快速自动化合成^(18)F-FMISO及其质量控制  

Rapidly Automated Synthesis and Quality Control of ^(18)F-Labelled Fluoromisonidazole

作　　者：李琳[1,2] 黄飞杰[1,2] 李敏聪[1,2] 孙华[1,2] 

机构地区：[1]昆明医学院第三附属医院 [2]云南省肿瘤医院PET/CT中心,云南昆明650118

出　　处：《核化学与放射化学》2010年第6期354-361,共8页Journal of Nuclear and Radiochemistry

摘　　要：采用改良的FDG-CPCU,以1-(2’-硝基-1’-咪唑基)-2-O-四氢吡喃基-3-O-甲苯磺酰基丙二醇为原料,经氟化、水解两步法全自动快速合成18F-FMISO。结果表明,合成时间25 min,不校正和校正合成效率分别为(50.3±1.6)%(、61.8±2.3)%,放射性浓度200~220 GBq/L,平均活度2.1×103MBq;TLC法及HPLC法测其放化纯度均大于98%;18F-FMISO的急性毒性及无菌实验未见异常毒性及细菌生长;室温放置6 h及血清温育48 h,18F-FMISO的放化纯度未见明显变化;小鼠尾静脉无菌实验注射18F-FMISO后不同时间处死,测定药物生物分布及药代动力学参数,并由此估算人体内辐射吸收剂量,得到人体肾辐射吸收剂量最高,为24.6μGy(以注入1 MBq18F-FMISO计,下同),全身辐射吸收剂量最低,为8.49μGy,有效剂量为20.5 pSv/Bq。这些资料为临床安全应用18F-FMISO提供了依据。同时,18F-FMISO肺癌模型小鼠生物学分布表明,18F-FMISO适用于心、肺肿瘤的乏氧评价。The rapid automatic synthesis of 1-H-1-（3- fluoro-2-hydro-xylpropyl）-2-nitroimidazole（18F-FMISO） via two-pot procedure was adopted in modifying FDG module and taking 1-（2＇-nitro-1＇-imidazolyl）-2-O-tetra-hydropyranyl-3-O-tosyl-propanediol as labeling precursor in this study.The reaction time is 25 min.The product yield is（50.3±1.6）% with no decay correction,while（61.8±2.3）% with decay correction,radioactivity is 200-220 GBq/L,average concentration is 2.1×103 MBq.The radiochemical purity is above 98% by high-performance liquid chromatography and thin-layer chromatography,respectively.During the experiments of acute-toxicity and sterility tests,abnormal toxicity and the growing of bacteria don＇t be found.There is not obvious variation in radiochemical purity after 6 h standing at room temperature or 48 h incubation in serum.18F-FMISO was injected into mice through tail vein.The mice were sacrificed by cervical dislocation and biodistribution in mice was determined.Radiation dosimetry in humans was calculated on the basis of organ distribution in mice,so as to estimate the radiation safety.The estimation of the kidney in humans receives the highest dose of 24.6 μGy（all the calculation were based on injection 1 MBq of 18F-FMISO,the same below）,the whole body receives the lowest dose of 8.49 μGy.The effective dose is estimated to be 20.5 pSv/Bq.Human radiation dosimetry can be performed by the mice biodistribution data and important data for clinical safe trial of 18F-FMISO are provided.At the same time,its bio-distribution shows that it can be used in clinical practice as a potential radiopharmaceutical for the non-invasive detection of hypexia in heart and lung tumors.

关 键 词：18F-FMISO 快速自动化合成 质量控制 

分 类 号：R817[医药卫生—影像医学与核医学]