抗癌中药活性成分毛兰素衍生物^(18)F-FEE的^(18)F标记及其体内性质MicroPET/CT评价  

^(18)F radiolabeling and MicroPET/CT evaluation of in vivo properties of^(18)F-FEE as the derivative of erianin,an active component of anticancer traditional Chinese medicine

作　　者：王撵 张丰盛 张勇平 宋少莉[2,3,4] 杨红 王明伟 WANG Nian;ZHANG Fengsheng;ZHANG Yongping;SONG Shaoli;YANG Hong;WANG Mingwei(College of Chemistry and Materials Sciences,Shanghai Normal University,Shanghai 200234,China;Department of Nuclear Medicine,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Center for Biomedical Imaging,Fudan University,Shanghai 200032,China;Engineering Research Center of Molecular Imaging Probes,Shanghai 200032,China)

机构地区：[1]上海师范大学化学与材料科学学院,上海200234 [2]复旦大学附属肿瘤医院核医学科,复旦大学上海医学院肿瘤学系,上海200032 [3]复旦大学生物医学影像研究中心,上海200032 [4]上海分子影像探针工程技术研究中心,上海200032

出　　处：《肿瘤影像学》2022年第4期372-379,共8页Oncoradiology

基　　金：国家自然科学基金(21771041)。

摘　　要：目的:开展抗癌中药活性成分毛兰素衍生物氟乙氧基毛兰素(fluoroethoxylerianin,FEE)的^(18)F标记及^(18)F-FEE的Micro正电子发射体层成像(positron emission tomography,PET)/计算机体层成像(computed tomography,CT),初步探索^(18)F等正电子核素标记与PET/CT在中药活性成分来源的新药评价中的应用。方法:开展^(18)F-FEE的制备条件优化实验,包括影响^(18)F标记和水解反应的多种反应条件,利用放射性薄层色谱法(radio-TLC)检测标记率和水解效率,放射性高效液相色谱法(radio-HPLC)测量^(18)F-FEE的放射化学纯度,并进行正常BALB/c小鼠与HepG2细胞的BALB/c裸小鼠移植瘤模型的体内生物分布和MicroPET/CT评价。结果:优化的^(18)F标记反应条件是时间10 min、温度100℃、前体浓度5 mg/mL、溶剂为乙腈,优化的水解反应条件是时间10 min、温度100℃、HCl溶液浓度6 mol/L。根据优化条件,成功合成了^(18)F-FEE,其放射化学纯度大于95%。正常小鼠生物分布和MicroPET/CT显示,^(18)F-FEE主要分布于肝、肠、肾和膀胱等代谢组织,心、肺等组织的分布较低。HepG2肝癌细胞移植瘤模型MicroPET/CT发现,^(18)F-FEE长时间弥散分布于肿瘤组织,肿瘤%ID/g高,注射60 min后肿瘤-肌肉比值(T/M)高达10以上。结论:本研究优化了抗癌中药活性成分毛兰素衍生物^(18)F-FEE的优化制备条件,^(18)F-FEE的合成条件可靠、放射化学纯度高,在体内主要分布于肝、肠、肾等代谢组织,而且其在HepG2肿瘤内分布明显,为FEE抗肿瘤作用提供了直观的实验手段,为抗癌天然活性中药成分及其衍生物提供了新的评价技术。Objective:To investigate^(18)F radiolabeling fluoroethoxylerianin(FEE)and Micro positron emission tomography(PET)/computed tomography(CT)of^(18)F-FEE,a derivative of an active ingredient of anticancer traditional Chinese medicine(TCM)erianin,and to preliminarily explore the applications of positron nuclide labeling such as^(18)F and PET/CT into the evaluation of new drugs derived of the active components of TCM.Methods:The optimized preparation conditions of^(18)F-FEE were carried out,including the multiple reaction parameters affecting^(18)F radiolabeling and hydrolysis.The radiolabeling rate and hydrolysis efficiency were detected by radio-TLC,and the radiochemical purity of^(18)F-FEE was measured by radio-HPLC.The biodistribution and MicroPET/CT of^(18)F-FEE in normal BALB/c mice and HepG2 xenograft model in BALB/c nude mice were performed.Results:The optimized conditions of^(18)F radiolabeling reaction were time 10 min,temperature 100℃,precursor concentration of 5 mg/mL and solvent as MeCN.The optimized hydrolysis reaction conditions were time 10 min,temperature 100℃and hydrochloric acid concentration of 6 mol/L.According to the optimized conditions,^(18)F-FEE was successfully synthesized with the radiochemical purity of more than 95%.The biodistribution and MicroPET/CT in normal rats showed that^(18)F-FEE was mainly distributed in metabolic tissues such as liver,intestine,kidney and bladder,while the distribution of heart,lung and other tissues was low.MicroPET/CT in HepG2 liver cancer models showed that^(18)F-FEE was diffusely distributed in tumor tissues for a long time with high tumor%ID/g,and the T/M was more than 10 at 60 min post injection.Conclusion:This study optimized and established the^(18)F radiolabeling conditions of^(18)F-FEE as the derivative of erianin,an active ingredient of anti-cancer TCM.The synthesis conditions of^(18)F-FEE were reliable with high radiochemical purity.^(18)F-FEE was mainly distributed in vivo in liver,intestine,kidney and other metabolic tissues,and significantly dis

关 键 词：^(18)F标记 正电子发射体层成像/计算机体层成像 中药活性成分 毛兰素 肿瘤 

分 类 号：R445.6[医药卫生—影像医学与核医学]