Neuroimaging-pathological correlations of [18F]THK5351 PET in progressive supranuclear palsy

Aiko Ishiki,Naoki Tomita,Naomi Sato,Hironobu Sasano,Hideaki Kai,Shozo Furumoto,Ren Iwata,Tetsuyuki Kitamoto,Ryuichi Harada,Masato Tashiro ,Koichi Furukawa ,Yoshihisa Kudo ,S Watanuki ,Y Funaki ,Tomoko Totsune,Kazuhiko Yanai,Yoichi Ishikawa,Nobuyuki Okamura,Kotaro Hiraoka,Hiroyuki Arai

doi:10.1186/s40478-018-0556-7

Abstract

Recent positron emission tomography (PET) studies have demonstrated the accumulation of tau PET tracer in the affected region of progressive supranuclear palsy (PSP) cases. To confirm the binding target of radiotracer in PSP, we performed an imaging-pathology correlation study in two autopsy-confirmed PSP patients who underwent [18F]THK5351 PET before death. One patient with PSP Richardson syndrome showed elevated tracer retention in the globus pallidus and midbrain. In a patient with PSP-progressive nonfluent aphasia, [18F]THK5351 retention also was observed in the cortical areas, particularly the temporal cortex. Neuropathological examination confirmed PSP in both patients. Regional [18F]THK5351 standardized uptake value ratio (SUVR) in antemortem PET was significantly correlated with monoamine oxidase-B (MAO-B) level, reactive astrocytes density, and tau pathology at postmortem examination. In in vitro autoradiography, specific THK5351 binding was detected in the area of antemortem [18F]THK5351 retention, and binding was blocked completely by a reversible selective MAO-B inhibitor, lazabemide, in brain samples from these patients. In conclusion, [18F]THK5351 PET signals reflect MAO-B expressing reactive astrocytes, which may be associated with tau accumulation in PSP.

Highlights

Tau positron emission tomography (PET), which provides the topographic distribution of tau aggregates in the brain, would be useful for the diagnosis of Alzheimer’s disease (AD) and for the assessment of tau burden in the clinical trials of antidementia drugs
[18F]THK5351 PET signal reflects the combination of tau pathology and reactive astrocytes in the AD brain [10]
We examined imaging-pathology correlation in two autopsy-confirmed progressive supranuclear palsy (PSP) patients who showed prominent tracer retention on an antemortem [18F]THK5351 PET scan

Summary

Introduction

Tau positron emission tomography (PET), which provides the topographic distribution of tau aggregates in the brain, would be useful for the diagnosis of Alzheimer’s disease (AD) and for the assessment of tau burden in the clinical trials of antidementia drugs. Clinical PET studies in PSP and CBS patients have demonstrated prominent [18F]THK5351 retention [2, 14, 19] in the midbrain and basal ganglia where tau pathology was observed frequently at autopsy [20, 45]. [18F]THK5351 binding in these areas is associated closely with disease progression because the amount of tracer retention was correlated positively with clinical severity of PSP [2]. A single oral dose of selegiline, a selective irreversible MAO-B inhibitor, substantially reduced [18F]THK5351 binding in the brain of patients with PSP as well as AD [29]. In an autopsy case of AD, regional [18F]THK5351 binding was correlated significantly with MAO-B density as well as tau level. What an [18F]THK5351 PET signal reflects in the PSP brain remains unclear

Methods

Results

Discussion

Conclusion