Positron Emission Tomography Imaging of Fibrillar Parenchymal and Vascular Amyloid-尾 in TgCRND8 Mice
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- 作者：Daniel McLean ; Michael J. Cooke ; Ricardo Albay ; III ; Charles Glabe ; Molly S. Shoichet
- 刊名：ACS Chemical Neuroscience
- 出版年：2013
- 出版时间：April 17, 2013
- 年：2013
- 卷：4
- 期：4
- 页码：613-623
- 全文大小：555K
- 年卷期：v.4,no.4(April 17, 2013)
- ISSN：1948-7193
文摘
Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer鈥檚 disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-尾 (A尾) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A尾 pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A尾 antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer鈥檚 disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A尾 plaques and one antibody, M31, that targets vascular A尾. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and 64Cu 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尾 antibody targeting parenchymal A尾 or M31, the antivascular A尾 antibody. To confirm the validity of the noninvasive imaging of specific A尾 pathology, brains were examined after imaging and showed clear evidence of binding to A尾 plaques.