Frontotemporal dementia (FTD) is in the majority of cases neuropathologically characterized by accumulation of either tau or TDP-43. PET tracers targeted at the protein tau could thus potentially predict underlying protein pathology. We examined the PET tracer [18F]RO948 retention in FTD, aiming to include cases with predictable underlying protein pathology.
We included 35 patients with FTD: 21 behavioural variant FTD (bvFTD) cases, 11 symptomatic C9orf72 mutations carriers, one patient with non-genetic bvFTD-amyotrophic lateral sclerosis (ALS), one individual with bvFTD due to a GRN mutation and one individual due to a MAPT mutation (R406W). All underwent [18F]RO948 PET and MRI. Two patients also underwent postmortem neuropathological examination. PET tracer retention was examined using a region-of-interest (ROI) and voxel-wise approaches. Comparison subjects were cases of Alzheimer´s disease (AD, n =13) and Aβ-negative cognitively unimpaired individuals (n =13). Tracer binding was also assessed using [3H]RO948autoradiography in six cases not from the present cohort.
[18F]RO948 retention across ROIs was comparable to that in Aβ-negative cognitively unimpaired individuals and clearly lower than in AD. Only minor loci of tracer retention were seen in FTD. Autoradiography did not show any [3H]RO948 binding. AD-like retention levels and specific in-vitro binding was however seen in the R406W MAPT mutation carriers.
[18F]RO948 uptake is not significantly increased in FTD patients and thus cannot predict underlying protein pathology in the majority of cases, with the clear exception being R406W MAPT mutation carriers. [18F]RO948 has however a promising specificity in differentiating AD from FTD.