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

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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.