TY  - JOUR
AU  - Hoffmann, Chris
AU  - Evcüman, Sibel
AU  - Neumaier, Felix
AU  - Zlatopolskiy, Boris D.
AU  - Humpert, Swen
AU  - Bier, Dirk
AU  - Holschbach, Marcus
AU  - Schulze, Annette
AU  - Endepols, Heike
AU  - Neumaier, Bernd
TI  - [18F]ALX5406: A Brain-Penetrating Prodrug for GlyT1-Specific PET Imaging
JO  - ACS chemical neuroscience
VL  - 12
IS  - 18
SN  - 1948-7193
CY  - Washington, DC
PB  - ACS Publ.
M1  - FZJ-2021-03517
SP  - 3335 - 3346
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34449193
UR  - <Go to ISI:>//WOS:000697282400006
DO  - DOI:10.1021/acschemneuro.1c00284
UR  - https://juser.fz-juelich.de/record/894996
ER  -