A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis

Antoine Leuzy,Olof Strandberg,Chul H Lyoo,Rik Ossenkoppele,Pedro Rosa-Neto,Philip Insel,Hannah Cho,Gil D Rabinovici,Oskar Hansson,Ruben Smith,Niklas Mattsson-Carlgren,Andréa L Benedet,Tharick A Pascoal,Renaud La Joie

doi:10.1007/s00259-021-05401-4

Abstract

PurposeThis study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer’s disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neurodegenerative diseases.MethodsA total of 1755 participants underwent tau PET using either [18F]flortaucipir (n = 975), [18F]RO948 (n = 493), or [18F]MK6240 (n = 287). SUVR values were calculated across four theory-driven ROIs and several tracer-specific data-driven (hierarchical clustering) regions of interest (ROIs). Diagnostic performance and cut-offs for ROIs were determined using receiver operating characteristic analyses and the Youden index, respectively.ResultsComparable diagnostic performance (area under the receiver operating characteristic curve [AUC]) was observed between theory- and data-driven ROIs. The theory-defined temporal meta-ROI generally performed very well for all three tracers (AUCs: 0.926–0.996). An SUVR value of approximately 1.35 was a common threshold when using this ROI.ConclusionThe temporal meta-ROI can be used for differential diagnosis of dementia patients with [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET with high accuracy, and that using very similar cut-offs of around 1.35 SUVR. This ROI/SUVR cut-off can also be applied across tracers to define tau positivity.

Highlights

In addition to neuritic plaques composed of amyloid-β (Aβ), Alzheimer’s disease (AD) is characterized by tau pathology, largely in the form of paired helical filaments (PHFs) comprising a mixture of three/four-repeat tau isoforms [1]
For [18F]RO948, we included a total of 493 subjects (208 cognitively unimpaired (CU), 143 non-AD, and 142 AD dementia) while for [18F]MK6240 we included a total of 287 subjects (218 CU, 19 non-AD, and 50 AD dementia)
Standardized uptake value ratio (SUVR) values across apriori regions of interest (ROIs) were significantly higher in AD patients as compared to CU individuals and non-AD disorders (P < 0.001)

Summary

Introduction

In addition to neuritic plaques composed of amyloid-β (Aβ), Alzheimer’s disease (AD) is characterized by tau pathology, largely in the form of paired helical filaments (PHFs) comprising a mixture of three/four-repeat tau isoforms [1]. While tau aggregates are present in various non-AD neurodegenerative disorders, including certain variants of frontotemporal lobar degeneration and progressive supranuclear palsy (PSP), these are structurally distinct from those observed in AD [2, 3]. The most widely used tau tracer to date, [18F]flortaucipir [5], has been shown to primarily detect AD-type tau aggregates [6, 7]; as such, tau PET may be most valuable for differentiating AD from non-AD tauopathies and other neurodegenerative disorders. Though tau PET is a relatively recent technique, several novel tracers characterized by improved specificity and dynamic range have recently entered the field, including [18F]RO948 [8] and [18F]MK6240 [9, 10]. While characterized by improved specificity and dynamic range, these tracers show greater meningeal uptake

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