Utility of Early Phase PIB as a Surrogate for Cerebral Blood Flow Measures

早期 PIB 作为脑血流测量替代品的实用性

• 批准号: 8675997
• 负责人: LAURA LYNN BOLES PONTO
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8675997
• 关键词: Address; Alzheimer' s Disease; Amyloid; Behavior; Biological Markers; Blood Vessels; Blood flow; Cerebrovascular Circulation; Cerebrovascular Disorders; Clinical; Computer software; Development; Diabetes Mellitus; Feasibility Studies; Female; Functional disorder; Genotype; Goals; Gold; Hyperlipidemia; Hypertension; Image; Image Analysis; Impaired cognition; Investigation; Kinetics; Label; Link; Measures; Metabolic; Methodology; Metric; Modeling; Participant; Pathology; Patients; Phase; Populations at Risk; Positron-Emission Tomography; Procedures; Relative (related person); Reporting; Research; Research Design; Research Project Grants; Rest; Risk; Risk Factors; Sampling; Scanning; Staging; Techniques; Tracer; Water; Work; amyloid imaging; amyloid pathology; apolipoprotein E-4; base; cardiovascular risk factor; cerebrovascular; fluorodeoxyglucose; glucose uptake; male; public health relevance; radiotracer; tool; treatment effect; uptake

DESCRIPTION (provided by applicant): Cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, apolipoprotein e4 genotype) and cerebrovascular dysfunction are associated with an enhanced risk for the development of Alzheimer's Disease (AD). Therefore, assessments of developing Alzheimer's pathology should ideally address both cerebrovascular function as well as amyloid pathology. Positron emission tomography (PET) is capable of quantifying both attributes through cerebral blood flow and amyloid imaging using the gold-standard tracers [15O]water and [11C]PIB, respectively. Previous studies have explored the potential of [11C]PIB as both a functional and pathological biomarker, with early phases of the uptake reflecting blood flow and later retention reflecting amyloid burden. However, the reported studies have a number of shortcomings. Recently, in a small sample of subjects (N = 5 male subjects, 5 x 63 regions), we have found early phase PIB-based measures that were significantly related to global and regional CBF determined by quantitative [15O]water imaging. In this proposal, we plan to compare uptake measures derived from early phase, dynamic [11C]PIB imaging to global and regional cerebral blood flow (CBF) determined at rest with quantitative [15O]water in older participants (N = 24), representative of the population at-risk fo the development of AD (i.e., male and female subjects, 55 - 90 years old). To this end, we propose the following specific aim and hypothesis: Specific Aim: Determine the early phase global and regional [11C]PIB uptake and using this information in conjunction with relevant demographic information characterize the relationship between these measures and global and regional cerebral blood flow (CBF) as determined by quantitative [15O]water PET imaging. Hypothesis: Early phase [11C]PIB uptake, globally and regionally, is significantly related to global and regional measures of CBF, respectively. If a clinically-accessible metric, significantly related to CBF, can be established for [11C]PIB, then the stage is set for extension of this methodology to alternative amyloid agents with widespread clinical use potential, i.e., F-18 labeled radiotracers, and PIB-like kinetic behavior (e.g., [18F]NAV4694). If that goal is realized, a single agent in a single scan session could be used to define both the functional (CBF) and pathological (amyloid burden) status of a patient at-risk for vascular and/or Alzheimer's dementia.

描述（由申请人提供）：心血管风险因素（高血压、高脂血症、糖尿病、载脂蛋白e4基因型）和脑血管功能障碍与阿尔茨海默病（AD）发展风险增加相关。因此，发展阿尔茨海默病的病理评估应该理想地解决脑血管功能以及淀粉样蛋白病理。正电子发射断层扫描（PET）能够分别使用金标准示踪剂[15 O]水和[11 C] PIB通过脑血流和淀粉样蛋白成像来量化这两种属性。以前的研究已经探索了[11 C] PIB作为功能和病理生物标志物的潜力，早期摄取反映了血流，后期保留反映了淀粉样蛋白负荷。然而，报告的研究有一些缺点。最近，在一小部分受试者样本（N = 5例男性受试者，5 x 63个区域）中，我们发现早期基于PIB的测量与通过定量[15O]水成像确定的全球和区域CBF显著相关。在本提案中，我们计划将来自早期动态[11 C] PIB成像的摄取测量值与老年参与者（N = 24）在静息时用定量[15 O]水测定的全局和局部脑血流量（CBF）进行比较，老年参与者代表AD发展风险人群（即，男性和女性受试者，55 - 90岁）。为此，我们提出了以下具体目标和假设：具体目标：确定早期全球和区域[11 C] PIB摄取，并结合相关人口统计学信息使用该信息表征这些措施与全球和区域脑血流量（CBF）之间的关系，如定量[15 O]水PET成像所确定的。假设：全球和区域的早期[11 C] PIB摄取分别与全球和区域CBF措施显著相关。如果一个临床可及的指标， 与CBF相关，可以为[11 C] PIB建立，然后将该方法扩展到具有广泛临床应用潜力的替代淀粉样蛋白药物，即，F-18标记的放射性示踪剂和PIB样动力学行为（例如，[18F] NAV4694）。如果这一目标得以实现， 单次扫描中的单一药剂可用于确定处于血管性和/或阿尔茨海默氏痴呆风险中的患者的功能（CBF）和病理（淀粉样蛋白负荷）状态。