IMPORTANCE Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.OBJECTIVE To investigate the potential of the novel tau radiotracer 18 F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional study, participants underwent dynamic 18 F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans.

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4‐repeat (~50% of cases) or mixed 3‐repeat/4‐repeat tau isoforms (~25% of cases) or nontauopathies (~25% of cases). Objectives The aim of this single‐center study was to investigate the diagnostic value of the tau PET‐ligand [18F]PI‐2620 in patients with corticobasal syndrome. Methods Forty‐five patients (71.5 ± 7.6 years) with corticobasal syndrome and 14 age‐matched healthy controls underwent [18F]PI‐2620‐PET. Beta‐amyloid status was determined by cerebral β‐amyloid PET and/or CSF analysis. Subcortical and cortical [18F]PI‐2620 binding was quantitatively and visually compared between β‐amyloid‐positive and ‐negative patients and controls. Regional [18F]PI‐2620 binding was correlated with clinical and demographic data. Results Twenty‐four percent (11 of 45) were β‐amyloid‐positive. Significantly elevated [18F]PI‐2620 distribution volume ratios were observed in both β‐amyloid‐positive and β‐amyloid‐negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [18F]PI‐2620 PET positivity was distinctly higher in β‐amyloid‐positive compared with β‐amyloid‐negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [18F]PI‐2620 PET revealed a sensitivity of 91% for β‐amyloid‐positive and of 65% for β‐amyloid‐negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of β‐amyloid status, hemispheric lateralization of [18F]PI‐2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [18F]PI‐2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in β‐amyloid‐positive as well as β‐amyloid‐negative corticobasal syndrome. In corticobasal syndrome, [18F]PI‐2620 may potentially serve for a differential diagnosis and for monitoring disease progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

A BS TRACT: Background: Neuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4-repeat tauopathies. Objectives: The aim of this cross-sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4-repeat tauopathies corticobasal degeneration and progressive supranuclear palsy. Methods: Specific binding of the 18 kDa translocator protein tracer 18 F-GE-180 was determined by serial PET during pharmacological depletion of microglia in a 4-repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group

Purpose Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that earlyphase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [ 18 F]PI-2620 as a potential substitute for [ 18 F]fluorodeoxyglucose ([ 18 F]FDG). Methods Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson's disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [ 18 F]PI-2620 tau-PET (0-60 min p.i.) and static [ 18 F]FDG-PET (30-50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R 1) of [ 18 F]PI-2620-PET were correlated with corresponding quantification of [ 18 F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [ 18 F]PI-2620 tau-PETand [ 18 F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers. Results Highest agreement with [ 18 F]FDG-PET quantification was reached for [ 18 F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5-2.5 min SUVr & R 1) displayed strong agreement in all cortical target regions for global mean (R SUVr 0.76, R R1 = 0.77) and cerebellar normalization (R SUVr 0.68, R R1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [ 18 F]FDG-PET. There were no relevant differences between more and less experienced readers. Conclusion Early-phase imaging of [ 18 F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [ 18 F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.

The novel tau-PET tracer [18F]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 [18F]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. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]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 (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 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 (slope9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [18F]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.