Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury

Abstract

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.

Dual-Phase β-Amyloid PET Captures Neuronal Injury and Amyloidosis in Corticobasal Syndrome

“…Furthermore, the detection accuracy of neuronal injury patterns in the visual analysis did not suffer from the unified FDG-PET control cohort or from a potential detection gap between both modalities, since ICC revealed high levels for all intra-rater analyses. As an outlook, early-phase tau-PET imaging could also serve for detection of neuronal injury in CBS ( Beyer et al, 2020 ), but we note that this modality needs to be evaluated in larger cohorts. Standardizations of perfusion imaging across tracers and analytic methods remain open tasks that need to be addressed by the neuroimaging communities.…”

Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases

“…We therefore applied the novel tau PET tracer 18 F-PI-2620 [12,13] across the spectrum of AD and in older healthy controls. 18 F-PI-2620 has shown initial promise in detecting tau aggregates in patients with AD [12,14,15], as well as high selectivity for 3R/4R tau aggregates [13]. The overall goal was to provide a comprehensive overview of the spatial pattern and magnitude of signal with this novel tau ligand in regions relevant to AD.…”

Feasibility of Short Imaging Protocols for [18F]PI-2620 Tau-PET in Progressive Supranuclear Palsy

“…for AD [16,28]. Our ndings show that dynamic scanning can be reduced to 40 minutes with additional gain of the perfusion phase as a neuronal injury surrogate [24]. When detailed quanti cation is not needed in a pure clinical setting, 20-40 SUVr could also facilitates robust identi cation of AD tau pathology.…”

“…Our data indicate that 0-40 DVR provide highly congruent data when compared to 0-60 DVR, thus a reduction of one third of the scan duration is feasible without relevant loss of performance. Another advantage of dynamic [ 18 F]PI-2620 acquisition is the possibility to acquire early phase or R1 images as a surrogate for neuronal injury [24].…”