18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION

Abstract

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. Eighteen patients (70±6y, n=9 female) with probable or possible PSP Richardson syndrome according to MDS-PSP criteria underwent 18F-PI2620 PET at four different centers together with ten healthy controls and ten disease controls (Multi-system atrophy, Parkinson's disease, and AD). Standardized uptake value ratios (SUVr, 30-60min) of predefined subcortical brain regions were generated using cerebellar scaling. SUVr data were compared between PSP, HC, and disease controls. Statistical parametric mapping (SPM, V12) was performed between PSP and HC. SUVr and SPM data were corrected for different centers. An in vitro pilot autoradiography using 18F-PI2620 incubation of brain slices was performed. Elevated 18F-PI2620 SUVr was observed in PSP patients (PSP rating scale: 40±17; range 13-71) in the globus pallidus (1.34±0.16; p=0.001; d=1.72) and the substantia nigra (1.33±0.13; p=0.002; d=1.52) when compared to HC (1.12±0.09/1.15±0.08). Disease controls showed a similar signal in the globus pallidus (1.12±0.08; p=n.s.) and a moderate elevation in the substantia nigra (1.25±0.10; p=n.s.) when compared to HC. SPM revealed elevated 18F-PI2620 uptake in the globus pallidus, in the substantia nigra, and frontal and parietal cortices (all p<0.001, uncorrected) as compared to HC. Subjects with low disease severity (PSP rating scale ≤30; n=4) already had a significantly elevated 18F-PI2620 uptake in the globus pallidus when compared to HC (1.38±0.13; p=0.001; d=2.32). Preliminary in vitro autoradiography showed distinguishable 18F-PI2620 binding in the globus pallidus of a PSP patient which was however lower when compared to cortical binding in AD.