Binding characteristics of [ <sup>18</sup> F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET
Mengmeng Song, Leonie Beyer, Lena Kaiser, Henryk Barthel, Thilo van Eimeren, Kenneth Marek, Alexander Nitschmann, Maximilian Scheifele, Carla Palleis, Gesine Respondek, Maike Kern, Gloria Biechele, Jochen Hammes, Gérard N. Bischof, Michael T. Barbe, Oezguer A. Onur, Frank Jessen, Dorothee Saur, Matthias L. Schroeter, Jost‐Julian Rumpf, Michael Rullmann, Andreas Schildan, Marianne Patt, Bernd Neumaier, Olivier Barret, Jennifer Madonia, David Russell, Andrew Stephens, André Mueller, Sigrun Roeber, Jochen Herms, Kai Bötzel, Adrian Danek, Johannes Levin, Joseph Claßen, Günter U. Höglinger, Peter Bartenstein, Victor L. Villemagne, Alexander Drzezga, John Seibyl, Osama Sabri, Guido Boening, Sibylle Ziegler, Matthias Brendel
Abstract
The novel tau-PET tracer [ 18 F]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 [ 18 F]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. [ 18 F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [ 18 F]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 (SUVR 30-60 ) 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 (R1 SRTM : 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2 SRTM : 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 SUVR 30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope 9-60 : 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [ 18 F]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.