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A New Highly Deuterated [F]AV-45, [F]D15FSP, for Imaging β-Amyloid Plaques in the Brain. | LitMetric
[F]AV-45 (florbetapir f18, Amyvid) is an FDA-approved PET imaging agent targeting Aβ plaques in the brain for diagnosis of Alzheimer's disease (AD). Its metabolites led to a high background in the brain and large bone uptake of [F]F, produced from dealkylation of the PEG chain. To slow down the in vivo metabolism, we report the design, synthesis, and evaluation of a highly deuterated derivative, [F]D15FSP, and compared it with -methyl-deuterated [F]D3FSP and nondeuterated [F]AV-45. D15FSP displayed excellent binding affinity ( = 7.52 nM) to Aβ aggregates. In vitro autoradiography of [F]D15FSP, [F]D3FSP, and [F]AV-45 showed excellent binding to Aβ plaques in human AD brain sections. Biodistribution studies displayed lower bone uptake at 120 min for [F]D15FSP compared to that for [F]D3FSP and [F]AV-45 (1.44 vs 4.23 and 4.03%ID/g, respectively). As the highly deuterated [F]D15FSP displayed excellent Aβ binding affinity, high initial brain penetration, and lower bone retention, it might be suitable for PET imaging in detecting Aβ plaques.
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