Simple In Vivo PET Measure of Amyloid Binding in AD

AD 中淀粉样蛋白结合的简单体内 PET 测量

• 批准号: 6767220
• 负责人: Julie C Price
• 金额: $ 39.08万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-13 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767220
• 关键词: Alzheimer' s disease; amyloid proteins; bioimaging /biomedical imaging; biomarker; brain imaging /visualization /scanning; brain mapping; brain metabolism; clinical research; computer simulation; dementia; early diagnosis; glucose metabolism; hemodynamics; human subject; magnetic resonance imaging; method development; patient oriented research; positron emission tomography; protein binding; radiotracer

DESCRIPTION (provided by applicant): At present, the definitive diagnosis of Alzheimer's disease (AD) is based on the pathologic confirmation of amyloid plaques and neurofibrillary tangles in the cerebral cortex. Over many years, our research efforts have been directed toward the development of non-invasive methods for the in vivo measurement of amyloid plaques. Toward this goal, our group recently collaborated with researchers in Uppsala, Sweden, to perform the first human positron emission tomography (PET) studies of a new amyloidbinding radiotracer, named PIB (Pittsburgh Compound B). These first human studies demonstrated high PIB retention in AD subjects (n=9) in brain areas known to have high amyloid levels in AD (relative to controls, n=5). The next step in our efforts is to establish the validity of the PIB PET methodology and to determine a valid and simple method for potential clinical use. The central goal of this application is to validate the PIB PET methodology and identify a simple PIB measure of amyloid-binding that is feasible for routine use. Toward this goal, PIB PET studies will be acquired in 3 subject groups: mild-to-moderate AD dementia (n=12), mild cognitive impairment (n=12), and elderly controls (n=12). PIB localization will be related to measures of brain glucose metabolism (using [18F]FDG), which has been extensively used as a metabolic index of AD. Validation will include acquisition of [15O]water PET data to exclude the influence of variations in blood flow on PIB binding. Structural MRI data will be acquired in all subjects to provide anatomical guidance for the PET data analyses. Our first aim is to identify an optimal fully-quantitative (arterial blood) PIB PET method. The second aim is to choose a valid and simple (no blood sampling) PIB PET method based upon the fully-quantitative data and an iterative evaluation of observed and computer-simulated PIB data. The simple method will allow rapid generation of robust image maps of amyloid binding throughout brain. The final aim is to relate anatomically standardized maps of amyloid binding to maps of cerebral metabolism. This research will provide important groundwork to support the use of the PIB measure of amyloid binding in early and pre-clinical diagnosis of AD and potentially accelerate the development and evaluation of important new therapies for dementia.

描述（由申请人提供）： 目前，对阿尔茨海默氏病（AD）的明确诊断是基于大脑皮层淀粉样蛋白斑块和神经原纤维缠结的病理证实。多年来，我们的研究工作一直致力于开发非侵入性方法，用于淀粉样蛋白斑的体内测量。为了实现这一目标，我们的小组最近与瑞典Uppsala的研究人员合作，对新的淀粉样蛋白放射性固定剂（PIBSBURGH GOMPLACER（匹兹堡化合物B）进行了首次人类正电子发射断层扫描（PET）研究。这些首次人类研究表明，在已知AD中具有较高淀粉样蛋白水平的大脑区域的AD受试者（n = 9）中的PIB保留率很高（相对于对照，n = 5）。我们努力的下一步是建立PIB PET方法论的有效性，并确定一种有效而简单的潜在临床用途方法。 该应用程序的核心目标是验证PIB PET方法论，并确定一个简单的PIB衡量淀粉样蛋白结合的测量，这对于常规使用是可行的。为了实现这一目标，PIB PET研究将在3个受试者组中获得：轻度至中度的AD痴呆（n = 12），轻度认知障碍（n = 12）和老年对照（n = 12）。 PIB定位将与脑葡萄糖代谢的度量有关（使用[18F] FDG），该代谢已被广泛用作AD的代谢指数。验证将包括获取[15O]水PET数据，以排除血流变化对PIB结合的影响。将在所有受试者中获取结构性MRI数据，以为PET数据分析提供解剖学指南。我们的第一个目的是确定最佳的全毒性（动脉血）PIB PET方法。第二个目的是根据完全定量数据选择有效且简单的（无血液采样）PIB PET方法，并对观察到的和计算机模拟的PIB数据进行迭代评估。简单的方法将允许在整个大脑中快速生成淀粉样蛋白结合的强大图像图。最终目的是将淀粉样蛋白结合的解剖标准化图与脑代谢图相关联。这项研究将提供重要的基础，以支持在AD的早期和临床前诊断中使用PIB测量淀粉样蛋白结合的方法，并有可能加速对痴呆症的重要新疗法的发展和评估。