A head-to-head comparison between [11C]PBB3 and [18F]PM-PBB3 in patients with AD and non-AD tauopathy

Background:We recently developed a novel fluorinated tau PET ligand, [18F]PM-PBB3, to improve characteristics of [11C]PBB3. Our preclinical evidence suggested that [18F]PM-PBB3 could capture tau deposits in living brains with high contrast and favorable kinetics. Here, we conducted a head-to-head comparison between PET data obtained using [11C]PBB3 and [18F]PM-PBB3 in patients with Alzheimer’s disease (AD) and non-AD tauopathy.Methods:Patients with AD and progressive supranuclear palsy (PSP), and healthy controls (HCs) underwent three PET scans with [11C]PiB, [11C]PBB3, and [18F]PM-PBB3. In the scan with [18F]PM-PBB3, arterial blood sampling was performed to determine binding potential (BPND) of the radioligand based on a compartment model. We also calculated BPND by a reference tissue model and standardized uptake value ratio (SUVR) using the cerebellum gray matter as reference. These estimates were compared to SUVR values of [11C]PBB3 in each subject.Results:The BPND values of [18F]PM-PBB3 by a reference tissue model and SUVR were in good agreement with those by a compartment model. Compared to [11C]PBB3, the peak brain radioactivity and contrast for tau lesions yielded by [18F]PM-PBB3 were almost double of those produced by [11C]PBB3. Unlike [11C]PBB3, [18F]PM-PBB3 showed minimal off-site binding in the brain parenchyma including the striatum. Binding of [18F]PM-PBB3 in the brainstem was not evident in AD patients and HCs, but was prominent in PSP patients, resulting in a vivid contrast between PSP patients and the other subjects.Conclusion:The current results indicate that [18F]PM-PBB3 would be a promising PET ligand to quantify tau accumulation in AD and PSP patients with suitable kinetics and high contrast. The wide dynamic range and minimal parenchymal off-site binding of [18F]PM-PBB3 would allow its application to differentiations among AD, non-AD tauopathies and HC by both visual inspection and quantitative assessments on an individual basis in a clinical workup.12th Human Amyloid Imagin