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

PURPOSE: This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [(18)F]flortaucipir, [(18)F]RO948, and [(18)F]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. METHODS: A total of 1755 participants underwent tau PET using either [(18)F]flortaucipir (n = 975), [(18)F]RO948 (n = 493), or [(18)F]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. RESULTS: 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. CONCLUSION: The temporal meta-ROI can be used for differential diagnosis of dementia patients with [(18)F]flortaucipir, [(18)F]RO948, and [(18)F]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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05401-4.