title: Quantification of the novel N-methyl-d-aspartate receptor ligand [11C]GMOM in man.
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.
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Thalia F
authors.initials: TF
authors.lastname: van der Doef
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands s.golla@vumc.nl.
authors.forename: Sandeep S V
authors.initials: SSV
authors.lastname: Golla
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Klein
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Oropeza-Seguias
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schuit
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Jobse
authors.affiliation: Department of Anesthesiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lothar A
authors.initials: LA
authors.lastname: Schwarte
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart N M
authors.initials: BNM
authors.lastname: van Berckel
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Glutamate; N-methyl-d-aspartate receptor; [11C]GMOM; kinetic modeling; positron emission tomography; quantitative imaging