11C-PK11195的自动化合成及其生物学分布

目的 研究N-[11C]甲基-N-(1-甲基丙基)-1-(2.氯苯基)异喹啉-3-氨甲酰(11C-PK11195)在国内现有合成模块上的自动化合成程序及其在小鼠体内的生物学分布.方法 以1-(2-氯苯基)-N-(1-甲基丙基)-异喹啉-3-氨甲酰去甲基前体与国产模块生产的11C-CH3I在TracerLabFXF-N自动化合成模块中进行甲基化反应,制备11C-PK11195,测定11C-PK11195的纯度和稳定性,观察11C-PK11195在小鼠体内的生物学分布[以每克组织百分注射剂量率(%ID/g)表示]和异常毒性,并进行健康家猫PET显像.结果 从11C-CO2生产到11C-PK11195合成结束总的合成时间约35 min,甲基化合成11C-PK11195的放化产率为(47±3.6)%,其放化纯和化学纯度均>98%,比活度为30～65 GBq/μmol,"C-PK11195注射液室温放置1 h内放化纯>95%.生物学分布实验表明,11C-PK11195在小鼠体内的清除较快,1 min时为(21.44±3.08)%ID/g,60 ndn下降到(1.35±0.54)%ID/g,肾为其主要的排泄器官.注射后1～5 min内,鼠脑放射性水平较高,随后脑内放射性快速下降;心、肺和肾组织中的放射性较高.猫PET显像示肝和肠道摄取最高,其次为肾、肺、大脑、心肌、胃、脾和膀胱,脑组织中放射性分布均匀.结论 该方法可制备出满足临床应用的11C-PK11195,其合成程序也适合于在国内其他模块中应用.11C-PK11195可望用于国内临床PET显像研究.在注射显像剂后30～40 min进行PET显像,可获得较佳PET图像.

Automated synthesis and biodistribution of 11C-PK11195

Objective The aims of this study was to synthesize 1-(2-chlorophenyl)-N-[11C] meth-yl-N-(1-methylpropyl)-3-isoquinoline carboxamide (11C-PK11195) on the commercial synthesizer, and to investigate its biodistribution in mice. Methods 11C-CH3I was synthesized via liquid phase distillation ap-proach on the 11C-iodomethane synthesizer.11C-PK11195 was prepared by 11C-methylation of a correspond-ing demethyl precursor (N-demethyl-PK11195) with 111C-CH3I on TracerLab FXF-N synthesizer. The radio-chemical purity, chemical purity and stability of 11C-PK11195 were measured by high performance liquid chromatography (HPLC). Toxicity and biodistribution (percentage activity of injection dose per gram of tis-sue, % ID/g) in mice were also observed. A normal eat PET imaging of 11C-PK11195 was performed at 20 min after intravenous injection. Results The uncorrected radiochemical yield of 11C-PK11195 was (47±3.6)%. After purification, radiochemical purity, chemical purity, and specific activity of 11C-PK11195 was >98%,>98%, and 30～65 GBq/μmol respectively. The preparation of 11C-PK11195 was about 35 min from 11C-carbon dioxide produced by cyclotron. Product was radiochemically stable at room temperature within 60 min. After tail vein injection of 11>C-PK11195, the activity of 11C-PK11195 was rapidly cleaned from mice blood, the radioactivity level in blood decreased from (21.44±3.08) % ID/g at 1 min to (1.35±0.54) %ID/g at 60 min after injection. The brain radioactivity was high between 1 to 5 rain after injection and was decreased quickly afterwards. Of the peripheral organs, heart had the highest uptake, followed by lungs and kidneys. At 20 min after injection, most of the 11C-PK11195 was accumulated in liver, intestinal tract, kidney, lung, brain, heart, stomach, spleen and brain cortex. Conclusion We demonstrated a us-er-friendly synthetic procedure with an automated synthesizer, which could provide a high quality and an op-timal amount 11C-PK11195.