Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Mov Disord. 2019 Jan;34(1):105-113. doi: 10.1002/mds.27546. Epub 2018 Nov 23.
Elevated uptake of the [ F]AV-1451 tau-PET ligand has been observed cross-sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [ F]AV-1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy.
Sixteen subjects with PSP underwent 2 serial [ F]AV-1451 tau-PET scans and 3-Tesla MRI over 12 months and were age- and sex-matched to 39 healthy controls with longitudinal [ F]AV-1451 PET. Median [ F]AV-1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo-controlled treatment trials were calculated.
Rate of midbrain atrophy was significantly increased in PSP compared with controls. [ F]AV-1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [ F]AV-1451 measures. Smallest sample-size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [ F]AV-1451 measures.
[ F]AV-1451 tau-PET measures increase over time in subjects with PSP, but longitudinal [ F]AV-1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials. © 2018 International Parkinson and Movement Disorder Society.
在进行性核上性麻痹（PSP）患者中，[ F]AV-1451 tau-PET 配体的摄取呈横断面升高。然而，尚不清楚该配体在 PSP 中的纵向表现如何。我们旨在确定[ F]AV-1451 PET 上的区域变化测量与更成熟的中脑萎缩率生物标志物相比，如何作为 PSP 的纵向生物标志物。
16 名 PSP 患者在 12 个月内接受了 2 次[ F]AV-1451 tau-PET 扫描和 3-Tesla MRI，并与 39 名具有纵向[ F]AV-1451 PET 的健康对照者按年龄和性别匹配。为每个扫描计算了大脑各区域的[ F]AV-1451 摄取中位数，并将其除以小脑 Crus 的摄取，以创建标准摄取值比。还计算了每个扫描的中脑体积。计算了进行安慰剂对照治疗试验所需的样本量。
与对照组相比，PSP 患者的中脑萎缩率明显增加。与对照组相比，PSP 患者的苍白球、中央前皮质、小脑齿状核和中脑的[ F]AV-1451 区域变化测量值明显增加。PSP 评定量表随时间的变化与中脑体积的变化相关，但与[ F]AV-1451 测量值的变化无关。从中脑萎缩率获得的最小样本量估计值，其次是 PSP 评定量表，两者的表现均优于[ F]AV-1451 测量值。
在 PSP 患者中，[ F]AV-1451 tau-PET 测量值随时间增加，但纵向[ F]AV-1451 测量值可能不如中脑萎缩率作为 PSP 临床试验的生物标志物。
