SPECT Imaging of Abeta Plaques in Brain

大脑 Abeta 斑块的 SPECT 成像

• 批准号: 6930608
• 负责人: MEI-PING tien KUNG
• 金额: $ 23.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930608
• 关键词: Alzheimer' s disease; amyloid proteins; autoradiography; bioimaging /biomedical imaging; biomaterial development /preparation; biomaterial evaluation; brain disorder diagnosis; brain imaging /visualization /scanning; chemical binding; chemical synthesis; contrast media; early diagnosis; genetically modified animals; histopathology; iodination; laboratory mouse; ligands; neuritic plaques; radiation dosage; radiography; radionuclides; reagent /indicator; single photon emission computed tomography; stilbenes; toxicology

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a neurodegenerative disease of the brain characterized by dementia, cognitive impairment and memory loss. Formation and accumulation of aggregates of &-amyloid (AB) peptides in the brain are critical factors contributing to the development and progression of AD. Currently, early appraisal of clinical symptoms for diagnosis of AD is often difficult and unreliable. Therefore, there is an urgent need for in vivo imaging agents, which can specifically demonstrate the location and density of amyloid plaques in the brain. The objective of this project is to develop potential 1-123 labeled diagnostic imaging agents specific for detection of AB plaques. Recent advances in developing tracers for binding A13 plaques suggest that there are specific and saturable binding sites on the aggregates of At3 that can be selectively labeled and imaged in vivo. The proposed agents are derivatives of stilbenes containing a p-MezN-, -SH, -SMe, -0Me or -OH group on one of the benzene rings, while radioactive iodine can be attached to the other benzene ring without affecting the binding affinity. They are simple, relatively small, neutral and lipophilic. On the basis of their exquisitely high binding affinity to At3140 aggregates (Ki at the range of 0.1-40 nM), they are suitable candidates as A&-plaque-selective imaging agents. They also showed ability to penetrate the intact blood-brain barrier, an essential pre-requisite for a useful plaque-imaging agent. The proposed synthesis and methodology provide a framework to test the hypothesis that small probes can be used to detect At3 plaques in vivo. The proposed compounds are innovative and carefully crafted to meet the stringent requirements for t3-amyloid imaging agents. Together with the compelling preliminary data presented in this project we believe that At3 plaque-selective imaging agents can be successfully developed. The At3-plaque-specific imaging agents will be useful for early detection or monitoring the progression and effectiveness of treatment of AD.

描述（由申请人提供）：阿尔茨海默氏病（AD）是一种以痴呆，认知障碍和记忆力丧失为特征的大脑的神经退行性疾病。大脑中＆淀粉样蛋白（AB）肽聚集体的形成和积累是导致AD发展和进展的关键因素。当前，早期对AD诊断的临床症状的评估通常很困难且不可靠。因此，迫切需要体内成像剂，这可以特异性地证明大脑中淀粉样蛋白斑块的位置和密度。该项目的目的是开发潜在的1-123标记的诊断成像剂，特异性用于检测AB斑块。开发用于结合A13斑块的示踪剂的最新进展表明，AT3的聚集体上有特定且饱和的结合位点，可以在体内选择性地标记和成像。所提出的药物是含有p -mezn-，-sh，-sme，-0me或-oH基团的二苯甲酸的衍生物，而放射性碘可以连接到其他苯环，而不会影响结合亲和力。它们很简单，相对较小，中性和亲脂性。根据它们与AT3140骨料（0.1-40 nm范围内的Ki）的精确结合亲和力，它们是合适的候选物作为A＆plaquque-plaque选择性成像剂。它们还显示出穿透完整的血脑屏障的能力，这是有用的斑块成像剂的必要前提。所提出的合成和方法提供了一个框架来检验以下假设：小探针可用于检测体内的AT3斑块。所提出的化合物具有创新性和精心制作，以满足T3-淀粉样蛋白成像剂的严格要求。加上该项目中提供的引人注目的初步数据，我们认为可以成功地开发AT3斑块选择性成像剂。 AT3-Plaque特异性成像剂将有助于早期检测或监测AD治疗的进展和有效性。