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

Leonie Beyer,Matthias Brendel,Kai Bötzel,Günter U Höglinger,Mengmeng Song,Özgür Onur,Kenneth Marek ,Thilo Van Eimeren,Michael Rullmann,Jennifer Madonia,Dorothee Saur,Marianne Patt,Marcus Unterrainer,Bernd Neumaier,Olivier Barret,Jochen Herms,John Seibyl,Jost‐Julian Rumpf ,Peter Bartenstein,Michael T Barbe,Henryk Barthel,Victor L Villemagne ,Sigrun Roeber,Frank Jessen,Chengjie Xiong ,Andreas Schildan,David Russell ,Jochen Hammes,Matthias L Schroeter,Alexander Nitschmann,Carla Palleis,Osama Sabri,Andrew Stephens ,Alexander Drzezga,Joseph Claßen ,Gesine Respondek,Julia Sauerbeck

doi:10.1007/s00259-020-04788-w

Abstract

PurposeSecond-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).MethodsTwenty-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.ResultsHighest 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.ConclusionEarly-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.

Highlights

Tauopathies consist of neurodegenerative diseases including, among others, Alzheimer’s disease (AD), frontotemporal dementia and atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with the connective
The cohort consisted of seven subjects with a most likely diagnosis of AD, 13 subjects with movement disorders and most likely diagnosis of PSP or CBS, one case with most likely frontotemporal dementia, two cases with most likely multi-system atrophy, two cases with most likely Parkinson’s disease, and one case with cognitive impairment of unknown reason
Information on tau-positivity and on the presence of neuronal injury is considered in current diagnosis or research criteria of AD [12, 29] and non-AD tauopathies [30]

Summary

Introduction

Tauopathies consist of neurodegenerative diseases including, among others, Alzheimer’s disease (AD), frontotemporal dementia and atypical parkinsonian syndromes such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with the connectiveEur J Nucl Med Mol Imaging characteristic of misfolded and accumulated tau protein in different parts of the brain [1, 2]. For AD, it has been proposed to classify the disease according to the biomarkers for amyloid, tau and neuronal injury by the A/T/N scheme [12]. In this classification scheme, neuronal injury in the pathological definition can be determined in vivo by three different diagnostic approaches. Atrophy in structural magnetic resonance tomography and total tau in cerebrospinal fluid are considered as well as hypometabolism in 18F-fluorodeoxyglucose ([18F]FDG)PET. This is underpinned by a combined study in prion disease, indicating that metabolic imaging via [18F]FDG correlates with neuropathologic changes including neuronal loss [13]

Objectives

Methods

Results

Discussion

Conclusion