A New Highly Deuterated [18F]AV-45, [18F]D15FSP, for Imaging β-Amyloid Plaques in the Brain
Year: 2021
Type: article
Abstract: [ 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.
Source: ACS Medicinal Chemistry Letters
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3174284341