To examine correlations between in vivo positron emission tomography (PET) imaging with 18F-PM-PBB3 (18F-florzolotau) and postmortem neuropathological findings in a patient with progressive supranuclear palsy (PSP).

There have been no reports demonstrating tight PET-pathology associations in the same individual with non-Alzheimer-type neurodegenerative disorders, including PSP, characterized by aggregations of four-repeat tau isoforms only. 18F-florzolotau is a PET probe allowing high-contrast imaging of Alzheimer’s and non-Alzheimer tau pathologies irrespective of isoform compositions, while the utility of this tracer for quantifying the abundance of tau deposits in living cases is yet to be verified.

Patient

A 65-year-old male with a clinical diagnosis of PSP Richardson syndrome underwent 11C-PiB amyloid and 18F-florzolotau tau PET scans one year before autopsy. Clinical, neuroimaging, and neuropathological findings in this case were briefly summarized elsewhere (K Tagai, et al. Neuron 2021).

Image analysis

The standardized uptake value ratio (SUVR) image was generated from averaged PET images at 90–110 min after injecting 18F-florzolotau. The reference region was determined using an optimized reference tissue method (K Tagai, et al. medRxiv DOI: https://doi.org/10.1101/2022.02.13.22270135 ).

Neuropathological analysis

Quantitative analysis of tau burden was performed using an anti-phosphorylated tau antibody (AT8). A threshold-based binarization method was used for determining the mean AT-8-positive area (%area tau burden).

18F-florzolotau PET showed enhanced radiosignals in the brainstem, subthalamic nucleus, and basal ganglia, and the presence of PSP-characteristic tau deposits, including the globose neurofibrillary tangle, tufted astrocytes and coiled bodies, primarily in these areas was confirmed by neuropathological assays. There was a close correlation between regional radioprobe SUVR and %area tau burden (r_s = 0.63, p <0.0001). Amyloid PET was negative by visual read.

18F-florzolotau PET measures reflect the abundance of tau pathologies in PSP.