Objective: The objective of our study is to investigate characteristics of THK-5351 binding in patients with clinically diagnosed progressive supranuclear palsy (PSP) and correlate tau-tracer uptake with clinical findings.

Background: The pathophysiology of 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. THK-5351 is a novel Tau-PET ligand that may allow in vivo visualization and quantification of tau deposits.

Methods: 6 Patients with probable PSP according to current criteria received THK-5351 PET scanning. PET scans were acquired 40-60 min post injection and were co-registered to MRI. A visual as well as a semi-quantitative analysis of tracer binding (standardized uptake value ratio) in predefined cortical areas was performed using the cerebellar cortex as reference region. Additionally disease severity measured by the PSP Rating Scale, functional independence measured by Schwab and England Activities of Daily Living scale (SEADL) and disease duration were assessed.

Results: Increased THK-5351 binding was detectable in striatum, thalamus and brainstem, especially in the midbrain. 5/6 subjects indicated clearly elevated THK-5351 uptake in the midbrain (SUVR: 2.8 – 3.9) compared to non-suspect PSP (SUVR: 2.2). One subject suspect to PSP with innate hydrocephalus, did not show an elevated THK-5351 midbrain signal (SUVR: 2.1), suggesting no underlying tauopathy in this case.

Conclusions: THK-5351 binding patterns correlated well with the known distribution of tau-pathology at autopsy in PSP. THK-5351 seems to be a useful biomarker of tau deposition and may therefore facilitate earlier and more reliable diagnosis of PSP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/thk-5351-tau-tracer-uptake-in-patients-with-clinically-diagnosed-progressive-supranuclear-palsy/