Preparation of ^(99m)Tc-PQQE and preliminary biological evaluation for the NMDA receptor

作     者：ZHOU Xingqin KONG Yanyan ZOU Meifen ZHANG Jiankang CAO Guoxian 

作者机构：Key Laboratory of Nuclear MedicineMinistry of HealthJiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear Medicine 

出 版 物：《Nuclear Science and Techniques》 (核技术（英文）)

年 卷 期：2013年第24卷第3期

页      面：31-38页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China(No.30770602) Natural Science Foundation of Jiangsu Province,China(Nos.BK2010157 and BK2011167) 

主　　题：NMDA受体 生物学评价 N-甲基-D-天冬氨酸受体 制备 吡咯喹啉醌 停留时间 生物学特性 放射性物质 

摘      要：The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99m Tc-PQQE was prepared using stannous fluoride (SnF 2 ) as reducing agent. Biological characteristics of 99m Tc-PQQE include lipophilic and the charge properties were compared to 99m Tc-PQQ. The biodistributions of 99m Tc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99m Tc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2β) results indicate that the residence time of 99m Tc-PQQE (203.92) in the body is twice as long as 99m Tc-PQQ (100.45). The uptake of 99m Tc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99m Tc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99m Tc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99m Tc-PQQE has some specific targeting to the NMDA receptor.