Binding Sites of a Positron Emission Tomography Imaging Agent in Alzheimer's β-Amyloid Fibrils Studied Using ¹⁹F Solid-State NMR.

ABSTRACT: Amyloid imaging by positron emission tomography (PET) is an important method for diagnosing neurodegenerative disorders such as Alzheimer's disease. Many ¹¹C- and ¹⁸F-labeled PET tracers show varying binding capacities, specificities, and affinities for their target proteins. The structural basis of these variations is poorly understood. Here we employ ¹⁹F and ¹³C solid-state NMR to investigate the binding sites of a PET ligand, flutemetamol, to the 40-residue Alzheimer's β-amyloid peptide (Aβ40). Analytical high-performance liquid chromatography and ¹⁹F NMR spectra show that flutemetamol binds the current Aβ40 fibril polymorph with a stoichiometry of one ligand per four to five peptides. Half of the ligands are tightly bound while the

SUBMITTER: Duan P 

PROVIDER: S-EPMC8855532 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature