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

Alexander F. Santillo, Antoine Leuzy, Michael Honer, Maria Landqvist Waldö, Pontus Tideman, Luke Harper, Tomas Ohlsson, Svenja Moes, Lucia Giannini, Jonas Jögi, Colin Groot, Rik Ossenkoppele, Olof Strandberg, John van Swieten, Ruben Smith, Oskar Hansson

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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 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.
Original languageEnglish
JournalEuropean journal of nuclear medicine and molecular imaging
Early online date2022
DOIs
Publication statusE-pub ahead of print - 2022

Keywords

  • C9orf72
  • FTD
  • Frontotemporal dementia
  • MAPT
  • PET
  • Progranulin
  • Tau
  • [ F]RO948

Cite this