In vivo distribution pattern of 18F-PM-PBB3 (18F-APN-1607) and its relationship with clinical featuresin diverse 4-repeat tauopathies

Objectives: Our previous examinations demonstrated that PET with 18F-PM-PBB3 (18F-APN-1607) shows a characteristic distribution pattern in patients with 4-repeat tauopathies such as progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), which is distinct from that observed in Alzheimer’s disease (AD). The present study aimed to investigate the association between 18F-PM-PBB3 uptake and clinical features in patients with clinically diagnosed 4-repeat tauopathies.Methods: 19 patients with 4-repeat tauopathies, including PSP with Richardson syndrome (PSP-RS), PSP with progressive gait freezing (PSP-PGF), PSP with predominant parkinsonism (PSP-P), PSP with predominant frontal presentation (PSP-F), PSP with ocular motor dysfunction (PSP-OM), PSP with predominant cerebellar ataxia (PSP-C), CBS-progressive non-fluent aphasia (CBS-PNFA), and biopsy-confirmed corticobasal degeneration (CBD) were recruited. Seven AD spectrum patients and 29 cognitively healthy controls (HCs) were also enrolled. All participants underwent PET scans with 18F-PM-PBB3 and 11C-PiB for estimating regional tau and Aβ deposition. Parametric 18F-PM-PBB3- and 11C-PiB- images were generated by voxel-based calculation of the standardized uptake value ratio (SUVR) to the cerebellar cortex.Results: PiB-negative patients with 4-repeat tauopathies showed remarkable uptake of PM-PBB3 especially around subthalamic nucleus, basal ganglia, midbrain including nigra and red nucleus, and dentate nucleus. Compared with PSP-RS, patients with PSP-OM, PSP-PGF and CBS/CBD showed relatively milder PM-PBB3 uptake especially around the midbrain. In contrast, patients with 4-repeat tauopathies having verbal and/or behavioral symptoms also presented elevated PM-PBB3 uptake in some cortices as well as the above-mentioned regions. Patients with 4-repeat tauopathies were easily differentiated from AD spectrum patients as well as HCs both by visual assessment and quantitative comparison of SUVR values in certain brain regions.Conclusions: Accumulations of PM-PBB3 may reflect characteristic distributions of tau pathologies in 4-repeat tauopathies, in conjunction with clinical manifestations. The present study provides further evidence for the potential utility of 18F-PM-PBB3 PET in tracking 4-repeat tau pathologies.Huma Amyloid Imaging Conference 201