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tau PET 成像与 [18F]PM-PBB3 在伴有 MAPT 突变的额颞叶痴呆。

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation.

机构信息

Department of Neurology, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.

PET Centre, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

J Alzheimers Dis. 2020;76(1):149-157. doi: 10.3233/JAD-200287.

Abstract

BACKGROUND

Flortaucipir (AV-1451) and pyridinyl-butadienyl-benzothiazole 3 (PBB3) are newly developed and commonly used positron emission tomography (PET) tracers to detect tau deposition in tauopathies, including frontotemporal dementia (FTD). [18F]PM-PBB3, as a second-generation compound, has not been described in FTD so far.

OBJECTIVE

We aim to explore the in vivo performance of [18F]PM-PBB3 tau PET in an FTD case caused by microtubule-associated protein tau (MAPT) mutation and compare the binding to different tau strains between AV-1451 and PBB3.

METHODS

We reported the clinical and FDG, [18F]AV45 amyloid and [18F]PM-PBB3 tau PET findings in a patient with FTD of P301L MAPT mutation. Based on our results and published data, we summarized and compared the different utilities of tau PET tracers of AV-1451 and PBB3 in FTD with MAPT mutation.

RESULTS

The patient demonstrated slightly diffuse [18F]PM-PBB3 tau deposition in cerebral lobes especially in the left frontal lobe overlapping with the hypometabolic region detected by FDG PET. From our analysis of 35 FTD patients with MAPT mutation who underwent tau PET, AV-1451 was positive in all (n = 11) patients with mutations known to cause three and four repeat (3R/4R) tau deposition and in 14.3% (n = 2/14) of 4R tauopathies, while positive PBB3 retention was found in all patients with both 3R/4R (n = 2) and 4R (n = 8) tau.

CONCLUSIONS

[18F]PM-PBB3 tau PET assisted the diagnosis of FTD with P301L MAPT mutation, and might be useful in the in vivo detection of both 3R/4R and 4R tau domains in the brain of FTD with MAPT mutation.

摘要

背景

Flortaucipir(AV-1451)和吡啶基-丁二烯基-苯并噻唑 3(PBB3)是新开发并常用于正电子发射断层扫描(PET)来检测包括额颞叶痴呆(FTD)在内的tau 蛋白沉积的示踪剂。[18F]PM-PBB3,作为第二代化合物,目前尚未在 FTD 中描述。

目的

我们旨在探索 [18F]PM-PBB3 tau PET 在由微管相关蛋白 tau(MAPT)突变引起的 FTD 病例中的体内表现,并比较 AV-1451 和 PBB3 之间对不同 tau 株的结合。

方法

我们报告了一例 P301L MAPT 突变引起的 FTD 患者的临床和 FDG、[18F]AV45 淀粉样蛋白和 [18F]PM-PBB3 tau PET 结果。基于我们的结果和已发表的数据,我们总结并比较了 AV-1451 和 PBB3 在 FTD 伴 MAPT 突变中的 tau PET 示踪剂的不同用途。

结果

患者在大脑叶,特别是在左侧额叶显示出轻微弥漫性[18F]PM-PBB3 tau 沉积,与 FDG PET 检测到的代谢低下区域重叠。从我们对 35 例伴 MAPT 突变的 FTD 患者进行的 tau PET 分析中,AV-1451 在所有已知引起三重复(3R)/四重复(4R)tau 沉积的突变(n=11)患者中均为阳性,在 4R tau 病变的 14.3%(n=14)患者中也为阳性,而阳性 PBB3 保留在所有 3R/4R(n=2)和 4R(n=8)tau 的患者中均被发现。

结论

[18F]PM-PBB3 tau PET 辅助了 P301L MAPT 突变的 FTD 诊断,并且可能有助于在 FTD 伴 MAPT 突变的大脑中检测到 3R/4R 和 4R tau 域的体内检测。

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