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DOI: 10.1055/s-0040-1708171
Binding characteristics of 18 F-PI-2620 differentiate the clinically predicted tau isoform in suspected 3/4-repeat and 4-repeat tauopathies
Publikationsverlauf
Publikationsdatum:
08. April 2020 (online)
Ziel/Aim Tau proteins consist of different isoforms, characterized by the number of repeats (R) of their microtubule binding sites. Preliminary evidence suggests that the novel second-generation tau PET tracer 18F-PI-2620 is able to visualize the predominantly 3/4R-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies Corticobasal syndrome (CBS) and Progressive supranuclear palsy (PSP) by PET, but - apart from the obvious topographical differences - likely with different kinetics and magnitude of affinity among them. The aim of this study was to determine whether binding characteristics of 18F-PI-2620 are different between 3/4R- and 4R-tauopathies.
Methodik/Methods We evaluated 14 patients with suspected 3/4R tauopathy and 29 patients with suspected 4R tauopathy (14 CBS, 15 PSP) at two different centers according to current diagnosis criteria. 18F-PI-2620 PET scans were acquired 0-60min p.i. and distribution volume ratios (DVR, cerebellar reference) were calculated. Cortical und subcortical clusters exceeding 20 voxels of elevated DVR (≥ 2.5 SD vs. 10 healthy controls) per region were evaluated by non-invasive kinetic modelling. R1 (perfusion), k2 (clearance), DVR, 30-60 min standard-uptake-value-ratios (SUVr30-60) and the linear slope of SUVr between 10 and 60 min p.i. were compared between 3/4R- and 4R-tauopathies.
Ergebnisse/Results Cortical tau-positive clusters in 4R-tau cases had equal R1 but higher k2 values when compared to 3/4R-tau cases (p < 0.001). Higher mean DVR (1.35±0.19 vs. 1.17±0.60, p < 0.01), higher mean SUVr30-60(1.67±0.33 vs. 1.31±0.22, p < 0.001) and steeper slopes (0.85±0.51 vs. 0.43±0.49, p < 0.001) were observed in cortical clusters of 3/4R-tau cases when compared to 4R-tau cases. Subcortical clusters did not show significant differences.
Schlussfolgerungen/Conclusions 18F-PI-2620 binding characteristics in tau-positive cortical regions differentiate clinically suspected 3/4R-tauopathies from 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tau cases.
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