A New Highly Deuterated [ 18 F]AV-45, [ 18 F]D15FSP, for Imaging β-Amyloid Plaques in the Brain.

[ ¹⁸ 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 [ ¹⁸ 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, [ ¹⁸ F]D15FSP, and compared it with N -methyl-deuterated [ ¹⁸ F]D3FSP and nondeuterated [ ¹⁸ F]AV-45. D15FSP displayed excellent binding affinity ( K _i = 7.52 nM) to Aβ aggregates. In vitro autoradiography of [ ¹⁸ F]D15FSP, [ ¹⁸ F]D3FSP, and [ ¹⁸ F]AV-45 showed excellent binding to Aβ plaques in human AD brain sections. Biodistribution studies displayed lower bone uptake at 120 min for [ ¹⁸ F]D15FSP compared to that for [ ¹⁸ F]D3FSP and [ ¹⁸ F]AV-45 (1.44 vs 4.23 and 4.03%ID/g, respectively). As the highly deuterated [ ¹⁸ 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.
Competing Interests: The authors declare no competing financial interest.
(© 2021 American Chemical Society.)