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
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
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DOI：
10.1002/syn.20415
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发表时间：
2007-10
期刊：
影响因子：
2.3
通讯作者：
Ryohei Matsumoto;T. Haradahira;Hiroshi Ito;Y. Fujimura;C. Seki;Y. Ikoma;J. Maeda;R. Arakawa;A. Takano;Hidehiko Takahashi;M. Higuchi;Kazutoshi Suzuki;K. Fukui;T. Suhara
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文献类型：
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作者：
Ryohei Matsumoto;T. Haradahira;Hiroshi Ito;Y. Fujimura;C. Seki;Y. Ikoma;J. Maeda;R. Arakawa;A. Takano;Hidehiko Takahashi;M. Higuchi;Kazutoshi Suzuki;K. Fukui;T. Suhara
N-甲基-D-天冬氨酸（NMDA）受体在脑功能和神经精神疾病中具有重要意义。然而，目前很少有合适的放射性配体用于NMDA受体的体内成像。7-氯-4-羟基-3-[3-（4-甲氧基苄基）苯基]-2（1H）-喹诺酮（L-703，717）是NMDA受体甘氨酸结合位点的有效配体之一。L-703，717的4-乙酰氧基衍生物（AcL 703）是NMDA受体的正电子发射断层扫描（PET）配体的候选者，因为与L-703，717相比，其在血脑屏障上的渗透性更好。静脉注射624-851 MBq [11 C] AcL 703后，对6名健康男性进行动态PET扫描90 min。感兴趣区域位于大脑皮质、小脑皮质和大脑白色物质。根据靶区40 - 90 min放射性曲线下面积（AUC）与白色物质中放射性曲线下面积的比值计算结合电位（BP）。注射后约40分钟后，所有区域的局部放射性达到接近平衡。注射后40 min时[11 C] AcL 703的局部脑摄取为注射剂量的0.00028-0.00065%/ml。[11 C] AcL 703的放射性浓度在小脑皮质中最高，在白色物质中最低。小脑皮质的AUC高于大脑皮质、丘脑、纹状体和白色物质的AUC。小脑皮质的血压是大脑皮质的2倍（小脑皮质：BP = 2.20 ± 0.72;大脑皮质：BP = 1.05 ± 0.45）。尽管[11 C] AcL 703的脑摄取较低，但区域分布与我们先前对啮齿动物的研究一致。这表明在活体人脑中使用具有[11 C] AcL 703的PET进行NMDA受体的体内评价的可能性。Synapse 61：795-800，2007年。© 2007 Wiley利斯公司
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. Synapse 61:795–800, 2007. © 2007 Wiley‐Liss, Inc.