Positron Emission Tomography Imaging of Fibrillar Parenchymal and Vascular Amyloid-β in TgCRND8 Mice

Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer's disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-beta (A beta) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A beta pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A beta antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer's disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A beta plaques and one antibody, M31, that targets vascular A beta. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and Cu-64 to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-A beta antibody targeting parenchymal A beta or M31, the antivascular A beta antibody. To confirm the validity of the noninvasive imaging of specific A beta pathology, brains were examined after imaging and showed clear evidence of binding to A beta plaques.