^11C-PK11195的自动化合成及其生物学分布

Automated synthesis and biodistribution of ^11C-PK11195

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TracerLab FXF-X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“C—PK11195合成结束总的合成时间约35min，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30～65GBq／μmol，^11C—PK11195注射液室温放置1h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，1min时为（21．44±3．08）％ID／g，60min下降到（1．35±0．54）％ID／g，肾为其主要的排泄器官。注射后1-5min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30～40min进行PET显像，可获得较佳PET图像。

Objective The aims of this study was to synthesize 1- （2-chlorophenyl） -N- [ ^11C ] methyl-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 approach on the ^11C-iodomethane synthesizer. ^11C-PK11195 was prepared by ^11C-methylation of a corresponding demethyl precursor （ N-demethyl-PK11195 ） with ^11C-CH3I on TracerLab FXF-N synthesizer. The radiochemical 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 tissue, % ID/g） in mice were also observed. A normal cat PET imaging of ^11C-PK11195 was performed at 20 min after intravenous injection. Results The uncorrected radiochemical yield of 11C-PK^11195 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 HC-PK11195 was about 35 rain from ^11 C-carbon dioxide produced by cyclotron. Product was radiochemically stable at room temperature within 60 min. After tail vein injection of ^11C-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 rain to （ 1.35 ± 0. 54） %ID/g at 60 min after injection. The brain radioactivity was high between 1 to 5 min after injection and was decreased quickly afterwards. Of the peripheral organs, heart had the highest uptake, followed by lungs and kidneys. At 20 rain 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 user-friendly synthetic procedure with an automated synthesizer, which could provide a high quality and an optimal amount^11C-PK11195.