[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] NAV 4694作为诊断成像剂，可用于可视化活体大脑中的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丰富的A斑块。非常需要开发更好的方法来识别那些在症状变得严重之前处于发展由阿尔茨海默病引起的痴呆症的高风险的个体。这一需求源于许多公司的广泛努力，为这种可怕的疾病开发新的和更好的疗法。目前正在研究90种这样的候选阿尔茨海默氏症疗法。由于这些候选药物中很大一部分的作用机制，在患者出现严重痴呆症之前给予它们可能最有效。这些新疗法的目的是防止或延缓他们的疾病发展为坦率的痴呆症。该提案所解决的问题是如何最好地识别这些患者。早在老年痴呆症患者发展为痴呆症之前的许多年，A斑块就开始出现在他们的大脑中。和其他人一样，我们也认识到，许多A斑块患者从未患上痴呆症。然而，A斑块是阿尔茨海默病病理学的指示，一旦A斑块患者开始经历认知能力下降，他们就有很高的风险进展为阿尔茨海默氏痴呆症。当患有阿尔茨海默病的人（即A斑块）首次出现认知症状时，他们的症状很小。这些人被称为轻度认知障碍（MCI）。然而，MCI除了阿尔茨海默病的病理学之外还有许多原因。患有MCI和与阿尔茨海默病相关的潜在病理学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治疗候选者，而患有其他病理学的MCI患者则不会。在拟议的研究中，MCI患者将使用正电子发射断层扫描（PET）使用[18 F] NAV 4694进行成像，以识别大脑中有A斑块的个体。然后，研究中的所有参与者将被随访至少18个月，以确定哪些人会发展为坦率的阿尔茨海默氏痴呆症。预计进展到明显阿尔茨海默氏痴呆的所有参与者将具有通过[18 F] NAV 4694可视化的A斑块的证据，而缺乏A斑块的参与者中没有一个将进展到定义的阿尔茨海默氏痴呆。因此，将获得表明[18F] NAV 4694成像可用于鉴定所有MCI患者中处于发展阿尔茨海默氏痴呆症的高风险的部分的证据。其他公司也在开发A显像剂;然而，Navidea Biopharmaceuticals认为，根据其最近直接对比[18 F] NAV 4694与[18 F]PIB的临床数据，[18 F] NAV 4694与其竞争对手相比具有上级性能特征，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.