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

描述(由申请人提供)：心血管危险因素(高血压、高脂血症、糖尿病、载脂蛋白e4基因)和脑血管功能障碍与阿尔茨海默病(AD)的发展风险增加有关。因此，对阿尔茨海默病病理发展的评估应该理想地同时考虑脑血管功能和淀粉样蛋白病理。正电子发射断层扫描(PET)能够通过分别使用金标准示踪剂[150]水和[11C]PIB的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[11C]PIB作为功能和病理生物标记物的潜力，早期摄取反映血流，后期滞留反映淀粉样蛋白负荷。然而，已报道的研究有一些不足之处。最近，在一小部分受试者(N=5名男性受试者，5×63个区域)中，我们发现基于PIB的早期测量与定量[150]水成像确定的全球和区域CBF显著相关。在这项建议中，我们计划将早期动态的[11C]PIB显像所得出的摄取指标与静息状态下用定量[150]水测定的全局和局部脑血流量(CBF)进行比较，老年受试者(N=24)是AD高危人群的代表(即55-90岁的男性和女性受试者)。为此，我们提出了以下特定的目标和假设：特定的目标：确定早期阶段全球和区域的[11C]PIB摄取，并结合相关的人口统计学信息来表征这些测量与定量[150]水PET成像所确定的全球和区域脑血流量(CBF)之间的关系。假设：全球和区域的早期阶段[11C]PIB摄取分别与全球和区域的CBF指标显著相关。如果一个临床可及的指标，显著 与CBF相关的，可以为[11C]PIB建立，然后为将该方法扩展到具有广泛临床应用潜力的替代淀粉样剂，即F-18标记的放射性示踪剂和PIB样动力学行为(例如，[18F]NAV4694)奠定了基础。如果这个目标实现了， 单一扫描过程中的单一试剂可用于确定有血管性和/或阿尔茨海默氏症风险的患者的功能(CBF)和病理(淀粉样蛋白负担)状态。

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.