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[18F]RO948 tau positron emission tomography in genetic and sporadic frontotemporal dementia syndromes

Santillo, Alexander F. LU orcid ; Leuzy, Antoine LU ; Honer, Michael ; Landqvist Waldö, Maria LU ; Tideman, Pontus LU ; Harper, Luke LU ; Ohlsson, Tomas ; Moes, Svenja ; Giannini, Lucia and Jögi, Jonas LU orcid , et al. (2023) In European Journal of Nuclear Medicine and Molecular Imaging 50(5). p.1371-1383
Abstract

Purpose: To examine [18F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. Methods: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aβ-negative cognitively unimpaired individuals (n = 13) underwent [18F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed... (More)

Purpose: To examine [18F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. Methods: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aβ-negative cognitively unimpaired individuals (n = 13) underwent [18F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed in vitro using [3H]RO948 autoradiography in six separate cases. Results: [18F]RO948 retention across ROIs was clearly lower than in AD and comparable to that in Aβ-negative cognitively unimpaired individuals. Only minor loci of tracer retention were seen in bvFTD; these did not overlap with the observed cortical atrophy in the cases, the expected pattern of atrophy, nor the expected or verified protein pathology distribution. Autoradiography analyses showed no specific [3H]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding. Conclusion: [18F]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C9orf72, Frontotemporal dementia, FTD, MAPT, PET, Progranulin, Tau, [F]RO948
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
50
issue
5
pages
1371 - 1383
publisher
Springer
external identifiers
  • scopus:85143887800
  • pmid:36513817
ISSN
1619-7070
DOI
10.1007/s00259-022-06065-4
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022, The Author(s).
id
a35a4519-76b9-4cc1-bc94-109586bad02e
date added to LUP
2022-12-23 08:15:18
date last changed
2024-06-26 00:18:27
@article{a35a4519-76b9-4cc1-bc94-109586bad02e,
  abstract     = {{<p>Purpose: To examine [<sup>18</sup>F]RO948 retention in FTD, sampling the underlying protein pathology heterogeneity. Methods: A total of 61 individuals with FTD (n = 35), matched cases of AD (n = 13) and Aβ-negative cognitively unimpaired individuals (n = 13) underwent [<sup>18</sup>F]RO948PET and MRI. FTD included 21 behavioral variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutation carriers, one patient with non-genetic bvFTD-ALS, one individual with bvFTD due to a GRN mutation, and one due to a MAPT mutation (R406W). Tracer retention was examined using a region-of-interest and voxel-wise approaches. Two individuals (bvFTD due to C9orf72) underwent postmortem neuropathological examination. Tracer binding was additionally assessed in vitro using [<sup>3</sup>H]RO948 autoradiography in six separate cases. Results: [<sup>18</sup>F]RO948 retention across ROIs was clearly lower than in AD and comparable to that in Aβ-negative cognitively unimpaired individuals. Only minor loci of tracer retention were seen in bvFTD; these did not overlap with the observed cortical atrophy in the cases, the expected pattern of atrophy, nor the expected or verified protein pathology distribution. Autoradiography analyses showed no specific [<sup>3</sup>H]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding. Conclusion: [<sup>18</sup>F]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.</p>}},
  author       = {{Santillo, Alexander F. and Leuzy, Antoine and Honer, Michael and Landqvist Waldö, Maria and Tideman, Pontus and Harper, Luke and Ohlsson, Tomas and Moes, Svenja and Giannini, Lucia and Jögi, Jonas and Groot, Colin and Ossenkoppele, Rik and Strandberg, Olof and van Swieten, John and Smith, Ruben and Hansson, Oskar}},
  issn         = {{1619-7070}},
  keywords     = {{C9orf72; Frontotemporal dementia; FTD; MAPT; PET; Progranulin; Tau; [F]RO948}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1371--1383}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{[<sup>18</sup>F]RO948 tau positron emission tomography in genetic and sporadic frontotemporal dementia syndromes}},
  url          = {{http://dx.doi.org/10.1007/s00259-022-06065-4}},
  doi          = {{10.1007/s00259-022-06065-4}},
  volume       = {{50}},
  year         = {{2023}},
}