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

doi:10.1007/s00259-021-05401-4

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

Eur J Nucl Med Mol Imaging. 2021 Jul;48(7):2295-2305. doi: 10.1007/s00259-021-05401-4. Epub 2021 May 27.

Authors

Antoine Leuzy^#¹, Tharick A Pascoal^#^{2

3}, Olof Strandberg⁴, Philip Insel^{4

5}, Ruben Smith^{4

6}, Niklas Mattsson-Carlgren^{4

6

7}, Andréa L Benedet^{2

8}, Hannah Cho⁹, Chul H Lyoo⁹, Renaud La Joie¹⁰, Gil D Rabinovici^{10

11}, Rik Ossenkoppele^{4

12}, Pedro Rosa-Neto^{2

13

14}, Oskar Hansson^{15

16}

Affiliations

¹ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden. antoine.leuzy@med.lu.se.
² Translational Neuroimaging Laboratory, McGill Centre for Studies in Aging, McGill University, Montreal, QC, Canada.
³ Department of Psychiatry and Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
⁴ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
⁵ Department of Psychiatry, University of California, San Francisco, CA, USA.
⁶ Department of Neurology, Skåne University Hospital, Lund, Sweden.
⁷ Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
⁸ CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
⁹ Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹⁰ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
¹¹ Departments of Neurology, Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, USA.
¹² VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
¹³ Montreal Neurological Institute, Montreal, QC, Canada.
¹⁴ Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
¹⁵ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden. oskar.hansson@med.lu.se.
¹⁶ Memory Clinic, Skåne University Hospital, Lund, Sweden. oskar.hansson@med.lu.se.

^# Contributed equally.

Abstract

Purpose: 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.

Methods: 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.

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 [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.

Keywords: PET; Tau; [18F]Flortaucipir; [18F]MK6240; [18F]RO948.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnostic imaging
Carbolines
Cognitive Dysfunction*
Diagnosis, Differential
Humans
Positron-Emission Tomography
tau Proteins

Substances

Carbolines
tau Proteins
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole