TY - JOUR
T1 - Measurement of glycine binding site of N-methyl-D-asparate receptors in living human brain using 4-acetoxy derivative of L-703,717, 4-acetoxy-7-chloro- 3-[3-(4-[11C] methoxybenzyl) phenyl]-2(1H)-quinolone (AcL703) with positron emission tomography
AU - Matsumoto, Ryohei
AU - Haradahira, Terushi
AU - Ito, Hiroshi
AU - Fujimura, Yota
AU - Seki, Chie
AU - Ikoma, Yoko
AU - Maeda, Jun
AU - Arakawa, Ryosuke
AU - Takano, Akihiro
AU - Takahashi, Hidehiko
AU - Higuchi, Makoto
AU - Suzuki, Kazutoshi
AU - Fukui, Kenji
AU - Suhara, Tetsuya
PY - 2007/10
Y1 - 2007/10
N2 - N-methyl-D-aspartate (NMDA) receptors are of major interest in brain functions and neuropsychiatric disorders. However, at present there are few suitable radioligands for in vivo imaging of NMDA receptors. 7-Choloro-4-hydroxy-3-[3-(4-methoxybenzyl) phenyl]-2(1H)-quinolone (L-703,717) is one of the potent ligands for the glycine-binding site of NMDA receptors. 4-Acetoxy derivative of L-703,717 (AcL703) is a candidate, as a positron emission tomography (PET) ligand for NMDA receptors, because of its better permeability at the blood-brain barrier compared with L-703,717. After intravenous injection of 624-851 MBq of [11C]AcL703, dynamic PET scan was performed on six healthy males for 90 min. Regions-of-interest were located on the cerebral cortices, cerebellar cortex, and cerebral white matter. The binding potential (BP) was calculated from the ratio of the area under the curve (AUC) of radioactivities from 40 to 90 min in the target region to that in white matter. Regional radioactivities reached close to equilibrium in all regions after about 40 min postinjection. Regional brain uptake of [ 11C]AcL703 at 40 min after injection was 0.00028-0.00065% of the injected dose/milliliter. Radioactivity concentration of [11C]AcL703 was highest in the cerebellar cortex and lowest in white matter. AUC in the cerebellar cortex was higher than those of cerebral cortices, thalamus, striatum, and white matter. BP in the cerebellar cortex was twofold higher than in the cerebral cortices (cerebellar cortex: BP = 2.20 ± 0.72; cerebral cortices: BP = 1.05 ± 0.45). Despite the low brain uptake of [ 11C]AcL703, regional distributions were in good agreement with our previous studies of rodents. This indicates the possibility of in vivo evaluation of NMDA receptors using PET with [11C]AcL703 in living human brain.
AB - N-methyl-D-aspartate (NMDA) receptors are of major interest in brain functions and neuropsychiatric disorders. However, at present there are few suitable radioligands for in vivo imaging of NMDA receptors. 7-Choloro-4-hydroxy-3-[3-(4-methoxybenzyl) phenyl]-2(1H)-quinolone (L-703,717) is one of the potent ligands for the glycine-binding site of NMDA receptors. 4-Acetoxy derivative of L-703,717 (AcL703) is a candidate, as a positron emission tomography (PET) ligand for NMDA receptors, because of its better permeability at the blood-brain barrier compared with L-703,717. After intravenous injection of 624-851 MBq of [11C]AcL703, dynamic PET scan was performed on six healthy males for 90 min. Regions-of-interest were located on the cerebral cortices, cerebellar cortex, and cerebral white matter. The binding potential (BP) was calculated from the ratio of the area under the curve (AUC) of radioactivities from 40 to 90 min in the target region to that in white matter. Regional radioactivities reached close to equilibrium in all regions after about 40 min postinjection. Regional brain uptake of [ 11C]AcL703 at 40 min after injection was 0.00028-0.00065% of the injected dose/milliliter. Radioactivity concentration of [11C]AcL703 was highest in the cerebellar cortex and lowest in white matter. AUC in the cerebellar cortex was higher than those of cerebral cortices, thalamus, striatum, and white matter. BP in the cerebellar cortex was twofold higher than in the cerebral cortices (cerebellar cortex: BP = 2.20 ± 0.72; cerebral cortices: BP = 1.05 ± 0.45). Despite the low brain uptake of [ 11C]AcL703, regional distributions were in good agreement with our previous studies of rodents. This indicates the possibility of in vivo evaluation of NMDA receptors using PET with [11C]AcL703 in living human brain.
UR - http://www.scopus.com/inward/record.url?scp=34548245979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548245979&partnerID=8YFLogxK
U2 - 10.1002/syn.20415
DO - 10.1002/syn.20415
M3 - Article
C2 - 17598152
AN - SCOPUS:34548245979
SN - 0887-4476
VL - 61
SP - 795
EP - 800
JO - Synapse
JF - Synapse
IS - 10
ER -
