Comparison of Two Next Generation TAU Radiopharmaceuticals in Alzheimer's Disease

两种下一代 TAU 放射性药物治疗阿尔茨海默病的比较

• 批准号: 10190454
• 负责人: HIROTO KUWABARA
• 金额: $ 19.19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10190454
• 关键词: Affinity; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid beta-Protein; Applications Grants; Basal Ganglia; Binding; Brain; Cerebellum; Chemical Structure; Cognitive; Collaborations; Complement; Dementia; Discrimination; Evaluation; Future; Goals; Head; Hippocampus (Brain); Human; Image; In Vitro; Incidence; Inferior; Kinetics; Lead; Literature; Mao-to; Measures; Modeling; Monoamine Oxidase A; Monoamine Oxidase B; Neurofibrillary Tangles; Pathology; Pattern; Pharmacology; Positron-Emission Tomography; Radiopharmaceuticals; Reporting; Research; Research Design; Research Personnel; Role; Series; Specificity; Standardization; Structure; Structure of choroid plexus; Study Subject; Tauopathies; Thalamic structure; Time; Tracer; Treatment Protocols; clinical Diagnosis; design; gray matter; innovation; interest; neuroimaging; next generation; radioligand; tau Proteins; tau aggregation; time interval; tool; trait; uptake; white matter

Project Summary This study will be the first of its kind globally, comparing [18F]RO-948, a radiopharmaceutical developed from an extensive series of well-characterized tau radioligands by Wong/Kuwabara MPIs with an increasingly used next-generation radiopharmaceutical, [18F]MK-6240. The primary aim of which would be to identify a more optimal radioligand for tau imaging of tauopathy in Alzheimer’s disease (AD) through direct comparisons of these two potential candidates, and demonstration of their lack of off target binding which is suffered by commonly used [18F]AV1451. These next generation radiopharmaceuticals ([18F]MK-6240 and [18F]RO-948) both have a different chemical structure and somewhat different pharmacologic profile; therefore, we anticipate definitive differences in distribution volume ratios, standardized uptake ratios at optimal delayed imaging times and off-target binding. Ten subjects with Alzheimer’s disease, diagnosed by Alzheimer’s Disease Research Center (ADRC) and/or DSM criteria will be studied with both radiopharmaceuticals. We hypothesize these tracers to show similarly good results in the kinetic evaluations, specifically that [18F]RO-948 shows lower binding than [18F]MK-6240 in the cerebellum and white matter regions and is associated with better discrimination of AD subjects from healthy controls. Additionally we will examine these next-generation tracers in terms of off-target binding potential within the basal ganglia, thalamus, and choroid plexus; hypothesizing lower binding than that of the currently regarded [18F]AV1451. If supported, these hypotheses will provide a rationale for selecting [18F]RO-948 or [18F]MK-6240 compared to [18F]AV1451 for studying tau accumulation in AD. It is critical to demonstrate which radioligand is better for discrimination of AD from OC in the proposed same-subject design, as well as, examine potential for off-target binding. This innovative comparison of the three radioligands in head-to-head interrogation will yield critical information for selection of radioligands for research in the field of neuroimaging of tau.

项目摘要 这项研究将是全球首个此类研究，比较了[18F]RO-948，一种从 由Wong/Kuwabara MPIs开发的一系列表征良好的tau放射性配体，具有越来越多的使用 下一代放射性药物，[18F]MK-6240。其主要目的将是找出更多 阿尔茨海默病(AD)tau显像的最佳放射性配基 这两个潜在的候选人，并表明他们缺乏脱离目标的约束，这是遭受 常用的[18F]AV1451。这些新一代放射性药物([18F]MK-6240和[18F]RO-948) 两者都有不同的化学结构和略有不同的药理特征；因此，我们预计 最佳延迟成像时间的分布体积比、标准化摄取比的明确差异 和脱离目标的绑定。10名阿尔茨海默病患者，由阿尔茨海默病研究公司诊断 中心(ADRC)和/或DSM标准将与这两种放射性药物一起研究。我们假设这些 示踪剂在动力学评估中显示出类似的良好结果，特别是[18F]RO-948显示较低 在小脑和白质区域比[18F]MK-6240结合更好 阿尔茨海默病患者与健康对照组的区别。此外，我们还将检查这些下一代示踪剂 就基底节、丘脑和脉络丛内的非靶点结合潜力而言；假设 比目前认为的[18F]AV1451具有更低的结合强度。如果得到支持，这些假设将提供一种 选择[18F]RO-948或[18F]MK-6240与[18F]AV1451比较研究牛磺酸在 广告。在建议的研究中，证明哪种放射性配基更适合区分AD和OC是至关重要的 同主题设计，以及，检查目标外绑定的可能性。这一创新的比较 三个放射性配基在面对面的讯问中将产生关键信息，用于选择 Tau的神经成像领域的研究。