用于成像囊泡乙酰胆碱转运体的两种碳-11标记的强效选择性放射性配体的合成与放射性合成。
Syntheses and radiosyntheses of two carbon-11 labeled potent and selective radioligands for imaging vesicular acetylcholine transporter.
作者信息
Padakanti Prashanth K, Zhang Xiang, Li Junfeng, Parsons Stanley M, Perlmutter Joel S, Tu Zhude
机构信息
Department of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA.
出版信息
Mol Imaging Biol. 2014 Dec;16(6):765-72. doi: 10.1007/s11307-014-0748-x.
PURPOSE
The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. The syntheses and C-11 labeling of two potent enantiopure VAChT inhibitors are reported here.
PROCEDURES
Two VAChT inhibitors, (±)-2 and (±)-6, were successfully synthesized. A chiral HPLC column was used to resolve the enantiomers from each corresponding racemic mixture for in vitro characterization. The radiosyntheses of (-)-[(11)C]2 and (-)-[(11)C]6 from the corresponding desmethyl phenol precursor was accomplished using [(11)C]methyl iodide or [(11)C]methyl triflate, respectively.
RESULTS
The synthesis of (-)-[(11)C]2 was accomplished with 40-50 % radiochemical yield (decay-corrected), SA > 480 GBq/μmol (EOB), and radiochemical purity >99 %. Synthesis of (-)-[(11)C]6 was accomplished with 5-10 % yield, SA > 140 GBq/μmol (EOB), and radiochemical purity >97 %. The radiosynthesis and dose formulation of each tracer was completed in 55-60 min.
CONCLUSIONS
Two potent enantiopure VAChT ligands were synthesized and (11)C-labeled with good radiochemical yield and specific activity.
目的
囊泡乙酰胆碱转运体（VAChT）是用于成像突触前胆碱能神经元的一种特异性生物标志物。本文报道了两种强效对映体纯VAChT抑制剂的合成及碳-11标记。
程序
成功合成了两种VAChT抑制剂（±）-2和（±）-6。使用手性高效液相色谱柱从每种相应的外消旋混合物中拆分对映体以进行体外表征。分别使用碘甲烷或三氟甲磺酸甲酯由相应的去甲基苯酚前体完成（-）-[（11）C]2和（-）-[（11）C]6的放射性合成。
结果
（-）-[（11）C]2的合成放射性化学产率为40 - 50%（衰变校正），比活度>480 GBq/μmol（放化结束时），放射性化学纯度>99%。（-）-[（11）C]6的合成产率为5 - 10%，比活度>140 GBq/μmol（放化结束时），放射性化学纯度>97%。每种示踪剂的放射性合成和剂型制备在55 - 60分钟内完成。
结论
合成了两种强效对映体纯VAChT配体并进行了碳-11标记，放射性化学产率和比活度良好。
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