Multicenter Study

. 2021 Jul;48(7):2295-2305.

doi: 10.1007/s00259-021-05401-4. Epub 2021 May 27.

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^#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.

PMID: 34041562
PMCID: PMC8175317
DOI: 10.1007/s00259-021-05401-4

Multicenter Study

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 et al. Eur J Nucl Med Mol Imaging. 2021 Jul.

. 2021 Jul;48(7):2295-2305.

doi: 10.1007/s00259-021-05401-4. Epub 2021 May 27.

Authors

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.

PMID: 34041562
PMCID: PMC8175317
DOI: 10.1007/s00259-021-05401-4

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.

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Conflict of interest statement

Dr. Hansson reported receiving grants from Roche during the conduct of the study as well as grants from Roche, non-financial support from GE Healthcare, and grants from Biogen outside the submitted work. AL, TP, OS, PI, RS, NMC, ALB, HC, CHL, RLJ, GR, RO, and PRN report no conflicts of interest.

Figures

**Fig. 1**
Mean [¹⁸F]flortaucipir (A), [¹⁸F]RO948 (B), and [¹⁸F]MK6240 (C) standardized uptake values ratios (SUVRs) across all participants within diagnostic groups

**Fig. 2**
Distribution of SUVR values for [¹⁸F]flortaucipir, [¹⁸F]RO948, and [¹⁸F]MK6240 across theory-driven ROIs. (A) Entorhinal cortex; (B) Early tau; (C) temporal meta-ROI; (D) neocortical meta-ROI. In each panel, the upper left figure is a representation of the ROI used (i.e., individual FreeSurfer-based regions, displayed on left and right hemispheres); the remaining plots show SUVR values for each tracer across diagnostic groups. The notch in the box-and-whisker plots indicates the 95% confidence interval for the median

**Fig. 3**
Distribution of SUVR values for [¹⁸F]flortaucipir, [¹⁸F]RO948, and [¹⁸F]MK6240 across data-driven ROIs. The notch in the box-and-whisker plots indicates the 95% confidence interval for the median. (A) The regions that best separated AD dementia from CU individuals (parahippocampus and inferior temporal cortex) and those diagnosed with non-AD neurodegenerative disorders (entorhinal cortex, amygdala, parahippocampus, and inferior temporal cortex) using [¹⁸F]flortaucipir PET. (B) The regions that best separated AD dementia from CU individuals (entorhinal cortex and amygdala) and those diagnosed with non-AD neurodegenerative disorders (entorhinal cortex, amygdala, parahippocampus, fusiform gyrus, and inferior temporal cortex) using [¹⁸F]RO948. (C) The regions that best separated AD dementia from CU individuals (fusiform gyrus, inferior temporal cortex, middle temporal gyrus) and those diagnosed with non-AD neurodegenerative disorders (entorhinal cortex, amygdala, the inferior temporal cortex, the banks of the superior temporal sulcus, and the fusiform gyrus) using [¹⁸F]MK6240

See this image and copyright information in PMC

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References

1. Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8:1–13. doi: 10.1016/j.jalz.2011.10.007. - DOI - PMC - PubMed
1. Goedert M. Tau filaments in neurodegenerative diseases. FEBS Lett. 2018;592:2383–2391. doi: 10.1002/1873-3468.13108. - DOI - PubMed
1. Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24:1121–1159. doi: 10.1146/annurev.neuro.24.1.1121. - DOI - PubMed
1. Leuzy A, Chiotis K, Lemoine L, Gillberg PG, Almkvist O, Rodriguez-Vieitez E, et al. Tau PET imaging in neurodegenerative tauopathies-still a challenge. Mol Psychiatry. 2019;24:1112–1134. doi: 10.1038/s41380-018-0342-8. - DOI - PMC - PubMed
1. Marquie M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015;78:787–800. doi: 10.1002/ana.24517. - DOI - PMC - PubMed

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

Affiliations

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

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