Head-to-head comparison of tau PET tracers [18F]PI-2620 and [18F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.
Matteo Tonietto, Oscar Sotolongo-Grau, Núria Roé-Vellvé, Santiago Bullich, Juan Pablo Tartari, Ángela Sanabria, Ainhoa García-Sánchez, Edilio Borroni, Christopher Galli, Esther Pérez-Martínez, Joan Castell-Conesa, Isabel Roca, Lluís Tárraga, Agustín Ruiz, Andrew W Stephens, Mercè Boada, Gregory Klein, Marta Marquié
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引用次数: 0
Abstract
Background: Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [18F]PI-2620 and [18F]RO948 in the early stages of the AD continuum.
Methods: Data from the TAU-PET FACEHBI clinical trial (EUDRA-CT 2021-000473-83) were analyzed. All participants were non-demented and underwent tau imaging with [18F]PI-2620 and [18F]RO948 PET within 3 months, amyloid imaging with [18F]Florbetaben and brain magnetic resonance imaging. Tau PET standardized uptake values ratios (SUVR) were calculated in Braak and typical off-target regions using the inferior cerebellar cortex as a reference region.
Results: The cohort consisted of 18 individuals with subjective cognitive decline (n = 13) and mild cognitive impairment (n = 5), with centiloid values ranging from 17 to 159. Both tau tracers showed similar tau pathology distribution but presented a distinct off-target signal pattern on visual read. SUVR measurements for [18F]PI-2620 and [18F]RO948 were highly correlated in all Braak regions (R2 range [0.65-0.80]). Regarding off-target signal, [18F]PI-2620 had higher SUVRs in vascular structures, and [18F]RO948 had higher SUVRs in the skull/meninges.
Conclusions: In a cohort of individuals at early stages of the AD continuum, tau PET tracers [18F]PI-2620 and [18F]RO948 showed similar in-vivo uptake in all Braak regions and distinct off-target signal. These preliminary results support the development of standardized quantification scales for tau deposition that are tracer-independent.
Trial registration: AEMPS EudraCT 2021-000473-83. Registered 30 December 2021.
背景：用于正电子发射断层扫描（PET）的第二代 tau 示踪剂对阿尔茨海默病特有的成对螺旋丝 tau 沉积物具有高亲和力，而脱靶结合率低。不过，它们化学结构的差异可能会导致其区域性 tau 吸收和脱靶信号的不同。在这项工作中，我们旨在比较tau示踪剂[18F]PI-2620和[18F]RO948在AD早期阶段的体内摄取情况：分析了TAU-PET FACEHBI临床试验（EUDRA-CT 2021-000473-83）的数据。所有参与者均未痴呆，并在3个月内接受了[18F]PI-2620和[18F]RO948 PET的tau成像、[18F]Florbetaben的淀粉样蛋白成像和脑磁共振成像。以小脑下皮层为参照区域，计算布拉克和典型脱靶区域的 Tau PET 标准化摄取值比（SUVR）：研究对象包括18名主观认知能力下降患者（13人）和轻度认知障碍患者（5人），中心值从17到159不等。两种tau示踪剂显示出相似的tau病理分布，但在视觉读数上呈现出明显的脱靶信号模式。[18F]PI-2620和[18F]RO948的SUVR测量值在所有Braak区域都高度相关（R2范围为[0.65-0.80]）。关于脱靶信号，[18F]PI-2620在血管结构中的SUVR较高，而[18F]RO948在颅骨/脑膜中的SUVR较高：结论：在一组处于AD早期阶段的个体中，tau PET示踪剂[18F]PI-2620和[18F]RO948在所有Braak区域显示出相似的体内摄取和不同的脱靶信号。这些初步结果支持开发与示踪剂无关的tau沉积标准化量化标度：试验注册：AEMPS EudraCT 2021-000473-83。注册日期：2021 年 12 月 30 日。
期刊介绍：
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.
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