TY - JOUR
T1 - Quantification of the novel N-methyl-D-aspartate receptor ligand [C-11] GMOM in man
AU - van der Doef, Thalia F.
AU - Golla, Sandeep S. V.
AU - Klein, Pieter J.
AU - Oropeza-Seguias, Gisela M.
AU - Schuit, Robert C.
AU - Metaxas, Athanasios
AU - Jobse, Ellen
AU - Schwarte, Lothar A.
AU - Windhorst, Albert D.
AU - Lammertsma, Adriaan A.
AU - van Berckel, Bart N. M.
AU - Boellaard, Ronald
PY - 2016/6
Y1 - 2016/6
N2 - [11C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N′-(3-[11C]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 [11C]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 [11C]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 [11C]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 [11C]GMOM could be used for quantification of N-methyl-d-aspartate receptors.
AB - [11C]GMOM (carbon-11 labeled N-(2-chloro-5-thiomethylphenyl)-N′-(3-[11C]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 [11C]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 [11C]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 [11C]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 [11C]GMOM could be used for quantification of N-methyl-d-aspartate receptors.
KW - Glutamate
KW - N-methyl-D-aspartate receptor
KW - [C-11] GMOM
KW - kinetic modeling
KW - positron emission tomography
KW - quantitative imaging
U2 - https://doi.org/10.1177/0271678X15608391
DO - https://doi.org/10.1177/0271678X15608391
M3 - Article
C2 - 26661185
SN - 0271-678X
VL - 36
SP - 1111
EP - 1121
JO - Journal of cerebral blood flow and metabolism
JF - Journal of cerebral blood flow and metabolism
IS - 6
ER -