Beta Amyloid Deposits Imaged with 18F-AZD4694 and Postmortem Histology

描述（由申请人提供）：Navidea Biopharmaceuticals正在开发18F-AZD 4694作为诊断成像剂，与PET扫描一起使用，以直接可视化活体患者大脑中的β淀粉样蛋白（A？）沉积物。痴呆症患者大脑中的A？沉积物可诊断为阿尔茨海默病。阿尔兹海默症患者的大脑中有丰富的A？沉积。目前，可视化或检测活体患者大脑中的A？沉积物非常具有挑战性或不可能。目前，只有在病人死亡后的尸检中才能观察到沉积物。能够想象A？在评估痴呆症患者时，A？沉积物将非常有用，因为患者大脑中缺乏A？沉积物排除了阿尔茨海默病的诊断。这很重要，因为虽然阿尔茨海默病是老年痴呆症最常见的原因，但也会发生许多其他类型的痴呆症。为痴呆症患者提供最高质量和最适当的护理需要正确确定其痴呆症的原因或类型。问题是，在所有被诊断为阿尔茨海默病的患者中，有15%-23%的人通过尸检发现他们的大脑中没有A？沉积物。这意味着这些患者被误诊为阿尔茨海默病，可能没有得到最好的治疗选择。能够想象A？如果在活体大脑中发现A？的沉积或缺失，就可以避免这些误诊，并大大提高痴呆症诊断的准确性。为了将18F-AZD 4694商业化并将该产品的益处带给痴呆症患者，Navidea正在提议一项涉及预期寿命相对较短的“生命末期”患者的研究。这项研究中大约三分之一的参与者将被诊断患有阿尔茨海默病。这些患者将在活着时使用18F-AZD 4694进行成像。在他们死后，他们的大脑将被收集起来，并检查A的存在和数量。拟议临床研究的目的是确定基于18F-AZD 4694成像预测的大脑中A <$沉积量与尸检时检测到的A <$沉积量之间的对应关系。临床前动物研究和来自先前完成的I期和II期临床试验的间接证据预测，通过成像检测到的A？与尸检检测到的A？之间的对应性将非常高。这项试验的成功完成对于确保FDA允许18F-AZD 4694开始上市至关重要，目的是排除阿尔茨海默病作为未患有阿尔茨海默病的痴呆患者的诊断。

DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals is developing 18F-AZD4694 as a diagnostic imaging agent to be used with PET scans to directly visualize beta amyloid (A¿) deposits in the brains of living patients. A¿ deposits in the brains of patients with dementia are diagnostic for Alzheimer's Disease. Al Alzheimer's Disease patients have abundant deposits of A¿ in their brains. Currently, it is very challenging or impossible to visualize or detect A¿ deposits in the brains of living patients. A¿ deposits are currently observed only at autopsy after a patient has died. Being able to visualize A¿ deposits would be extremely useful when evaluating patients with dementia because the absence of A¿ deposits in a patient's brain excludes a diagnosis of Alzheimer's Disease. This is important because, while Alzheimer's Disease is the most common cause of dementia in the elderly, many other types of dementia occur. Delivering the highest quality and most appropriate care to a patient with dementia requires that the cause or type of their dementia be correctly determined. The problem is that 15 percent - 23 percent of all patients given a diagnosis of Alzheimer's Disease in life tun out not to have A¿ deposits in their brains as determined by autopsy examinations. This means that these patients were misdiagnosed with Alzheimer's Disease and may not have received their best options for treatment. Being able to visualize A¿ deposits or the absence of A¿ in living brains would have avoided these misdiagnoses and dramatically improved the accuracy of dementia diagnoses. To commercialize 18F-AZD4694 and bring the benefits of this product to dementia patients, Navidea is proposing a study involving "end of life" patients with relatively short life expectancies. About a third of the enrolled participants in this study will have been diagnosed with Alzheimer's Disease. These patients will be imaged with 18F-AZD4694 while living. After their deaths, their brains will be collected and examined for the presence and amount of A¿ deposits. The goal of the proposed clinical study is to determine the correspondence between the amount of A¿ deposits predicted to be in the brains based on 18F-AZD4694 imaging and the actual amount of A¿ deposits detected at autopsy. Preclinical animal studies and indirect evidence from previously completed Phase I and Phase II clinical trial predict that the correspondence between A¿ detected by imaging and at autopsy will be very high. The successful completion of this trial is critical for securing allowance by the FDA to begi marketing 18F-AZD4694 for the purpose of excluding Alzheimer's Disease as a diagnosis for dementia patients who do not have Alzheimer's Disease.