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Flortaucipir F 18 Tau PET 显像剂的测试-重测可重复性。

Test-Retest Reproducibility for the Tau PET Imaging Agent Flortaucipir F 18.

机构信息

Avid Radiopharmaceuticals, Inc. (a wholly owned subsidiary of Eli Lilly and Company), Philadelphia, Pennsylvania

Avid Radiopharmaceuticals, Inc. (a wholly owned subsidiary of Eli Lilly and Company), Philadelphia, Pennsylvania.

出版信息

J Nucl Med. 2018 Jun;59(6):937-943. doi: 10.2967/jnumed.117.200691. Epub 2017 Dec 28.

Abstract

Alzheimer disease (AD) is characterized by β-amyloid (Aβ) plaques and tau neurofibrillary tangles. There are several PET imaging biomarkers for Aβ including C-PiB and F-florbetapir. Recently, PET tracers for tau neurofibrillary tangles have become available and have shown utility in detection and monitoring of neurofibrillary pathology over time. Flortaucipir F 18 is one such tracer. Initial clinical studies indicated greater tau binding in AD and mild cognitive impairment patients than in controls in a pattern consistent with tau pathology observed at autopsy. However, little is known about the reproducibility of such findings. To our knowledge, this study reports the first data regarding test-retest reproducibility of flortaucipir F 18 PET. Twenty-one subjects who completed the study (5 healthy controls, 6 mild cognitive impairment, and 10 AD) received 370 MBq of flortaucipir F 18 and were imaged for 20 min beginning 80 min after injection and again at 110 min after injection. Follow-up (retest) imaging occurred between 48 h and 4 wk after initial imaging. Images were spatially normalized to Montreal Neurological Institute template space. SUVRs were calculated using AAL (Automated Anatomical Labeling atlas) volumes of interest (VOIs) for parietal, temporal, occipital, anterior, and posterior hippocampal, parahippocampal, and fusiform regions, as well as a posterior neocortical VOI composed of average values from parietal, temporal, and occipital areas. Further, a VOI derived by discriminant analysis that maximally separated diagnostic groups (multiblock barycentric discriminant analysis [MUBADA]) was used. All VOIs were referenced to a subsection of cerebellar gray matter (cere-crus) as well as a parametrically derived white matter-based reference region (parametric estimate of reference signal intensity [PERSI]). test, correlation analyses, and intraclass correlation coefficient were used to explore test-retest performance. Test-retest analyses demonstrated low variability in flortaucipir F 18 SUVR. The SD of mean percentage change between test and retest using the PERSI reference region was 2.22% for a large posterior neocortical VOI, 1.84% for MUBADA, 1.46% for frontal, 1.98% for temporal, 2.28% for parietal, and 3.27% for occipital VOIs. Further, significant correlations ( > 0.85; < 0.001) were observed for all regions, and intraclass correlation coefficient values (test-retest consistency) were greater than 0.92 for all regions. Significant test-retest reproducibility for flortaucipir F 18 was found across neocortical and mesial temporal lobe structures. These preliminary data suggest that flortaucipir F 18 tau imaging could be used to examine changes in tau burden over time.

摘要

阿尔茨海默病(AD)的特征是β-淀粉样蛋白(Aβ)斑块和 tau 神经原纤维缠结。有几种用于 Aβ的 PET 成像生物标志物,包括 C-PiB 和 F-氟比他哌。最近,tau 神经原纤维缠结的 PET 示踪剂已经问世,并在随时间推移检测和监测神经原纤维病理学方面显示出了实用性。氟曲沙班 F 18 就是这样一种示踪剂。初步的临床研究表明,AD 和轻度认知障碍患者的 tau 结合比对照组更高,这与尸检中观察到的 tau 病理学一致。然而,关于这些发现的可重复性知之甚少。据我们所知,这项研究报告了氟曲沙班 F 18 PET 首次测试-重测可重复性的数据。21 名完成研究的受试者(5 名健康对照、6 名轻度认知障碍和 10 名 AD)接受了 370 MBq 的氟曲沙班 F 18,并在注射后 80 分钟开始进行 20 分钟的成像,然后在注射后 110 分钟再次进行成像。随访(重测)成像在初始成像后 48 小时至 4 周之间进行。图像以蒙特利尔神经学研究所模板空间进行空间归一化。使用 AAL(自动解剖标记图谱)体积感兴趣区(VOI)计算 SUVR,用于顶叶、颞叶、枕叶、前叶和后海马、海马旁回和梭状回区域,以及由顶叶、颞叶和枕叶区域的平均值组成的后新皮质 VOI。此外,还使用了通过判别分析最大限度地区分诊断组的 VOI(多块重心判别分析 [MUBADA])。所有 VOI 均参考小脑灰质(小脑脚)以及参数衍生的基于白质的参考区域(参考信号强度的参数估计 [PERSI])。使用配对 t 检验、相关分析和组内相关系数来探索测试-重测性能。测试-重测分析表明氟曲沙班 F 18 SUVR 的变异性低。使用 PERSI 参考区域,测试和重测之间平均百分比变化的 SD 为大的后新皮质 VOI 的 2.22%,MUBADA 的 1.84%,额叶的 1.46%,颞叶的 1.98%,顶叶的 2.28%,枕叶的 3.27%。此外,所有区域均观察到显著的相关性(>0.85;<0.001),并且所有区域的组内相关系数值(测试-重测一致性)均大于 0.92。在新皮质和内侧颞叶结构中发现了氟曲沙班 F 18 的显著测试-重测可重复性。这些初步数据表明,氟曲沙班 F 18 tau 成像可用于检查 tau 负荷随时间的变化。

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