18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION
18F-PI2620 TAU-PET IN PROGRESSIVE SUPRANUCLEAR PALSY: A MULTI-CENTER EVALUATION
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18F-PI2620 TAU-PET 在进行性核上性麻痹中的应用：多中心评估
DOI：
10.1016/j.jalz.2019.06.4276
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
O. Sabri
中科院分区：
文献类型：
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作者：
M. Brendel;H. Barthel;T. Eimeren;K. Marek;L. Beyer;M. Song;Carla Palleis;G. Respondek;J. Sauerbeck;J. Hammes;M. Barbe;O. Onur;F. Jessen;D. Saur;M. Schroeter;Jost;M. Rullmann;A. Schildan;M. Patt;O. Barret;Jennifer Madonia;David W. Russell;A. Stephens;S. Roeber;J. Herms;K. Boetzel;J. Levin;J. Classen;G. Höglinger;P. Bartenstein;A. Drzezga;J. Seibyl;O. Sabri
进行性核上性麻痹（PSP）是一种4重复（4R） tau病变，区域特异性tau沉积建立了“明确PSP”的尸检神经病理学诊断。未来针对PSP中tau蛋白的介入试验将从生物标记物中获益，以在治疗开始前验证靶点的特异性存在。新的第二代tau- pet配体18f - pi2620被证明在阿尔茨海默病（AD）中不存在单胺氧化酶的脱靶结合和对3/4R tau的高亲和力。这项多中心评估的目的是研究18个F-PI2620在临床诊断为PSP的疑似4R tau病理患者中的作用。方法18例（70±6岁，n= 9名女性）符合MDS-PSP标准的疑似PSP Richardson综合征患者在4个不同的中心接受了18次F-PI2620 PET检查，并与10名健康对照和10名疾病对照（多系统萎缩、帕金森病和AD）。采用小脑尺度法生成皮质下脑区标准摄取值比（SUVr, 30-60min）。比较PSP、HC和疾病对照的SUVr数据。在PSP和HC之间进行统计参数映射（SPM, V12）。对不同中心的SUVr和SPM数据进行校正。采用18f - pi2620对脑切片进行体外先导放射自显影。结果PSP患者在苍白球（1.34±0.16,p= 0.001, d= 1.72）和黑质（1.33±0.13,p= 0.002, d= 1.52）的18 F-PI2620 SUVr水平明显高于HC(1.12±0.09/1.15±0.08)（PSP评分范围：40±17，范围13-71）。与HC相比，疾病对照组在苍白球（1.12±0.08;p= ns）和黑质（1.25±0.10;p= ns）中显示类似的信号。SPM显示，与HC相比，苍白球、黑质、额叶和顶叶皮质的18 F-PI2620摄取升高（均p< 0.001，未经校正）。与HC相比，疾病严重程度较低的受试者（PSP评分量表≤30；n= 4）苍白球18 F-PI2620摄取已显著升高（1.38±0.13;p= 0.001; d= 2.32）。初步体外放射自显像显示PSP患者苍白球中有明显的18f - pi2620结合，但与AD患者的皮质结合相比较低。结论本初步多中心评价提示18 F-PI2620对疑似PSP患者的诊断和鉴别有一定价值，可促进PSP的早期诊断和更可靠的诊断。
BackgroundProgressive supranuclear palsy (PSP) is a 4-repeat (4R) tauopathy and region-specific tau deposits establish the neuropathological diagnosis of “definite PSP” post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers to validate the specific presence of the target before therapy initiation. The novel second generation tau-PET ligand 18 F-PI2620 proved absent off-target binding to monoamine oxidases and high affinity to 3/4R tau in Alzheimer's disease (AD). The aim of this multicenter-evaluation was to investigate 18 F-PI2620 in patients with suspected 4R tau pathology in clinically diagnosed PSP.MethodsEighteen patients (70±6y, n= 9 female) with probable or possible PSP Richardson syndrome according to MDS-PSP criteria underwent 18 F-PI2620 PET at four different centers together with ten healthy controls and ten disease controls (Multi-system atrophy, Parkinson's disease, and AD). Standardized uptake value ratios (SUVr, 30-60min) of predefined subcortical brain regions were generated using cerebellar scaling. SUVr data were compared between PSP, HC, and disease controls. Statistical parametric mapping (SPM, V12) was performed between PSP and HC. SUVr and SPM data were corrected for different centers. An in vitro pilot autoradiography using 18 F-PI2620 incubation of brain slices was performed.ResultsElevated 18 F-PI2620 SUVr was observed in PSP patients (PSP rating scale: 40±17; range 13-71) in the globus pallidus (1.34±0.16; p= 0.001; d= 1.72) and the substantia nigra (1.33±0.13; p= 0.002; d= 1.52) when compared to HC (1.12±0.09/1.15±0.08). Disease controls showed a similar signal in the globus pallidus (1.12±0.08; p= ns) and a moderate elevation in the substantia nigra (1.25±0.10; p= ns) when compared to HC. SPM revealed elevated 18 F-PI2620 uptake in the globus pallidus, in the substantia nigra, and frontal and parietal cortices (all p< 0.001, uncorrected) as compared to HC. Subjects with low disease severity (PSP rating scale≤ 30; n= 4) already had a significantly elevated 18 F-PI2620 uptake in the globus pallidus when compared to HC (1.38±0.13; p= 0.001; d= 2.32). Preliminary in vitro autoradiography showed distinguishable 18 F-PI2620 binding in the globus pallidus of a PSP patient which was however lower when compared to cortical binding in AD.ConclusionsThis preliminary multi-center evaluation indicates a value of 18 F-PI2620 to diagnose and differentiate suspected PSP patients, may facilitating earlier and more reliable diagnosis of PSP.