Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury
Authors: Beyer Leonie , Nitschmann Alexander , Barthel Henryk , van Eimeren Thilo , Unterrainer Marcus , Sauerbeck Julia , Marek Ken , Song Mengmeng , Palleis Carla , Respondek Gesine , Hammes Jochen , Barbe Michael T. , Onur Özgür , Jessen Frank , Saur Dorothee , Schroeter Matthias L. , Rumpf Jost-Julian , Rullmann Michael , Schildan Andreas , Patt Marianne , Neumaier Bernd , Barret Olivier , Madonia Jennifer , Russell David S. , Stephens Andrew W. , Roeber Sigrun , Herms Jochen , Bötzel Kai , Levin Johannes , Classen Joseph , Höglinger Günter U. , Bartenstein Peter , Villemagne Victor , Drzezga Alexander , Seibyl John , Sabri Osama , Brendel Matthias 
Published: April 2020

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 early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [18F]PI-2620 as a potential substitute for [18F]fluorodeoxyglucose ([18F]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 [18F]PI-2620 tau-PET (0–60 min p.i.) and static [18F]FDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R1) of [18F]PI-2620-PET were correlated with corresponding quantification of [18F]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 [18F]PI-2620 tau-PET and [18F]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 [18F]FDG-PET quantification was reached for [18F]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 & R1) displayed strong agreement in all cortical target regions for global mean (RSUVr 0.76, RR1 = 0.77) and cerebellar normalization (RSUVr 0.68, RR1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [18F]FDG-PET. There were no relevant differences between more and less experienced readers.

Conclusion
Early-phase imaging of [18F]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 [18F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.