一种用于阿尔茨海默病的新型tau成像示踪剂的体内评估。
In vivo evaluation of a novel tau imaging tracer for Alzheimer's disease.
作者信息
Villemagne Victor L, Furumoto Shozo, Fodero-Tavoletti Michelle T, Mulligan Rachel S, Hodges John, Harada Ryuichi, Yates Paul, Piguet Olivier, Pejoska Svetlana, Doré Vincent, Yanai Kazuhiko, Masters Colin L, Kudo Yukitsuka, Rowe Christopher C, Okamura Nobuyuki
机构信息
Centre for PET, Austin Health, Melbourne, Australia,
出版信息
Eur J Nucl Med Mol Imaging. 2014 May;41(5):816-26. doi: 10.1007/s00259-013-2681-7. Epub 2014 Feb 11.
PURPOSE
Diagnosis of tauopathies such as Alzheimer's disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate (18)F-THK523 as a potential tau imaging tracer.
METHODS
Ten healthy elderly controls, three semantic dementia (SD) and ten AD patients underwent neuropsychological examination, MRI as well as (18)F-THK523 and (11)C-Pittsburgh compound B (PIB) positron emission tomography (PET) scans. Composite memory and non-memory scores, global and hippocampal brain volume, and partial volume-corrected tissue ratios for (18)F-THK523 and (11)C-PIB were estimated for all participants. Correlational analyses were performed between global and regional (18)F-THK523, (11)C-PIB, cognition and brain volumetrics.
RESULTS
(18)F-THK523 presented with fast reversible kinetics. Significantly higher (18)F-THK523 retention was observed in the temporal, parietal, orbitofrontal and hippocampi of AD patients when compared to healthy controls and SD patients. White matter retention was significantly higher than grey matter retention in all participants. The pattern of cortical (18)F-THK523 retention did not correlate with Aβ distribution as assessed by (11)C-PIB and followed the known distribution of tau in the AD brain, being higher in temporal and parietal areas than in the frontal region. Unlike (11)C-PIB, hippocampal (18)F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy.
CONCLUSION
(18)F-THK523 does not bind to Aβ in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain. Significantly higher cortical (18)F-THK523 retention in AD patients as well as the association of hippocampal (18)F-THK523 retention with cognitive parameters and hippocampal volume suggests (18)F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high (18)F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.
目的
诸如阿尔茨海默病（AD）等tau蛋白病的诊断仍依赖于对人脑进行尸检。一种在体内测定脑tau蛋白负荷的非侵入性方法将有助于更好地理解tau蛋白病的病理生理学。本研究的目的是评估（18）F-THK523作为一种潜在的tau蛋白成像示踪剂。
方法
10名健康老年对照者、3名语义性痴呆（SD）患者和10名AD患者接受了神经心理学检查、MRI以及（18）F-THK523和（11）C-匹兹堡化合物B（PIB）正电子发射断层扫描（PET）。对所有参与者估计了综合记忆和非记忆评分、全脑和海马脑容量以及（18）F-THK523和（11）C-PIB的部分容积校正组织比率。对全脑和局部的（18）F-THK523、（11）C-PIB、认知和脑容量测量进行了相关性分析。
结果
（18）F-THK523表现出快速可逆的动力学。与健康对照者和SD患者相比，AD患者的颞叶、顶叶、眶额和海马区观察到显著更高的（18）F-THK523滞留。所有参与者中白质滞留显著高于灰质滞留。通过（11）C-PIB评估，皮质（18）F-THK523滞留模式与Aβ分布无关，且遵循AD脑中已知的tau蛋白分布，颞叶和顶叶区域高于额叶区域。与（11）C-PIB不同，海马区（18）F-THK523滞留与多个认知参数以及海马萎缩相关。
结论
（18）F-THK523在体内不与Aβ结合，同时遵循脑中已知的成对螺旋丝（PHF）-tau蛋白分布。AD患者皮质（18）F-THK523滞留显著更高，以及海马区（18）F-THK523滞留与认知参数和海马体积的关联表明（18）F-THK523在AD患者中选择性地与tau蛋白结合。不幸的是，白质中（18）F-THK523滞留非常高，妨碍了对图像的简单目视检查，使其无法用于研究或临床环境。
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