TY - JOUR T1 - In vivo <sup>18</sup>F-flortaucipir PET does not accurately support the staging of progressive supranuclear palsy JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.262985 SP - jnumed.121.262985 AU - Maura Malpetti AU - Sanne S Kaalund AU - Kamen A Tsvetanov AU - Timothy Rittman AU - Mayen Briggs AU - Kieren Allinson AU - Luca Passamonti AU - Negin Holland AU - P Simon Jones AU - Tim D Fryer AU - Young T Hong AU - Antonina Kouli AU - Richard Bevan-Jones AU - Elijah Mak AU - George Savulich AU - Maria Grazia Spillantini AU - Franklin Aigbirhio AU - Caroline H Williams-Gray AU - John T O'Brien AU - James B Rowe Y1 - 2021/11/01 UR - http://jnm.snmjournals.org/content/early/2021/11/18/jnumed.121.262985.abstract N2 - Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by neuro-glial tau pathology. A new staging system for PSP pathology at post-mortem has been described and validated. We used a data-driven approach to test whether post-mortem pathological staging in PSP can be reproduced in vivo with 18F-flortaucipir PET. Methods: N = 42 patients with probable PSP and N = 39 controls underwent 18F-flortaucipir PET. Conditional inference tree analyses on regional binding potential values identified absent/present pathology thresholds to define in vivo staging. Following the staging system for PSP pathology, the combination of absent/present values across all regions was evaluated to assign each participant to in vivo stages. Analysis of variance was applied to analyse differences among means of disease severity between stages. In vivo staging was compared with post-mortem staging in N = 9 patients who also had post-mortem confirmation of the diagnosis and stage. Results: Stage assignment was estimable in 41 patients: N = 10 patients were classified in stage I/II, N = 26 in stage III/IV, N = 5 in stage V/VI, while N = 1 was not classifiable. An explorative sub-staging identified N = 2 patients in stage I, N = 8 in stage II, N = 9 in stage III, N = 17 in stage IV and N = 5 in stage V. However, the nominal 18F-flortaucipir derived stage was not associated with clinical severity and was not indicative of pathology staging at post-mortem. Conclusion: 18F-flortaucipir PET in vivo does not correspond to neuropathological staging in PSP. This analytic approach, seeking to mirror in vivo the neuropathology staging with PET-to-autopsy correlational analyses might enable in vivo staging with next-generation PET tracers for tau, but further evidence and comparison with post-mortem data are needed. ER -