[18F]ALX5406: A brain-penetrant pro-drug for GlyT1-specific PET imaging

Abstract

To visualize glycine transporter 1 (GlyT1) in the brain using PET imaging, the compounds [¹⁸F]ALX5407 and its corresponding methyl ester, [¹⁸F]ALX5406, were prepared via alcohol-enhanced copper-mediated radiofluorination and subjected to a preclinical evaluation. While [¹⁸F]ALX5407 demonstrated accumulation consistent with the GlyT1 distribution in rat brain slices, it showed no brain uptake in healthy rats. In contrast, the methyl ester [¹⁸F]ALX5406 rapidly entered the brain, where it was enzymatically converted into [¹⁸F]ALX5407, resulting in a regional accumulation pattern consistent with GlyT1-specific binding. Therefore, [¹⁸F]ALX5406 represents a promising PET tracer for preclinical in vivo imaging of GlyT1 in the brain.

Hoffmann, C.; Evcüman, S.; Neumaier, F.; Zlatopolskiy, B.; Humpert, S.; Bier, D.; Holschbach, M.; Schulze, A.; Endepols, H.; Neumaier, B.

[¹⁸F]ALX5406: A Brain-Penetrating Prodrug for GlyT1-Specific PET Imaging

ACS chemical neuroscience 2021, 12 (18), 3335-3346.