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

Abstract

This 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. A 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. Comparable 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. The 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.