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Background: Alzheimer's disease (AD) is conceptualized as a biological continuum encompassing the preclinical (clinically asymptomatic but with evidence of AD pathology) and clinical (symptomatic) phases., Objective: Using 18F-THK5351 as a tracer that binds to both tau and monoamine oxidase B (MAO-B), we investigated the changes in 18F-THK5351 accumulation patterns in AD continuum individuals with positive amyloid PET consisting of cognitively normal individuals (CNp), amnestic mild cognitive impairment (aMCI), and AD and cognitively normal individuals (CNn) with negative amyloid PET., Methods: We studied 69 individuals (32 CNn, 11 CNp, 9 aMCI, and 17 AD) with structural magnetic resonance imaging, 11C-Pittsburgh compound-B (PIB) and 18F-THK5351 PET, and neuropsychological assessment. 18F-THK5351 accumulation was evaluated with visual analysis, voxel-based analysis and combined region of interest (ROI)-based analysis corresponding to Braak neurofibrillary tangle stage., Results: On visual analysis, 18F-THK5351 accumulation was increased with stage progression in the AD continuum. On voxel-based analysis, there was no statistical difference in 18F-THK5351 accumulation between CNp and CNn. However, a slight increase of the bilateral posterior cingulate gyrus in aMCI and definite increase of the bilateral parietal temporal association area and posterior cingulate gyrus/precuneus in AD were detected compared with CNn. On ROI-based analyses, 18F-THK5351 accumulation correlated positively with supratentorial 11C-PIB accumulation and negatively with the hippocampal volume and neuropsychological assessment., Conclusion: The AD continuum showed an increase in 18F-THK5351 with stage progression, suggesting that 18F-THK5351 has the potential to visualize the severity of tau deposition and neurodegeneration in accordance with the AD continuum.

Clinical PET studies using 18 F-THK5351 have demonstrated significant tracer retention in sites susceptible to tau burden in Alzheimer disease (AD). However, the in vivo PET signal to reflect tau aggregates remains controversial. Methods: We examined the spatial pattern of tracer binding, amyloid-β, tau, and gliosis in an autopsy-confirmed AD patient who underwent 18 F-THK5351 and 11 C-Pittsburgh compound B PET before death. Results: Regional in vivo 18 F-THK5351 retention was significantly correlated with the density of tau aggregates in the neocortex and monoamine oxidase-B in the whole brain, but not correlated with that of insoluble amyloid-β. Furthermore, significant association was observed between the density of tau aggregates, monoamine oxidase-B, and glial fibrillary acidic protein, suggesting that neocortical tau would strongly influence the formation of reactive astrocytes. Conclusion: 18 F-THK5351 PET may have limited utility as a biomarker of tau pathology in AD; however, it could be used to monitor the neuroinflammatory processes in the living brain., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

This study aims to evaluate the clinical validity of [ 18 F]THK5351 positron emission tomography (PET) for the assessment of disease progression and symptoms in Alzheimer's disease (AD). Fifty-one patients with AD dementia, 30 patients with amnestic mild cognitive impairment (aMCI), and 43 controls with normal cognition (NC) were included. All subjects underwent [ 18 F]THK5351 PET, 3.0-T magnetic resonance imaging, and detailed neuropsychological tests. Regions of interest and voxel-based statistical analyses were performed. In patients with AD dementia, [ 18 F]THK5351 retention was greater in most association cortices as well as the limbic area compared to NC or aMCI participants. Patients with aMCI also showed higher THK5351 retention in those areas compared to NC. [ 18 F]THK5351 retention significantly correlated with neuropsychological test results. Negative correlations between [ 18 F]THK5351 and [ 18 F] fluorodeoxyglucose were observed in AD dementia and aMCI groups. Mirror images of [ 18 F]THK5351 retention and glucose hypometabolism in [ 18 F] fluorodeoxyglucose were noticeable in the focal variants of AD. [ 18 F]THK5351 PET reflects disease severity and symptoms in AD. Our results suggest [ 18 F]THK5351 is reflective of tau-related AD pathology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study., Methods: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [ 18 F]THK5351 and [ 11 C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data., Results: In regions of high uptake of [ 18 F]THK5351 and [ 11 C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition., Conclusion: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

Background and Purpose: Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy (PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [ 18 F]THK-5351, which we have recently developed., Methods: Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [ 3 H]THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [ 18 F]THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed., Results: Autoradiography in the brain sections of patients with PSP demonstrated [ 3 H]THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [ 18 F]THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP., Conclusions: We conclude that [ 18 F]THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein., (© 2016 EAN.)

Objective: To determine whether 18 F-THK5351 PET can be used to visualize tau deposits in brain lesions in live patients with corticobasal syndrome (CBS)., Methods: We evaluated the in vitro binding of 3 H-THK5351 in postmortem brain tissues from a patient with corticobasal degeneration (CBD). In clinical PET studies, 18 F-THK5351 retention in 5 patients with CBS was compared to that in 8 age-matched normal controls and 8 patients with Alzheimer disease (AD)., Results: 3 H-THK5351 was able to bind to tau deposits in the postmortem brain with CBD. In clinical PET studies, the 5 patients with CBS showed significantly higher 18 F-THK5351 retention in the frontal, parietal, and globus pallidus than the 8 age-matched normal controls and patients with AD. Higher 18 F-THK5351 retention was observed contralaterally to the side associated with greater cortical dysfunction and parkinsonism., Conclusions: 18 F-THK5351 PET demonstrated high tracer signal in sites susceptible to tau deposition in patients with CBS. 18 F-THK5351 should be considered as a promising candidate radiotracer for the in vivo imaging of tau deposits in CBS., (© 2016 American Academy of Neurology.)

Purpose: 18 F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of 18 F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties., Methods: Venous blood samples were collected from three human subjects after injection of 18 F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples., Results: About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of 18 F-THK5351. The isolated radiometabolite of 18 F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples., Conclusions: These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images.

Alzheimer's disease and other neurodegenerative dementias belong to the family of tauopathies. These diseases are characterized by the deposition of insoluble tau aggregates possessing an enriched β-sheet structure. In vivo imaging of the tau deposits by positron emission tomography (PET) will facilitate the early and accurate diagnosis of these diseases, tracking of disease progression, assessment of disease severity, and prediction of disease prognosis. Furthermore, this technology is expected to play a vital role in the monitoring of treatment outcomes and in the selection of patients for the therapeutic trials of anti-dementia drugs. Recently, several tau PET tracers have been successfully developed and demonstrated as having high binding affinity and selectivity to tau protein deposits. Recent clinical studies using these tracers have demonstrated significant tracer retention in sites susceptible to tau deposition in Alzheimer's disease, as well as correlations with the disease severity and cognitive impairment in cases with dementia. These tracers, thus, have the potential to effectively diagnose the tauopathies. Further longitudinal assessment will clarify the effect of the tau deposition on the neurodegenerative process and cognitive decline and the interaction of tau with amyloid-β in the human brain., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: [18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images., Methods: Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR., Results: In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences., Conclusions: We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.

Purpose: Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [(18)F]THK-5105 enantiomers., Procedures: Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay, Results: The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[(18)F]THK-5105., Conclusion: (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

Tau deposition is one of the neuropathological hallmarks in Alzheimer's disease as well as in other neurodegenerative disorders called tauopathies. Recent efforts to develop selective tau radiopharmaceuticals have allowed the visualization of tau deposits in vivo. In vivo tau imaging allows the assessment of the regional distribution of tau deposits in a single human subject over time for determining the pathophysiology of tau accumulation in aging and neurodegenerative conditions as well as for application in drug discovery of anti-dementia drugs as surrogate markers. However, tau deposits show complicated characteristics because of different isoform composition, histopathology, and ultrastructure in various neurodegenerative conditions. In addition, since tau radiopharmaceuticals possess different chemotype classes, they may show different binding characteristics with heterogeneous tau deposits. In this review, we describe the characteristics of tau deposits and their ligands that have β-sheet binding properties, and the status of tau imaging in clinical studies.

The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [18F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [18F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [18F]THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.

In several neurodegenerative diseases that are collectively called tauopathies, progressive accumulation of tau in the brain is closely associated with neurodegeneration and cognitive impairment. Noninvasive detection of tau protein deposits in the brain would be useful to diagnose tauopathies as well as to track and predict disease progression. Recently, several tau PET tracers including T807, THK-5117, and PBB3 have been developed and succeeded in imaging neurofibrillary pathology in vivo. For use of tau PET as a biomarker of tau pathology in Alzheimer's disease, PET tracers should have high affinity to PHF-tau and high selectivity for tau over amyloid-β and other protein deposits. PET tau imaging enables the longitudinal assessment of the spatial pattern of tau deposition and its relation to amyloid-β pathology and neurodegeneration. This technology could also be applied to the pharmacological assessment of anti-tau therapy, thereby allowing preventive interventions.

Purpose: Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate (18)F-THK523 as a potential tau imaging tracer., Methods: Ten healthy elderly controls, three semantic dementia (SD) and ten AD patients underwent neuropsychological examination, MRI as well as (18)F-THK523 and (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET) scans. Composite memory and non-memory scores, global and hippocampal brain volume, and partial volume-corrected tissue ratios for (18)F-THK523 and (11)C-PIB were estimated for all participants. Correlational analyses were performed between global and regional (18)F-THK523, (11)C-PIB, cognition and brain volumetrics., Results: (18)F-THK523 presented with fast reversible kinetics. Significantly higher (18)F-THK523 retention was observed in the temporal, parietal, orbitofrontal and hippocampi of AD patients when compared to healthy controls and SD patients. White matter retention was significantly higher than grey matter retention in all participants. The pattern of cortical (18)F-THK523 retention did not correlate with Aβ distribution as assessed by (11)C-PIB and followed the known distribution of tau in the AD brain, being higher in temporal and parietal areas than in the frontal region. Unlike (11)C-PIB, hippocampal (18)F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy., Conclusion: (18)F-THK523 does not bind to Aβ in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain. Significantly higher cortical (18)F-THK523 retention in AD patients as well as the association of hippocampal (18)F-THK523 retention with cognitive parameters and hippocampal volume suggests (18)F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high (18)F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.

Purpose: Selective visualization of amyloid-β and tau protein deposits will help to understand the pathophysiology of Alzheimer's disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique., Procedures: Fluorescence spectral analysis was performed using AD brain sections stained with novel fluorescence compounds. Competitive binding assay using [(3)H]-PiB was performed to evaluate the binding affinity of BF-188 for synthetic amyloid-β (Aβ) and tau fibrils., Results: In AD brain sections, BF-188 clearly stained Aβ and tau protein deposits with different fluorescence spectra. In vitro binding assays indicated that BF-188 bound to both amyloid-β and tau fibrils with high affinity (K i  < 10 nM). In addition, BF-188 showed an excellent blood-brain barrier permeability in mice., Conclusion: Multispectral imaging with BF-188 could potentially be used for selective in vivo imaging of tau deposits as well as amyloid-β in the brain.

Alzheimer's disease (AD) is the most common cause of dementia. Senile plaques, consisting of β-amyloid, and neurofibrillary tangles (NFTs), composed of tau protein, are representative pathological hallmarks of AD. It is believed that the accumulation of NFTs precedes the onset of clinical symptoms of AD and correlates with the progression of memory dysfunction. Thus, the use of noninvasive detection techniques including radiolabeled probes and positron emission tomography (PET) will facilitate early diagnosis or staging of AD. In this study, we synthesized and evaluated novel hydroxylated 2-arylquinoline derivatives as tau imaging PET probes. The binding affinities of compounds for tau were evaluated by fluorescent staining of the AD hippocampal section and a competitive binding assay using [(18) F]THK-523. THK-951 showed high binding affinity for tau pathology in an AD brain section and K18Δ280K fibrils (Ki  = 20.7 nM); thus, we radiosynthesized a (11) C-labeled THK-951 and further studied its potential as a tau PET probe. The [(11) C]THK-951 demonstrated excellent kinetics in a normal mouse brain (3.23% ID/g at 2 min postinjection and 0.15% ID/g at 30 min postinjection) and showed the labeling of NFTs in an AD brain section by autoradiography assay. These findings indicate the availability of [(11) C]THK-951 for in vivo PET imaging of tau pathology in AD., (Copyright © 2013 John Wiley & Sons, Ltd.)

Unlabelled: Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the microtubule-associated protein tau. Noninvasive monitoring of tau protein aggregates in the living brain will provide useful information regarding tau pathophysiology in AD. However, no PET probes are currently available for selective detection of tau pathology in AD. We have previously reported (18)F-labeled THK-523 ((18)F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau imaging radiotracer candidate for PET. After compound optimization, we developed novel (18)F-labeled arylquinoline derivatives, (18)F-THK-5105 and (18)F-THK-5117, for use as tau imaging PET tracers., Methods: (18)F-labeled compounds were prepared from the corresponding tosylated precursors. The binding affinity of compounds to synthetic tau aggregates and tau-rich AD brain homogenates was determined by saturation and competition binding assays. The binding selectivity of compounds to tau pathology was evaluated by autoradiography of AD brain sections. The pharmacokinetics of compounds were assessed in biodistribution studies in normal mice. A 14-d toxicity study with intravenous administration of compounds was performed using rats and mice., Results: In vitro binding assays demonstrated higher binding affinity of THK-5105 and THK-5117 than THK-523 to tau protein aggregates and tau-rich AD brain homogenates. Autoradiographic analyses of AD brain sections showed that these radiotracers preferentially bound to neurofibrillary tangles and neuropil threads, which colocalized with Gallyas-positive and immunoreactive tau protein deposits. The distribution of this radiotracer binding in AD brain sections was completely different from that of (11)C-Pittsburgh compound B, showing preferential binding to amyloid plaques. Furthermore, these derivatives demonstrated abundant initial brain uptake and faster clearance in normal mice than (18)F-THK-523 and other reported (18)F-labeled radiotracers. THK-5105 and THK-5117 showed no toxic effects related to the administration of these compounds in mice and rats and no significant binding for various neuroreceptors, ion channels, and transporters at 1-μM concentrations., Conclusion: (18)F-labeled THK-5105 and THK-5117 are promising candidates as PET tau imaging radiotracers.

While considerable effort has focused on developing positron emission tomography β-amyloid imaging radiotracers for the early diagnosis of Alzheimer's disease, no radiotracer is available for the non-invasive quantification of tau. In this study, we detail the characterization of (18)F-THK523 as a novel tau imaging radiotracer. In vitro binding studies demonstrated that (18)F-THK523 binds with higher affinity to a greater number of binding sites on recombinant tau (K18Δ280K) compared with β-amyloid(1-42) fibrils. Autoradiographic and histofluorescence analysis of human hippocampal serial sections with Alzheimer's disease exhibited positive THK523 binding that co-localized with immunoreactive tau pathology, but failed to highlight β-amyloid plaques. Micro-positron emission tomography analysis demonstrated significantly higher retention of (18)F-THK523 (48%; P < 0.007) in tau transgenic mice brains compared with their wild-type littermates or APP/PS1 mice. The preclinical examination of THK523 has demonstrated its high affinity and selectivity for tau pathology both in vitro and in vivo, indicating that (18)F-THK523 fulfils ligand criteria for human imaging trials.

Neurofibrillary tangles (NFTs), neuropil threads, and neuritic elements of senile plaques predominantly comprise hyperphosphorylated tau protein and represent pathological characteristics of Alzheimer's disease (AD). These lesions occur before the presentation of clinical symptoms and correlate with the severity of dementia. In vivo detection of these lesions would thus prove useful for preclinical diagnosis of AD and for tracking disease progression. The present study introduces three novel compounds, 4-[2-(2-benzoimidazolyl)ethenyl]-N,N-diethylbenzenamine (BF-126), 2-[(4-methylamino)phenyl]quinoline (BF-158), and 2-(4-aminophenyl)quinoline (BF-170), as candidate probes for in vivo imaging of tau pathology in the AD brain. When solutions of these compounds are injected intravenously into normal mice, these agents exhibit excellent brain uptake and rapid clearance from normal brain tissue. These compounds display relatively lower binding affinity to beta-amyloid fibrils and higher binding affinity to tau fibrils, compared with previously reported probe BF-168. In neuropathological examination using AD brain sections, BF-126, BF-158, and BF-170 clearly visualize NFTs, neuropil threads, and paired helical filament-type neuritis. Autoradiography using 11C-labeled BF-158 further demonstrated labeling of NFTs in AD brain sections. These findings suggest the potential usefulness of quinoline and benzimidazole derivatives for in vivo imaging of tau pathology in AD.

Background and purpose Visualization of pathogenic protein aggregates is crucial to elucidate pathomechanisms and to make an accurate diagnosis in many neurodegenerative conditions. Aggregates of the microtubule-binding protein, tau, are one of the most important pathogenic molecules in neurodegenerative disorders. Progressive supranuclear palsy ( PSP) is characterized by the deposition of tau proteins in some specific area such as the basal ganglia and brainstem. We tried to detect tau lesions in the brains of living patients with PSP with a novel positron emission tomography (PET) tracer, [18F] THK-5351, which we have recently developed. Methods Paraffin-embedded brain sections of the patients with PSP were used for autoradiography with [3H] THK-5351 and immunohistochemistry. Nine healthy controls, 13 patients with Alzheimer's disease and three patients with PSP participated in this PET study with [18F] THK-5351. To detect amyloid-β deposition, PET imaging with Pittsburgh compound B was also performed. Results Autoradiography in the brain sections of patients with PSP demonstrated [3H] THK-5351 binding to tau deposits with a high selectivity. Although patients with PSP exhibited no remarkable [18F] THK-5351 retention in the temporal cortex, significantly higher tracer retention was observed in the globus pallidus and midbrain. In contrast, amyloid imaging with Pittsburgh compound B showed no remarkable accumulation in the cerebral cortex of PSP. Conclusions We conclude that [18F] THK-5351 PET can potentially be used to detect the regional brain distribution of tau lesions in PSP, thereby facilitating the differential diagnosis of neurodegenerative disorders associated with tau protein. [ABSTRACT FROM AUTHOR]