Abstract

[18F]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 [18F]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, [18F]D15FSP, and compared it with N-methyl-deuterated [18F]D3FSP and nondeuterated [18F]AV-45. D15FSP displayed excellent binding affinity (K i = 7.52 nM) to Aβ aggregates. In vitro autoradiography of [18F]D15FSP, [18F]D3FSP, and [18F]AV-45 showed excellent binding to Aβ plaques in human AD brain sections. Biodistribution studies displayed lower bone uptake at 120 min for [18F]D15FSP compared to that for [18F]D3FSP and [18F]AV-45 (1.44 vs 4.23 and 4.03%ID/g, respectively). As the highly deuterated [18F]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.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.