High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies

Highlights

• •A new probe, PM-PBB3, captures pathological tau deposits in vivo with high contrast
• •PM-PBB3 allows an individual-based identification of AD and non-AD tauopathies
• •Autopsy assays of PET-scanned patients supported the in vivo performance of PM-PBB3

Summary

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer’s disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of ¹⁸F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of ¹⁸F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick’s disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of ¹⁸F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.