Lockhart Samuel N, Baker Suzanne L, Okamura Nobuyuki, Furukawa Katsutoshi, Ishiki Aiko, Furumoto Shozo, Tashiro Manabu, Yanai Kazuhiko, Arai Hiroyuki, Kudo Yukitsuka, Harada Ryuichi, Tomita Naoki, Hiraoka Kotaro, Watanuki Shoichi, Jagust William J
Helen Wills Neuroscience Institute, University of California, Berkeley, California, United States of America.
Center of Functional Imaging, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
PLoS One. 2016 Jun 29;11(6):e0158460. doi: 10.1371/journal.pone.0158460. eCollection 2016.
[18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images.
Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer's disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR.
In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20-40, 30-50, and 40-60 min were most consistently correlated with DVR; SUVR 40-60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40-60 min signal, with no group differences.
We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40-60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.
[18F]THK5351是一种最近开发的用于测量tau神经原纤维缠结积聚的正电子发射断层扫描（PET）示踪剂，可能有助于研究人员检查活体人类大脑中的衰老、疾病和tau病理。我们研究了THK5351示踪剂的药代动力学，以确定静态晚期图像的最佳采集时间。
主要测量是计算6名健康老年对照者和10名阿尔茨海默病（AD）参与者的分布体积比（DVR）和标准化摄取值比（SUVR）的区域值。我们研究了DVR和SUVR之间的关联，寻找一个稳定且与DVR相当的20分钟SUVR时间窗。我们还研究了这个20分钟SUVR中的诊断组差异。
在健康对照者中，[18F]THK5351摄取较低，颞叶相对于额叶的结合增加。在AD患者中，区域摄取明显高于健康对照者，颞叶超过额叶结合。与其他区域相比，用作参考区域的小脑灰质中的滞留较低。40分钟后，DVR和SUVR值随时间的变化都很小。SUVR 20 - 40、30 - 50和40 - 60分钟与DVR的相关性最一致；SUVR 40 - 60分钟是最稳定的时间窗，用于进一步分析。颞顶叶区域存在显著的（AD > 健康对照）组间差异，内侧颞叶差异不显著。我们发现基底神经节SUVR 40 - 60分钟信号较高，无组间差异。
我们研究了用于测量tau积聚的新型PET示踪剂THK5351，并比较了多种定量区域示踪剂摄取的分析方法。在检查20分钟SUVR时间窗时，SUVR 40 - 60分钟表现最佳，似乎是一种定量相对区域示踪剂滞留的实用方法。鉴于THK5351 - PET作为衰老和疾病中tau病理生物标志物的有用性，本研究结果具有临床潜力。
