Imaging of antibody therapeutics in mouse models of Alzheimer's Disease

阿尔茨海默病(AD)是痴呆症最常见的原因，会导致虚弱的记忆丧失，最终导致死亡。这种疾病的一个特征是大脑中淀粉样β斑块的积累，导致神经原纤维缠结和突触密度下降。人们认为，防止淀粉样β蛋白在大脑中积聚是必要的，以防止淀粉样斑块的发展，从而避免这些斑块导致的神经功能退化。Cangene是一家总部位于温尼伯的生物技术公司，该公司已经开发出抗体试剂，当注射到小鼠或大鼠大脑中时，可以与淀粉样β蛋白结合。这些治疗剂进一步发展的一个关键挑战是了解有多少抗体穿过血脑屏障(BBB)，从而具有结合大脑中淀粉样β蛋白的能力。在这项NSERC Engage项目中，马尼托巴大学的研究人员将与Cangene合作，用荧光和放射性染料标记新开发的抗体，然后在阿尔茨海默病小鼠模型中使用非侵入性荧光和正电子发射断层扫描(PET)成像测量它们在全身注射后在大脑中的摄取。该项目的成果将是开发新的成像方案和分析技术，使小鼠大脑中抗体摄取的跨模式量化成为可能。这些跨平台的量化方法将允许Cangene在未来使用这些体内成像方法来快速评估新的抗体同种类型，从而减少识别有前景的新治疗药物所需的时间。

Alzheimer's Disease (AD) is the most common cause of dementia, leading to debilitating memory loss and ultimately death. A hallmark of the disease is the accumulation of amyloid beta plaques in the brain, leading to neurofibrillary tangles and decreased synaptic density. It is thought that preventing the accumulation of amyloid beta in the brain is necessary to prevent the development of amyloid plaques and therefore avoid the degradation in neurological function that these plaques cause. Cangene is a Winnipeg-based biotechnology company that has developed antibody agents that can bind to amyloid beta when injected into the mouse or rat brain. A key challenge to the further development of these therapeutic agents is an understanding of how much of the antibody crosses the blood brain barrier (BBB) and thus has the ability to bind amyloid beta in the brain. In this NSERC Engage project, researchers at the University of Manitoba, in collaboration with Cangene, will label the newly developed antibodies with both fluorescent and radioactive dyes and then measure their uptake in the brain following systemic injection using non-invasive fluorescence and positron emission tomography (PET) imaging in mouse models of AD. The outcome of this project will be the development of new imaging protocols and analysis techniques that enable cross-modality quantification of antibody uptake in the mouse brain. These cross-platform quantification methods will allow Cangene to use these in vivo imaging methods in the future for rapid evaluation of new antibody isotypes, reducing the time required for identification of promising new therapeutic agents.