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Sex differences in off-target binding using tau positron emission tomography

Smith, Ruben LU ; Strandberg, Olof LU ; Leuzy, Antoine LU ; Betthauser, Tobey J. ; Johnson, Sterling C. ; Pereira, Joana B. LU and Hansson, Oskar LU orcid (2021) In NeuroImage: Clinical 31.
Abstract

Purpose: Off-target binding in the skull and meninges is observed in some subjects undergoing tau positron emission tomography (PET) and could potentially differ between men and women. In this study we elucidate sex differences in tau off-target binding using three different tau PET tracers. Methods: 541 cognitively unimpaired amyloid-β negative participants underwent tau PET using [18F]flortaucipir (n = 165), [18F]RO948 (n = 189) and [18F]MK6240 (n = 187). Baseline SUVR-values were compared between females and males at the voxel level and using a region-of-interest (ROI) encompassing the skull/meninges. In addition, we assessed the cross-sectional relationship between baseline skull/meninges SUVR and... (More)

Purpose: Off-target binding in the skull and meninges is observed in some subjects undergoing tau positron emission tomography (PET) and could potentially differ between men and women. In this study we elucidate sex differences in tau off-target binding using three different tau PET tracers. Methods: 541 cognitively unimpaired amyloid-β negative participants underwent tau PET using [18F]flortaucipir (n = 165), [18F]RO948 (n = 189) and [18F]MK6240 (n = 187). Baseline SUVR-values were compared between females and males at the voxel level and using a region-of-interest (ROI) encompassing the skull/meninges. In addition, we assessed the cross-sectional relationship between baseline skull/meninges SUVR and age and assessed change in skull/meningeal SUVR values over time in a subsample with longitudinal data (n = 63). Results: Voxel-wise analysis showed higher meningeal off-target binding in women compared to men across all three tracers. The SUVRs in the skull/meningeal ROI were highest using [18F]RO948, followed by [18F]MK6240 and [18F]flortaucipir (p < 0.001). For all tracers, females showed higher skull/meningeal ROI retention (mean SUVR ± SD [18F]flortaucipir: 0.82 ± 0.14; [18F]RO948: 1.26 ± 0.30; [18F]MK6240: 1.09 ± 0.19) compared to men ([18F]flortaucipir: 0.70 ± 0.11; [18F]RO948: 1.10 ± 0.24; [18F]MK6240: 0.97 ± 0.17) (p < 0.001). For [18F]flortaucipir and [18F]RO948, off-target binding in the skull/meninges decreased with age. Conclusion: There is an effect of sex on off-target retention in the meninges/skull across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Off-target binding, PET, Sex differences, Tau
in
NeuroImage: Clinical
volume
31
article number
102708
publisher
Elsevier
external identifiers
  • scopus:85107796295
  • pmid:34091353
ISSN
2213-1582
DOI
10.1016/j.nicl.2021.102708
language
English
LU publication?
yes
id
b1e9120d-e8a0-4615-abd4-cd4011f34b65
date added to LUP
2021-07-20 10:16:58
date last changed
2024-09-21 22:39:50
@article{b1e9120d-e8a0-4615-abd4-cd4011f34b65,
  abstract     = {{<p>Purpose: Off-target binding in the skull and meninges is observed in some subjects undergoing tau positron emission tomography (PET) and could potentially differ between men and women. In this study we elucidate sex differences in tau off-target binding using three different tau PET tracers. Methods: 541 cognitively unimpaired amyloid-β negative participants underwent tau PET using [<sup>18</sup>F]flortaucipir (n = 165), [<sup>18</sup>F]RO948 (n = 189) and [<sup>18</sup>F]MK6240 (n = 187). Baseline SUVR-values were compared between females and males at the voxel level and using a region-of-interest (ROI) encompassing the skull/meninges. In addition, we assessed the cross-sectional relationship between baseline skull/meninges SUVR and age and assessed change in skull/meningeal SUVR values over time in a subsample with longitudinal data (n = 63). Results: Voxel-wise analysis showed higher meningeal off-target binding in women compared to men across all three tracers. The SUVRs in the skull/meningeal ROI were highest using [<sup>18</sup>F]RO948, followed by [<sup>18</sup>F]MK6240 and [<sup>18</sup>F]flortaucipir (p &lt; 0.001). For all tracers, females showed higher skull/meningeal ROI retention (mean SUVR ± SD [<sup>18</sup>F]flortaucipir: 0.82 ± 0.14; [<sup>18</sup>F]RO948: 1.26 ± 0.30; [<sup>18</sup>F]MK6240: 1.09 ± 0.19) compared to men ([<sup>18</sup>F]flortaucipir: 0.70 ± 0.11; [<sup>18</sup>F]RO948: 1.10 ± 0.24; [<sup>18</sup>F]MK6240: 0.97 ± 0.17) (p &lt; 0.001). For [<sup>18</sup>F]flortaucipir and [<sup>18</sup>F]RO948, off-target binding in the skull/meninges decreased with age. Conclusion: There is an effect of sex on off-target retention in the meninges/skull across [<sup>18</sup>F]flortaucipir, [<sup>18</sup>F]RO948, and [<sup>18</sup>F]MK6240 tau PET tracers.</p>}},
  author       = {{Smith, Ruben and Strandberg, Olof and Leuzy, Antoine and Betthauser, Tobey J. and Johnson, Sterling C. and Pereira, Joana B. and Hansson, Oskar}},
  issn         = {{2213-1582}},
  keywords     = {{Alzheimer's disease; Off-target binding; PET; Sex differences; Tau}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{NeuroImage: Clinical}},
  title        = {{Sex differences in off-target binding using tau positron emission tomography}},
  url          = {{http://dx.doi.org/10.1016/j.nicl.2021.102708}},
  doi          = {{10.1016/j.nicl.2021.102708}},
  volume       = {{31}},
  year         = {{2021}},
}