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

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

Department of Neurology

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2295-2305
Number of pages	11
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	48
Issue number	7
DOIs	https://doi.org/10.1007/s00259-021-05401-4
Publication status	Published - 2021 Jul

Bibliographical note

Funding Information:
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.

Funding Information:
Open access funding provided by Lund University. Work at the authors’ research center was supported by the European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Marianne and Marcus Wallenberg Foundation, the Strategic Research Area MultiPark (Multidisciplinary research in Parkinson disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Parkinson Research Foundation, the Skåne University Hospital Foundation, the Bundy Academy, and the Swedish federal government under the Agreement for Medical Education and Research.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

Radiology Nuclear Medicine and imaging

Access to Document

10.1007/s00259-021-05401-4

Cite this

Leuzy, A., Pascoal, T. A., Strandberg, O., Insel, P., Smith, R., Mattsson-Carlgren, N., Benedet, A. L., Cho, H., Lyoo, C. H., La Joie, R., Rabinovici, G. D., Ossenkoppele, R., Rosa-Neto, P., & Hansson, O. (2021). A multicenter comparison of [¹⁸F]flortaucipir, [¹⁸F]RO948, and [¹⁸F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis. European Journal of Nuclear Medicine and Molecular Imaging, 48(7), 2295-2305. https://doi.org/10.1007/s00259-021-05401-4

@article{c730df3f4062440f9b2d67eaa777f3a8,

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

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{\textquoteright}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.",

author = "Antoine Leuzy and Pascoal, {Tharick A.} and Olof Strandberg and Philip Insel and Ruben Smith and Niklas Mattsson-Carlgren and Benedet, {Andr{\'e}a L.} and Hannah Cho and Lyoo, {Chul H.} and {La Joie}, Renaud and Rabinovici, {Gil D.} and Rik Ossenkoppele and Pedro Rosa-Neto and Oskar Hansson",

note = "Funding Information: 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. Funding Information: Open access funding provided by Lund University. Work at the authors{\textquoteright} research center was supported by the European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Marianne and Marcus Wallenberg Foundation, the Strategic Research Area MultiPark (Multidisciplinary research in Parkinson disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Parkinson Research Foundation, the Sk{\aa}ne University Hospital Foundation, the Bundy Academy, and the Swedish federal government under the Agreement for Medical Education and Research. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jul,

doi = "10.1007/s00259-021-05401-4",

language = "English",

volume = "48",

pages = "2295--2305",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer Verlag",

number = "7",

}

Leuzy, A, Pascoal, TA, Strandberg, O, Insel, P, Smith, R, Mattsson-Carlgren, N, Benedet, AL, Cho, H, Lyoo, CH, La Joie, R, Rabinovici, GD, Ossenkoppele, R, Rosa-Neto, P & Hansson, O 2021, 'A multicenter comparison of [¹⁸F]flortaucipir, [¹⁸F]RO948, and [¹⁸F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis', European Journal of Nuclear Medicine and Molecular Imaging, vol. 48, no. 7, pp. 2295-2305. https://doi.org/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. / Leuzy, Antoine; Pascoal, Tharick A.; Strandberg, Olof et al.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 48, No. 7, 07.2021, p. 2295-2305.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis

AU - Leuzy, Antoine

AU - Pascoal, Tharick A.

AU - Strandberg, Olof

AU - Insel, Philip

AU - Smith, Ruben

AU - Mattsson-Carlgren, Niklas

AU - Benedet, Andréa L.

AU - Cho, Hannah

AU - Lyoo, Chul H.

AU - La Joie, Renaud

AU - Rabinovici, Gil D.

AU - Ossenkoppele, Rik

AU - Rosa-Neto, Pedro

AU - Hansson, Oskar

N1 - Funding Information: 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. Funding Information: Open access funding provided by Lund University. Work at the authors’ research center was supported by the European Research Council, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Marianne and Marcus Wallenberg Foundation, the Strategic Research Area MultiPark (Multidisciplinary research in Parkinson disease) at Lund University, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, the Parkinson Foundation of Sweden, the Parkinson Research Foundation, the Skåne University Hospital Foundation, the Bundy Academy, and the Swedish federal government under the Agreement for Medical Education and Research. Publisher Copyright: © 2021, The Author(s).

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

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