Binding characteristics of [F-18]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET

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, Gerard; Barbe, Michael; Onur, Ozgur; 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; Botzel, Kai; Danek, Adrian; Levin, Johannes; Classen, Joseph; Höglinger, Günter U.; Bartenstein, Peter; Villemagne, Victor; Drzezga, Alexander; Seibyl, John; Sabri, Osama; Boening, Guido; Ziegler, Sibylle und Brendel, Matthias (2021): Binding characteristics of [F-18]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. In: Journal of Cerebral Blood Flow and Metabolism, Bd. 41, Nr. 11, 0271678X211018904: S. 2957-2972

Abstract

The novel tau-PET tracer [F-18]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 [F-18]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. [F-18]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [F-18]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 (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 SUVR30-60 (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. [F-18]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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0271-678X
• Sprache: Englisch