%0 Journal Article
%A Hoffmann, Chris
%A Evcüman, Sibel
%A Neumaier, Felix
%A Zlatopolskiy, Boris D.
%A Humpert, Swen
%A Bier, Dirk
%A Holschbach, Marcus
%A Schulze, Annette
%A Endepols, Heike
%A Neumaier, Bernd
%T [18F]ALX5406: A Brain-Penetrating Prodrug for GlyT1-Specific PET Imaging
%J ACS chemical neuroscience
%V 12
%N 18
%@ 1948-7193
%C Washington, DC
%I ACS Publ.
%M FZJ-2021-03517
%P 3335 - 3346
%D 2021
%X Selective inhibition of glycine transporter 1 (GlyT1) has emerged as a potential approach to alleviate N-methyl-D-aspartate receptor (NMDAR) hypofunction in patients with schizophrenia and cognitive decline. ALX5407 is a potent and selective inhibitor of GlyT1 derived from the metabolic intermediate sarcosine (N-methylglycine) that showed antipsychotic potential in a number of animal models. Whereas clinical application of ALX5407 is limited by adverse effects on motor performance and respiratoryfunction, a suitably radiolabeled drug could represent a promising PET tracer for the visualization of GlyT1 in the brain. Herein, [18F]ALX5407 and the corresponding methyl ester, [18F]ALX5406, were prepared by alcoholenhanced copper mediated radiofluorination and studied in vitro in rat brain slices and in vivo in normal rats. [18F]ALX5407 demonstrated accumulation consistent with the distribution of GlyT1 in in vitro autoradiographic studies but no brain uptake in μPET experiments in naıv̈ e rats. In contrast, the methyl ester [18F]ALX5406 rapidly entered the brain and was enzymatically transformed into [18F]ALX5407, resulting in a regional accumulation pattern consistent with GlyT1 specific binding. We conclude that [18F]ALX5406 is a promising and easily accessible PET probe for preclinical in vivo imaging of GlyT1 in the brain.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 34449193
%U <Go to ISI:>//WOS:000697282400006
%R 10.1021/acschemneuro.1c00284
%U https://juser.fz-juelich.de/record/894996