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目的 探讨研制99Tcm [N (2 (4 (2 甲氧基苯 ) 1 哌嗪 1 乙基 ) N (2 吡啶 ) 环己烷酰胺 ) ](WAY10 0 6 35 )类似物中枢神经系统 5 羟色胺 1A(5 HT1A)受体显像剂。方法 将化学合成的单齿配体 1 (2 甲氧基苯基 ) 4 (2 巯基乙基 )哌嗪 (MPMEP)和三齿配基N ,N 二 (2 巯基乙基 ) N′,N′ 二乙基乙二胺 (BMPDEEDA)与99Tcm 葡庚糖酸钠 (GH)经三齿配体与单齿配体混合标记方法 (“3+1”)混合配体交换 ,制得99TcmO(MPMEP) (BMPDEEDA)。同时 ,以大鼠脑海马膜组织匀浆为 5 HT1A 受体来源 ,与 5 HT1A受体的特异激动剂3H 2 (二 n 丙胺基 ) 8 羟基 四氢化萘 (8 OH DPAT)进行体外竞争结合实验 ,测定99Tcm 标记物的类似物ReO(MPMEP) (BMPDEEDA)对受体蛋白与特异拮抗 (激动 )剂竞争结合达到一半 (5 0 % )时的浓度 (IC50 值 )。结果 制备的99TcmO(MPMEP) (BMPDEEDA)经高压液相层析 (HPLC)纯化并测定其放化纯度 >95 %。大鼠脑海马摄取在注射后 30、6 0、12 0、180min时 %ID g分别为 0 .0 77、0 .0 6 8、0 .0 84和 0 .0 6 7,放射性摄取最高部位为丘脑 ,注射后 12 0min时 %ID g为 0 .15 4 ,各时相海马与小脑的摄取比值分别为 0 .84 7、0 .880、0 .92 1和 1.2 4 4。ReO(MPMEP) (BMPDEEDA)的IC50为 98.7
OBJECTIVE To investigate the effects of 5-hydroxytryptamine 1A (N-methyl-2-pyrrolidone) on the central nervous system of 99Tcm [N 5 HT1A) receptor imaging agent. Methods The monodentate ligands 1 (2-methoxyphenyl) 4 (2-mercaptoethyl) piperazine (MPMEP) and tridentate ligand N, N bis Diethyl ethylenediamine (BMPDEEDA) and 99Tcm sodium glucoheptonate (GH) were mixed ligand exchange by a tridentate ligand to monodentate ligand mixed labeling method (“3 + 1”) to produce 99TcmO (MPMEP) (BMPDEEDA). At the same time, the rat hippocampal tissue homogenate was used as the source of 5 HT1A receptor, and the in vitro competitive binding assay was carried out in combination with 3H 2 (di-n-propylamino) 8-hydroxytetrahydronaphthalene (8 OH DPAT) , The concentration (IC50 value) at which the analogue of the 99 Tcm marker ReO (MPMEP) (BMPDEEDA) competes for binding of the receptor protein to a specific antagonist (agonist) in half (50%) is determined. As a result, 99TcmO (MPMEP) (BMPDEEDA) was purified by high pressure liquid chromatography (HPLC) and its radiochemical purity was determined to be> 95%. The hippocampal uptake% of rats at 30, 60, 120, 180 min after injection were 0.077, 0.06, 0.084, and 0.067, respectively. The highest radioactive uptake was The thalamus,% ID g was 0.154 at 120 min after injection, and the ratio of hippocampus to cerebellum uptake was 0.84 7,0 .880,0 .92 1 and 1.2 4 4 at each phase. ReO (MPMEP) (BMPDEEDA) has an IC50 of 98.7