Abstract
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Objectives The pathophysiology of progressive supranuclear palsy (PSP) is characterized by deposition of fibrillar aggregates of 4-repeat tau protein in neurons. These deposits are a key finding leading to the neuropathological diagnosis of “definite PSP”, which is usually established post mortem. The diagnosis of PSP in vivo according to current criteria does not take tau pathology into consideration. In light of future intervention trials biomarkers to establish a molecular diagnosis and also as potential markers of disease progression become increasingly important. [18F]THK-5351 as a novel Tau-PET ligand may allow in vivo visualization and quantification of tau deposits, therefore the aim of the study is to investigate characteristics of [18F]THK-5351 binding in patients with clinically diagnosed PSP and correlate tau-tracer uptake with clinical findings.
Methods Six patients with probable PSP according to current criteria underwent [18F]THK-5351 PET scanning. PET scans were acquired 40-60 min p. i. and were coregistered to the individual MRI. Standardized uptake value ratio (SUVR) in predefined brain regions were generated using the cerebellar cortex as reference region. Additionally disease severity measured by the PSP Rating Scale (PSPRS), functional independence measured by Schwab and England Activities of Daily Living scale (SEADL) and disease duration were assessed and correlated with PET findings.
Results In 5/6 patients significantly increased [18F]THK-5351 binding was found predominantly in midbrain (SUVR 2.8-3.9), compared to a historical subject with AD (SUVR 2.2). Uptake correlated with clinical severity defined by PSPRS. One subject with a PSPRS of 33/100 and additional innate hydrocephalus did not show an elevated midbrain uptake (SUVR 2.1), suggesting no underlying tauopathy responsible for the clinical presentation.
Conclusions [18F]THK-5351 binding patterns correlated well with the known distribution of tau-pathology at autopsy in PSP and clinical severity. [18F]THK-5351 seems to be a useful biomarker of tau deposition and may therefore facilitate earlier and more reliable diagnosis of PSP.