Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy
Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy
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DOI：
10.1001/jamaneurol.2020.2526
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发表时间：
2020-11-01
期刊：
影响因子：
29
通讯作者：
Sabri, Osama
中科院分区：
文献类型：
--
作者：
Brendel, Matthias;Barthel, Henryk;Sabri, Osama
重要性渐进性上核瘫（PSP）是4个重复的tauopathy。区域特异性TAU聚集体建立了明确的PSP验尸的神经病理诊断。对PSP中的TAU的未来介入试验将从支持诊断的生物标志物中受益匪浅。目的是研究新型Tau放射性示意剂F-18-PI-2620作为临床诊断PSP患者的生物标志物的潜力。设计，设置和参与者在这项横断面研究中，参与者在注射5个不同中心后0到60分钟接受了动态F-18-PI-2620正电子发射断层扫描（PET）（德国3，美国1个，1个，1和1在澳大利亚）。根据运动障碍社会的PSP标准，患有PSP患者（包括患有Richardson综合征[Rs]的患者）与健康的对照和疾病对照一起检查了PSP标准。由于不完整的动态PET扫描，将四个带有PSP-RS和2个具有PSP-NON-RS的个体引用的个体被排除在最终数据分析之外。从2016年12月到2019年10月收集了数据，并于2018年12月至2019年12月进行了分析。在独立的PSP-RS和健康对照样本中进行了验尸后的主要结果和措施。通过体内PET成像，在Globus pallidus Interus和外部，pe骨，丘脑下核，底底Nigra，背侧脑，齿状核，背侧外侧和内侧前额叶前皮质中获得了F-18-PI-2620分布量比。比较了PSP患者和对照组患者之间的PET数据，并因中心，年龄和性别而进行了校正。 60例PSP患者的结果40例（66.7％）的结果为卢比（22名男性[55.0％]；平均[SD]年龄，71 [6]年；平均[SD] PSP评分量表评分，38 [15]；得分范围，13-71）和20（33.3％）的PSP-NON-RS（11人[55.0％]；平均[SD]年龄，71 [9]年；平均[SD] PSP等级量表得分，24 [11]；十种健康对照（2人；平均[SD]年龄，67 [7]）和20种患有疾病的对照（10 [50.0％]患有帕金森氏病和多个系统萎缩，有7名男性；平均[SD]年龄，61岁[8]患有阿尔茨海默氏病的10 [50.0％]是男性；尸检后自显影术显示PSP患者的F-18-PI-2620结合可阻塞，并且在健康对照中无结合。 F-18-PI-2620的PSP中首次大规模观察性研究中的体内发现表明，PSP靶区域的示踪剂结合显着升高，在Interus球体中，PSP与对照组的差异最大（平均值[SD] [SD]分布量比：PSP-R，1.21 [0.10]； PSP-NON-RS，1.12 [0.11]； [0.08]；帕金森氏病/多系统萎缩，1.03 [0.05]；当使用至少1个正靶区域分类时，对PSP-RS与任何对照组的检测的敏感性和特异性分别为85％和77％。结论和相关性这个多中心评估表明，F-18-PI-2620的值可以区分可疑患者PSP的患者，并有可能促进PSP的更可靠的诊断。问题可以通过新型的Tau-Positron发射层析成像与新型的Tau positron发射层析成像成像-2620将进行性核上麻痹（PSP）患者与健康对照和疾病对照区分开。在这项对60例PSP患者，10个健康对照和20例疾病对照的横断面研究中，与对照组相比，PSP患者的靶区域的F-18-PI-2620结合显着更高，而与疾病严重程度相比。患有Richardson综合征的PSP的个别患者以高灵敏度和特异性分离。意思是F-18-PI-2620 Tau-Positron发射断层扫描将PSP患者与单患者水平的对照区分开，有可能促进更可靠的诊断。这项横断面研究研究了新型Tau Radiotracer F-18-PI的潜力-2620作为临床诊断性进行性核上麻痹的患者的生物标志物。
Importance Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective To investigate the potential of the novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants In this cross-sectional study, participants underwent dynamic F-18-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, F-18-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable F-18-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with F-18-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. Conclusions and Relevance This multicenter evaluation indicates a value of F-18-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.Question Can tau-positron emission tomography imaging with the novel tau radiotracer F-18-PI-2620 differentiate patients with progressive supranuclear palsy (PSP) from healthy controls and controls with disease? Findings In this cross-sectional study of 60 patients with PSP, 10 healthy controls, and 20 controls with disease, there was significantly higher F-18-PI-2620 binding in target regions of patients with PSP compared with controls regardless of disease severity. Individual patients with PSP with Richardson syndrome were separated with high sensitivity and specificity. Meaning F-18-PI-2620 tau-positron emission tomography differentiates patients with PSP from controls at the single-patient level, potentially facilitating a more reliable diagnosis.This cross-sectional study investigates the potential of novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed progressive supranuclear palsy.