibyl, John; Sabri, Osama; Boening, Guido; Ziegler, Sibylle; Brendel, Matthias ORCID: 0000-0002-9247-2843 (2021): Binding characteristics of 18FPI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. In: Journal of Cerebral Blood Flow & Metabolism, Vol. 41, No. 11: pp. 2957-2972
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Abstract

The novel tau-PET tracer 18FPI-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 18FPI-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. 18FPI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. 18FPI-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. 18FPI-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.