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

Purpose To examine [F-18]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 A beta-negative cognitively unimpaired individuals (n = 13) underwent [F-18]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 [H-3]RO948 autoradiography in six separate cases.Results [F-18]RO948 retention across ROIs was clearly lower than in AD and comparable to that in A beta-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 [H-3]RO948 binding. The R406W MAPT mutation carriers were clear exceptions with AD-like retention levels and specific in-vitro binding.Conclusion [F-18]RO948 uptake is not significantly increased in the majority of FTD patients, with a clear exception being specific MAPT mutations.

Automated summary

The uptake of [F-18]RO948 is not significantly increased in the majority of FTD patients, with the exception of specific MAPT mutations. The observed tracer retention does not overlap with the cortical atrophy, expected pattern of atrophy, or verified protein pathology distribution.