Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study
Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study
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DOI：
10.2967/jnumed.119.236224
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发表时间：
2020-06-01
影响因子：
9.3
通讯作者：
Stephens, Andrew W.
中科院分区：
文献类型：
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作者：
Mueller, Andre;Bullich, Santiago;Stephens, Andrew W.
F-18-PI-2620是一种对聚集的tau具有高结合亲和力的PET示踪剂，tau是阿尔茨海默病(AD)和其他神经退行性疾病的关键病理特征。临床前，F-18-PI-2620可与3-重复和4-重复tau亚型结合。这项首次人体研究的目的是评估F-18-PI-2620使用PET成像检测AD患者tau病理的能力，以及评估这种新的tau PET示踪剂的安全性和耐受性。方法：对临床诊断为阿尔茨海默病的受试者和健康对照组(HCS)进行180min的F-18-PI-2620PET动态显像。以小脑皮质为参照区，用无创性示踪动力学计算的分布体积比(DVR)和注射后不同时间点测量的SUV比(SUVR)对F-18-PI-2620的结合进行直观和定量的评价。评估AD和HC患者的时间-活动曲线和SUVR，以及随着时间的推移DVR和SUVR的相关性和效应大小(Cohen‘s d)。结果：F-18-PI-2620在注射后5min左右出现脑摄取高峰，非靶区吸收迅速。在AD患者中，局灶性不对称摄取明显存在于颞叶和顶叶、楔前叶和后扣带皮质。AD组上述区域的DVR和SUVR显著高于HCS组。HCS的背景信号很低。F-18-PI-2620给药安全、耐受性好。注射后40min，大部分区域和受试者的SUVR时间-活动曲线达到长期平衡。在注射后30min以上的所有成像窗口中，无创性DVR和SUVR之间存在很强的相关性(R-2>；0.93)。AD组和HC组在不同的成像窗口中获得了相似的效应大小。F-18-PI-2620在新皮质区域的摄取与认知损害程度显著相关。结论：AD和HC患者的初步临床数据显示，F-18-PI-2620PET成像AD患者tau沉积具有较高的图像质量和良好的信噪比。在注射后30至90分钟(例如45至75分钟)，使用DVR和SUVR对30分钟的成像窗口进行无创量化，可在AD和HC受试者之间提供强有力且显著的区分。F-18-PI-2620在预期区域的摄取与神经认知表现密切相关。
F-18-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative disorders. Preclinically, F-18-PI-2620 binds to both 3-repeat and 4-repeat tau isoforms. The purpose of this first-in-humans study was to evaluate the ability of F-18-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess the safety and tolerability of this new tau PET tracer. Methods: Participants with a clinical diagnosis of probable AD and healthy controls (HCs) underwent dynamic F-18-PI-2620 PET imaging for 180 min. F-18-PI-2620 binding was assessed visually and quantitatively using distribution volume ratios (DVR) estimated from noninvasive tracer kinetics and SUV ratio (SUVR) measured at different time points after injection, with the cerebellar cortex as the reference region. Time-activity curves and SUVR were assessed in AD and HC subjects, as well as DVR and SUVR correlations and effect size (Cohen's d) over time. Results: F-18-PI-2620 showed peak brain uptake around 5 min after injection and fast washout from nontarget regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD subjects than in HCs. Very low background signal was observed in HCs. F-18-PI-2620 administration was safe and well tolerated. SUVR time-activity curves in most regions and subjects achieved a secular equilibrium after 40 min after injection. A strong correlation (R-2 > 0.93) was found between noninvasive DVR and SUVR for all imaging windows starting at more than 30 min after injection. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. F-18-PI-2620 uptake in neocortical regions significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC subjects demonstrated a high image quality and excellent signal-to-noise ratio of F-18-PI-2620 PET for imaging tau deposition in AD subjects. Noninvasive quantification using DVR and SUVR for 30-min imaging windows between 30 and 90 min after injection-for example, 45-75 min-provides robust and significant discrimination between AD and HC subjects. F-18-PI-2620 uptake in expected regions correlates strongly with neurocognitive performance.