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Tau PET imaging in atypical parkinsonian disorders
https://repo.qst.go.jp/records/74897
https://repo.qst.go.jp/records/74897f8380624-8481-4a68-a962-372d66e084e1
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-03-20 | |||||
| タイトル | ||||||
| タイトル | Tau PET imaging in atypical parkinsonian disorders | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
島田, 斉
× 島田, 斉× Shimada, Hitoshi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | BACKGROUND: In addition to synucleinopathies, 4-repeat tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) hold a prominent position in atypical parkinsonian disorders. 11C-pyridinylbutadienyl-benzothiazole 3 (11C-PBB3), a tau PET ligand, binds to a wide range of tau fibrils including Alzheimer’s disease (AD), non-AD tauopathies, and transgenic mice tau deposits. We have developed a 18F-labeled PBB3 derivative, 18F-PM-PBB3 (18F-APN-1607), to improve imaging characteristics of 11C-PBB3 and wider availability. The present study aimed to evaluate the potential utility of 18F-PM-PBB3 in patients with atypical parkinsonian disorders. METHODS: To characterize the binding property of 18F-PM-PBB3 to diverse tau inclusions, we performed preclinical evaluations of 18F-PM-PBB3 using brain samples of humans and model mice. Furthermore, we conducted a clinical PET study. 20 patients with Parkinson’s disease (PD) and related atypical parkinsonian disorders, including PSP and corticobasal syndrome (CBS), seven AD spectrum patients and 29 cognitively healthy controls (HCs) were recruited. PET scans with 18F-PM-PBB3 and 11C-PiB were performed to estimate regional tau and amyloid-β loads. We generated parametric images of standardized uptake value ratio (SUVR) to the cerebellar cortex for 18F-PM-PBB3 and 11C-PiB to evaluate brain regional tau and amyloid-β loads. RESULTS: Preclinical characterization revealed that 18F-PM-PBB3 can bind diverse tau pathologies, including AD, PSP, CBD, and Pick’s disease, with high sensitivity and specificity. It was also demonstrated that 18F-PM-PBB3 cross-reacts with neither monoamine oxidase (MAO)-A nor MAO-B. In the clinical PET study, 18F-PM-PBB3 did not produce prominent off-target signals in the basal ganglia. PiB-negative patients with 4-repeat tauopathies showed remarkable uptake of PM-PBB3 especially around subthalamic nucleus, basal ganglia, midbrain including nigra and red nucleus, and dentate nucleus, whereas PiB-negative PD did not show any prominent uptake of PM-PBB3. Compared with PSP with Richardson syndrome, patients with other variants of PSP and CBS showed relatively milder PM-PBB3 uptake especially around the midbrain. In contrast, patients with 4-repeat tauopathies having verbal and/or behavioral symptoms also presented elevated PM-PBB3 uptake in some cortices as well as the above-mentioned regions. Patients with 4-repeat tauopathies were easily differentiated from PD and AD spectrum patients as well as HCs both by visual assessment and quantitative comparison of SUVR values in certain brain regions. CONCLUSIONS: 18F-PM-PBB3 is a promising PET ligand for quantifying tau pathologies in 4-repeat tauopathies patients as well as AD spectrum patients with high contrast and minimal parenchymal off-target binding. Accumulations of PM-PBB3 may reflect characteristic distributions of tau pathologies in 4-repeat tauopathies, in conjunction with clinical manifestations. The present study provides further evidence for the potential utility of 18F-PM-PBB3 PET in tracking 4-repeat tau pathologies, which may facilitate better understanding of pathological basis and drug development in atypical parkinsonian disorders. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Takeda PD Symposium | |||||
| 発表年月日 | ||||||
| 日付 | 2019-01-12 | |||||
| 日付タイプ | Issued | |||||
