Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: van der Doef, Thalia F; Golla, Sandeep SV; Klein, Pieter J; Oropeza-Seguias, Gisela M; Schuit, Robert C; Metaxas, Athanasios; Jobse, Ellen; Schwarte, Lothar A; Windhorst, Albert D; Lammertsma, Adriaan A; van Berckel, Bart NM; Boellaard, Ronald
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 36:Issue 6(2016)
• Page Start: 1111
• Page End: 1121
• Publication Date: 2016-06
• Subjects: Glutamate -- [11C]GMOM -- kinetic modeling -- N-methyl-d-aspartate receptor -- positron emission tomography -- quantitative imaging; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X15608391
• Languages: English
• ISSNs: 0271-678X

Abstract

[ 11 C]GMOM (carbon-11 labeled N -(2-chloro-5-thiomethylphenyl)- N ′-(3-[ 11 C]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 [ 11 C]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 [ 11 C]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 [ 11 C]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 [ 11 C]GMOM could be used for quantification of N -methyl-d -aspartate receptors.