^11C-鬼臼毒素的制备及在荷瘤鼠体内的生物学分布

目的 制备^11C-鬼臼毒素（简称鬼臼）和^11C-表鬼臼,研究两者在荷瘤鼠体内的生物学分布.方法 用^11C-三氟甲基磺酰基甲烷（^11C-Triflate-CH3）直接标记去甲基鬼臼和去甲基表鬼臼,产物经HPLC分离,测量11C-鬼臼和^11C-表鬼臼的标记率和放化纯.取雌性荷EMT6乳腺癌小鼠30只,按随机数字表法分成2组,分别经尾静脉注射^11C-鬼臼和11C-表鬼臼3.7 MBq,均于注射后5、10、30 min各处死小鼠5只,取血液、脑、心等组织测质量及放射性计数,计算放射性摄取值（％ID/g）.采用配对t检验进行统计学比较.结果 用^11C-Triflate-CH3直接标记去甲基鬼臼和表鬼臼的标记率均达90％以上,放化纯大于99％.^11C-鬼臼和11C-表鬼臼在荷EMT6乳腺癌小鼠体内分布相似,血液清除慢,腹部放射性高.30 min时肿瘤对^11C-鬼臼和^11C-表鬼臼摄取分别为（3.16±0.27）和（3.63±0.98） ％ID/g,肿瘤/血液比仅为0.62和0.68,肿瘤/肌肉比为1.22和1.52;肿瘤对两者的摄取差异无统计学意义（t=0.47,P＞0.05）.结论 荷瘤鼠肿瘤对^11C-鬼臼摄取量不高,^11C-鬼臼直接用于肿瘤的诊断价值有限.

Synthesis of podo-and epipodo-^11C-podophyllotoxin and their biodistribution in mouse bearing EMT6 tumor

Objective To synthesize podo-and epipodo-podophyllotoxin labeled with ^11C and investigate their biodistribution in mice bearing EMT6 tumor by microPET.Methods ^11 C-podo-or epipodopodophyllotoxin was synthesized by ^11 C-CH3-Triflate mixed with 4＇-methyl-demethmyl-podophyllotoxin （podo-and epipodo-） and purified using HPLC.The radiochemical purity （RCP） was analyzed by HPLC.Thirty mice bearing EMT6 tumor were divided into 2 groups and injected with 3.7 MBq ^11C-podo-or epipodo-podophyllotoxin.The biodistribution of ^11C-podo-or epipodo-podophyllotoxin was evaluated with microPET.The ID%/g was calculated.Paired t test was used to analyze the data.Results The yields of ^11C-podo-and epipodo-podophyllotoxin were both 〉90%.The RCP was 〉99%.The biodistribution of ^11C-podo-and epipodo-podophyllotoxin was similar with slow blood clearance and high uptake in abdomen.The tumor uptake of ^11C-epipodophyllotoxin and ^11C-podophyllotoxin at 30 min was （3.63±0.98） %ID/g and （3.16±0.27） %ID/g,respectively.The uptake ratio of tumor to blood and to muscle was 0.68 vs 0.62 and 1.52 vs 1.22,respectively.There was no significant difference between the tumor uptake of the two agents （t=0.47,P〉0.05）.The result of microPET imaging was consistent with that of mice experiment.Conclusion ^11C-podophyllotoxin has limited clinical value for tumor imaging.