High-contrast in-vivo imaging of tau pathologies in Alzheimer’s and non-Alzheimer’s disease tauopathies

<jats:title>SUMMRAY</jats:title> <jats:p> A panel of radiochemicals has enabled <jats:italic>in-vivo</jats:italic> positron emission tomography (PET) of tau pathologies in Alzheimer’s disease (AD), while 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. <jats:italic>In-vitro</jats:italic> 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 <jats:sup>18</jats:sup> F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant PSP tau topologies. Notably, the <jats:italic>in-vivo</jats:italic> reactivity of <jats:sup>18</jats:sup> F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of autopsied and biopsied brains derived from Pick’s disease, PSP and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of <jats:sup>18</jats:sup> F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on the neuropathological basis. </jats:p>