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
{"title":"在有脑淀粉样蛋白沉积的非痴呆症患者中对tau PET示踪剂[18F]PI-2620和[18F]RO948进行头对头比较:TAU-PET FACEHBI队列。","authors":"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","doi":"10.1186/s13195-024-01622-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 in the early stages of the AD continuum.</p><p><strong>Methods: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 PET within 3 months, amyloid imaging with [<sup>18</sup>F]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.</p><p><strong>Results: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 were highly correlated in all Braak regions (R<sup>2</sup> range [0.65-0.80]). Regarding off-target signal, [<sup>18</sup>F]PI-2620 had higher SUVRs in vascular structures, and [<sup>18</sup>F]RO948 had higher SUVRs in the skull/meninges.</p><p><strong>Conclusions: </strong>In a cohort of individuals at early stages of the AD continuum, tau PET tracers [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]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.</p><p><strong>Trial registration: </strong>AEMPS EudraCT 2021-000473-83. Registered 30 December 2021.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"257"},"PeriodicalIF":7.9000,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603960/pdf/","citationCount":"0","resultStr":"{\"title\":\"Head-to-head comparison of tau PET tracers [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.\",\"authors\":\"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\",\"doi\":\"10.1186/s13195-024-01622-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 in the early stages of the AD continuum.</p><p><strong>Methods: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 PET within 3 months, amyloid imaging with [<sup>18</sup>F]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.</p><p><strong>Results: </strong>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 [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]RO948 were highly correlated in all Braak regions (R<sup>2</sup> range [0.65-0.80]). Regarding off-target signal, [<sup>18</sup>F]PI-2620 had higher SUVRs in vascular structures, and [<sup>18</sup>F]RO948 had higher SUVRs in the skull/meninges.</p><p><strong>Conclusions: </strong>In a cohort of individuals at early stages of the AD continuum, tau PET tracers [<sup>18</sup>F]PI-2620 and [<sup>18</sup>F]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.</p><p><strong>Trial registration: </strong>AEMPS EudraCT 2021-000473-83. 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引用次数: 0
摘要
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。
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.
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.
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.