Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation

Abstract

Background: Flortaucipir (AV-1451) and pyridinyl-butadienyl-benzothiazole 3 (PBB3) are newly developed and commonly used positron emission tomography (PET) tracers to detect tau deposition in tauopathies, including frontotemporal dementia (FTD). [18F]PM-PBB3, as a second-generation compound, has not been described in FTD so far.

Objective: We aim to explore the in vivo performance of [18F]PM-PBB3 tau PET in an FTD case caused by microtubule-associated protein tau (MAPT) mutation and compare the binding to different tau strains between AV-1451 and PBB3.

Methods: We reported the clinical and FDG, [18F]AV45 amyloid and [18F]PM-PBB3 tau PET findings in a patient with FTD of P301L MAPT mutation. Based on our results and published data, we summarized and compared the different utilities of tau PET tracers of AV-1451 and PBB3 in FTD with MAPT mutation.

Results: The patient demonstrated slightly diffuse [18F]PM-PBB3 tau deposition in cerebral lobes especially in the left frontal lobe overlapping with the hypometabolic region detected by FDG PET. From our analysis of 35 FTD patients with MAPT mutation who underwent tau PET, AV-1451 was positive in all (n = 11) patients with mutations known to cause three and four repeat (3R/4R) tau deposition and in 14.3% (n = 2/14) of 4R tauopathies, while positive PBB3 retention was found in all patients with both 3R/4R (n = 2) and 4R (n = 8) tau.

Conclusions: [18F]PM-PBB3 tau PET assisted the diagnosis of FTD with P301L MAPT mutation, and might be useful in the in vivo detection of both 3R/4R and 4R tau domains in the brain of FTD with MAPT mutation.

Keywords: AV-1451; MAPT mutation; [18F]PM-PBB3; frontotemporal dementia; positron emission tomography.