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    Characterization of PET tracer Flutemetamol (GE-067) binding to Aβ1-40 fibrils

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    abstract (74.24Kb)
    Date
    2022-04-29
    Author
    Wijegunawardena, Gayani
    Duan, Pu
    Kelly, J. Chen
    Aurelio, J. Dregni
    Harrison, K. Wang
    Advisor
    Hong, Mei; Wu, Haifan
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    Citation
    Wijegunawardena, G.; Duan, P.; |Kelly, J. C.; Aurelio, J. D.; Harrison, K. W. 2022. Characterization of PET tracer Flutemetamol (GE-067) binding to Aβ1-40 fibrils -- In Proceedings: 18th Annual Symposium on Graduate Research and Scholarly Projects. Wichita, KS: Wichita State University
    Abstract
    Alzheimer's disease (AD) is a neurological disorder and the most common cause of dementia. One of the major pathological hallmarks of AD is the deposition of amyloid beta peptide (Aβ) into plaques. In the past decade, Positron Emission Tomography (PET) has been used to detect plaques in patients for diagnosis. Although several PET tracers including Flutemetamol (GE-067) have been developed and approved by FDA, their interaction with Aβ fibrils at molecular level is not fully understood. In this study, we aim to characterize the binding of GE-067 to Aβ1-40 fibrils in detail. We developed a binding assay based on HPLC quantification. Using Aβ1-40 fibrils prepared in vitro, we determined the binding stoichiometry of 1:4.6 (GE-067 to Aβ1-40 as a monomer). In collaboration with Prof. Hong, solid-state NMR and molecular docking were used to determine the binding sites of flutemetamol using $^{13}C$, $^{15}N$-labeled Aβ1-40. Our data support multiple binding sites for flutemetamol in Aβ1-40 fibrils. We believe our binding study will guide the effort to further optimize these amyloid PET tracers for higher affinity and selectivity.
    Description
    Presented to the 18th Annual Symposium on Graduate Research and Scholarly Projects (GRASP) held at the Rhatigan Student Center, Wichita State University, April 29, 2022

    Research completed in the Department of Chemistry and Biochemistry, Fairmount College of Liberal Arts and Sciences
    URI
    https://soar.wichita.edu/handle/10057/23529
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    • CHEM Graduate Student Conference Papers
    • Proceedings 2022: 18th Annual Symposium on Graduate Research and Scholarly Projects

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