Quantification of the Novel N-methyl-d-aspartate Receptor Ligand [11C]GMOM in Man.

[C-11] GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N'-(3-[C-11] methoxy-phenyl)-N'-methylguanidine) is a PET ligand that binds to the N-methyl-D-aspartate receptor with high specificity and affinity. The purpose of this first in human study was to evaluate kinetics of [C-11] GMOM in the healthy human brain and to identify the optimal pharmacokinetic model for quantifying these kinetics, both before and after a pharmacological dose of S-ketamine. Dynamic 90 min [C-11] GMOM PET scans were obtained from 10 subjects. In six of the 10 subjects, a second PET scan was performed following an S-ketamine challenge. Metabolite corrected plasma input functions were obtained for all scans. Regional time activity curves were fitted to various single-and two-tissue compartment models. Best fits were obtained using a two-tissue irreversible model with blood volume parameter. The highest net influx rate (Ki) of [C-11] GMOM was observed in regions with high N-methyl-D-aspartate receptor density, such as hippocampus and thalamus. A significant reduction in the Ki was observed for the entire brain after administration of ketamine, suggesting specific binding to the N-methyl-D-aspartate receptors. This initial study suggests that the [C-11] GMOM could be used for quantification of N-methyl-D-aspartate receptors.