¹⁸ F-PI2620 Tau-PET in Progressive Supranuclear Palsy – A Multi-Center Evaluation

Ziel/Aim Progressive supranuclear palsy (PSP) is a 4-repeat (4R) tauopathy and region-specific tau deposits establish the neuropathological diagnosis of “definite PSP” post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers to validate the specific presence of the target before therapy initiation. The novel second generation tau-PET ligand ¹⁸F-PI2620 proved absent off-target binding to monoamine oxidases and high affinity to 3/4R tau in Alzheimer’s disease (AD). The aim of this multicenter-evaluation was to investigate ¹⁸F-PI2620 in patients with suspected 4R tau pathology in clinically diagnosed PSP.

Methodik/Methods 56 patients (70±7y, n = 31 female) with probable or possible PSP [n = 38 Richardson syndrome (PSP-RS)] according to MDS-PSP criteria underwent ¹⁸F-PI2620 PET at four different centers together with 10 healthy controls (HC) and 18 disease controls (n = 8 α-synucleinopathy, n = 10 AD). Multilinear reference tissue modeling with cerebellar reference served for calculation of 0-60 min distribution volume ratios (DVR). DVR data in PSP target regions were compared between PSP, HC, and disease controls, controlled for center, age and gender. Regions with DVR ≥2 standard deviations above HC were binary judged as elevated.

Ergebnisse/Results Strongest elevation of ¹⁸F-PI2620 DVR was observed in the globus pallidus of PSP-RS patients (PSP rating scale: 38±15; range 13-71) when compared to all controls (1.16±0.09 vs. HC: 0.99±0.06, α-syn.: 1.02±0.03, AD: 1.05±0.06). PSP-non-RS patients (PSP rating scale: 26±10; range 11-41) also indicated elevated binding in the globus pallidus (DVR: 1.10±0.11). Binarized quantification revealed at least one positive region for 82 % of PSP-RS and 50 % of PSP-non-RS whereas no positive region was observed for 100 % α-synucleinopathies and 80 % of AD disease controls.

Schlussfolgerungen/Conclusions This multi-center evaluation indicates a value of ¹⁸F-PI2620 to diagnose and differentiate suspected PSP patients, may facilitating earlier and more reliable diagnosis of PSP.