[18F]NAV4694 Imaging to Identify MCI Patients at Risk for Alzheimer's Dementia

描述（由申请人提供）：Navidea Biopharmaceuticals正在开发[18F]NAV4694作为诊断显像剂，可用于可视化活体个体大脑中的β -淀粉样蛋白(a)斑块。阿尔茨海默病是痴呆症的主要原因。所有由阿尔茨海默病引起的痴呆患者的大脑中都有大量的A斑块。有必要开发更好的方法，在阿尔茨海默病引起的痴呆症症状变得严重之前，识别出那些有高风险的人。这种需求源于许多公司为开发新的更好的治疗这种可怕疾病的方法所做的广泛努力。目前有90种阿尔茨海默病候选疗法正在研究中。由于这些候选药物的很大一部分的作用机制，它们可能是最有效的给病人之前，他们有明显的痴呆。这些新疗法的目的是防止或延缓他们的疾病发展到痴呆。该提案解决的问题是如何最好地识别这些患者。阿尔茨海默氏症患者的大脑中早在他们发展成痴呆症的许多年前就开始出现斑块。我们和其他人一样认识到，许多有A斑块的人永远不会患上痴呆症。然而，A斑块是阿尔茨海默病的病理指标，一旦患有A斑块的患者开始出现认知能力下降，他们就有很高的风险发展为阿尔茨海默病痴呆症。当患有阿尔茨海默病病理（即A斑块）的人首次出现认知症状时，他们的症状是最小的。这些人被称为轻度认知障碍（MCI）。然而，除了阿尔茨海默病之外，MCI可能有许多原因。患有MCI和与阿尔茨海默氏症相关的潜在病理的患者将是目前正在开发的新的阿尔茨海默病修饰疗法的候选者，而患有其他病理的MCI患者则不会。在本研究中，MCI患者将使用[18F]NAV4694进行正电子发射断层扫描（PET）成像，以识别大脑中有A斑块的个体。所有参与研究的人都将被随访至少18个月，以确定哪些人会发展为阿尔茨海默氏痴呆症。预计所有进展为阿尔茨海默氏痴呆症的参与者都有A斑块的证据，这是由[18F]NAV4694可视化的，而没有A斑块的参与者将进展为阿尔茨海默氏痴呆症。因此，将获得证据表明[18F]NAV4694成像可用于识别所有MCI患者中发生阿尔茨海默氏痴呆症的高风险部分。其他公司也在开发A显像剂；然而，Navidea Biopharmaceuticals认为，基于其最近的临床数据直接对比[18F]NAV4694与[18F]PIB， [18F]NAV4694与竞争对手相比优越的性能特征将使其成为该应用的首选显像剂。

DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals is developing [18F]NAV4694 as a diagnostic imaging agent that can be used to visualize beta-amyloid (A) plaques in the brains of living individuals. Alzheimer's disease is the leading cause of dementia. All patients with dementia caused by Alzheimer's disease have abundant A plaques in their brains. There is a great need to develop better means to identify individuals who are at high risk of developing dementia caused by Alzheimer's disease before their symptoms become severe. This need has arisen from the extensive efforts of many companies to develop new and better therapies for this dreaded disease. Ninety such candidate Alzheimer's therapies are currently under investigation. Due to the mechanisms of action of a large portion of these drug candidates, they are likely to be most effective when given to patients before they have significant dementia. The intent of these new therapies will be to prevent or delay the progression of their illnesses to frank dementia. The problem addressed by this proposal is how to best indentify these patients. A plaques begin to appear in the brains of Alzheimer's patients many years before they develop dementia. We recognize, as others, many individuals with A plaques never develop dementia. However, A plaques are indicative of Alzheimer's pathology, and once a patient with A plaques begins to experience cognitive decline, they are at high risk of progression to Alzheimer's dementia. When people with Alzheimer's pathology (i.e. A plaques) first experience cognitive symptoms, their symptoms are minimal. Such people are said to have Mild Cognitive Impairment (MCI). However, MCI can have many causes besides Alzheimer's pathology. Patients with MCI and the underlying pathology associated with Alzheimer's would be candidates for treatment with the new Alzheimer's disease modifying therapies currently under development, while MCI patients with other pathologies would not. In the proposed study, patients with MCI will be imaged with [18F]NAV4694 using positron emission tomography (PET) to identify those individuals with A plaques in their brains. All participants in the study will then be followed for at least 18 months to determine which individuals progress to frank Alzheimer's dementia. It is expected that all participants that progress to frank Alzheimer's dementia will have had evidence of A plaques that were visualized by [18F]NAV4694, while none of the participants lacking A plaques will have progressed to defined Alzheimer's dementia. Thereby, evidence will have been obtained indicating that [18F]NAV4694 imaging could be used to identify the portion of all MCI patients that is at high risk for developing Alzheimer's dementia. Other firms are also developing A imaging agents; however, Navidea Biopharmaceuticals believes, based on its recent clinical data directly contrasting [18F]NAV4694 vs. [18F]PIB, that the superior performance characteristics of [18F]NAV4694 compared to its competitors will make it the preferred imaging agent for this application.