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，对发展中的阿尔茨海默病病理的评估应该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）能够通过脑血流和淀粉样蛋白成像来量化这两个属性，分别使用金标准示踪剂[15O]水和[11C]PIB。先前的研究已经探索了[11C]PIB作为功能和病理生物标志物的潜力，早期摄取反映血流量，后期保留反映淀粉样蛋白负担。然而，报告的研究有一些不足之处。最近，在一个小样本受试者（N = 5名男性受试者，5 x 63个区域）中，我们发现基于pib的早期测量与定量[15O]水成像确定的全球和区域CBF显著相关。在本提案中，我们计划比较老年参与者（N = 24）的早期动态[11C]PIB成像与静止时定量[15O]水测定的全球和区域脑血流量（CBF）的摄取测量，这些参与者代表了AD发展风险人群（即55 - 90岁的男性和女性受试者）。为此，我们提出以下具体目标和假设：具体目标：确定早期全球和区域[11C]PIB摄取，并结合相关人口统计学信息，表征这些措施与定量[15O]水PET成像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[11C]PIB吸收分别与全球和区域CBF测量显著相关。如果一个临床可及的指标，显著

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.