18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies

Abstract

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters.Methods:18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke’s Cognitive Examination–Revised, and Frontal Assessment Battery, Unified Parkinson’s Disease Rating Scale Motor Score, and PSP Rating Scale.Results:18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP.Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.

Neuropathology and emerging biomarkers in corticobasal syndrome

“… 152 The THK-5351 retention pattern was different among AD, PSP and CBS, but none of the patients had autopsy confirmation. 153 The underlying pathology of CBS patients remained unclear; therefore, the usefulness of THK-5351 in differentiating the pathology of CBS, particularly CBD or PSP, needs to be elucidated.…”

Imaging of Reactive Astrogliosis by Positron Emission Tomography

“…Although there were a lot of limitations to interpret [ 18 F]THK-5351 PET images on the biological point of view due to the lack of selectivity, many clinical studies using [ 18 F]THK-5351 imply the association of reactive astrogliosis in various conditions. Clinical PET studies demonstrated high and different distribution of [ 18 F]THK-5351 retention in sites susceptible to tau deposition in AD and non-AD conditions such as Parkinsonian syndromes ( Harada et al, 2016 ; Kikuchi et al, 2016 ; Brendel et al, 2017 ; Ishiki et al, 2017 ; Shimizu et al, 2018 ; Schonecker et al, 2019 ; Hsu et al, 2020 ; Ezura et al, 2021 ; Figure 2 ). Furthermore, [ 18 F]THK-5351 retention mirrors glucose hypometabolism measured with [ 18 F]fluorodeoxyglucose in the focal variants of AD ( Kang et al, 2017 ; Park et al, 2021 ).…”

Amyloid and Tau Positron Emission Tomography Imaging in Alzheimer’s Disease and Other Tauopathies

“…Nihashi et al (2021) suggested that the quantity of [ 18 F]THK5351 uptake in the brain of AD patients inversely correlated with hippocampal volume and neuropsychological assessment, implying that [ 18 F]THK5351 may be a candidate for monitoring AD disease progression. Ezura et al (2021) compared differential binding of [ 18 F]THK5351 to different tauopathies and found that high [ 18 F]THK5351 uptake was detected in the precentral and postcentral gyri of CBD patients, in the midbrain of PSP patients and in the parahippocampal gyri of AD patients compared to healthy controls, clearly distinguishing different tauopathies. In vivo imaging using [ 11 C]PBB3 showed the detection of tau inclusions in the brain stem of PS19 and cortical and hippocampal regions of the rTg4510 mouse model of FTD (Maruyama et al, 2013;Ishikawa et al, 2018;Ni et al, 2018;Vagenknecht et al, 2022).…”