摘要
目的制备国产^(64)Cu-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(DOTATATE),验证其在神经内分泌肿瘤(NETs)中的分布及初步临床应用价值。方法采用国产^(64)Cu标记获得^(64)Cu-DOTATATE,进行脂水分配系数、体外稳定性和药代动力学研究。在荷人肺支气管肿瘤细胞NCI-H727[生长抑素受体(SSTR)2阳性表达]裸鼠上行生物分布实验及microPET显像,并在2023年5月至2024年4月间解放军总医院10例NETs患者[男5例、女5例,年龄(58.5±13.0)岁]中进行初步临床应用。采用两独立样本t检验分析数据。结果成功制备^(64)Cu-DOTATATE,放化纯大于98%,脂水分配系数logP为-2.609±0.051,稳定性好。BALB/c小鼠药代动力学实验提示药物血液清除较快(清除半衰期为22.78min),荷瘤鼠生物分布结果显示^(64)Cu-DOTATATE主要通过肝、肾代谢,注射后1 h肿瘤就有明显摄取[(2.519±0.273)每克组织百分注射剂量率(%ID/g)],注射后24 h仍保持较高的摄取[(4.331±0.549)%ID/g]。MicroPET显像示,注射后24h,肿瘤摄取略有增加并保持较好的滞留,较阻断组差异有统计学意义[(2.197±0.250)和(0.985±0.064)%ID/g;t=6.40,P=0.008];肿瘤/肝比值在1、2、6、24h分别为0.075±0.007、0.083±0.011、0.118±0.005、0.263±0.031。初步临床应用表明,^(64)Cu-DOTATATE在患者体内靶向性好,肝放射性分布适中(SUV_(max)=10.62±3.46),可得到较好的图像质量。结论国产^(64)Cu-DOTATATE PET/CT显像对NETs是很有前景的影像评估手段,有进一步临床研究的价值。
Objective To prepare domestic ^(64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide(DOTATATE),and to verify its distribution and preliminary diagnostic value in neuroendocrine tumors(NETs).Methods DOTATATE was labeled with the domestic ^(64)Cu to obtain ^(64)Cu-DOTATATE.The lipophilicity,in vitro stability,and pharmacokinetics were studied.Biodistribution experiments and microPET imaging were performed on NCI-H727(somatostatin receptor(SSTR)2 positive expression)tumor-bearing nude mice.The preliminary clinical applications were conducted on 10 NETs patients(5 males,5 females;age(58.5±13.0)years)from Chinese PLA General Hospital between May 2023 and April 2024.Data were analyzed by using independent-sample t test.Results ^(64)Cu-DOTATATE was successfully prepared with the radiochemical purity greater than 98%,log P of-2.609±0.051 and good stability.Pharmacokinetic experiments in BALB/c mice suggested rapid blood clearance of the drug(elimination half-time of 22.78min).Biodistribution results in tumor-bearing mice showed that ^(64)Cu-DOTATATE was mainly metabolized through the liver and kidneys,with significant tumor uptake at 1h((2.519±0.273)percentage activity of injection dose per gram of tissue(%ID/g))and sustained high uptake at 24h((4.331±0.549)%ID/g).MicroPET imaging of tumor-bearing mice showed a slight increase in uptake and good retention at 24h,with a significant statistical difference compared to the blocked group((2.197±0.250)vs(0.985±0.064)%ID/g;t=6.40,P=0.008).The tumor/liver ratios were 0.075±0.007,0.083±0.011,0.118±0.005,0.263±0.031 at 1,2,6 and 24h,respectively.Preliminary clinical application indicated that ^(64)Cu-DOTATATE exhibited good targeting in patients,and the liver radioactivity distribution was moderate(SUV_(max)=10.62±3.46),providing good image quality.Conclusion Domestic ^(64)Cu-DOTATATE PET/CT imaging is a promising imaging evaluation method in NETs with the value for further clinical research.
作者
刘欢欢
张晓军
麻广宇
潘越
张靖峰
文辉
徐晓丹
王瑞民
张锦明
Liu Huanhuan;Zhang Xiaojun;Ma Guangyu;Pan Yue;Zhang Jingfeng;Wen Hui;Xu Xiaodan;Wang Ruimin;Zhang Jinming(Department of Nuclear Medicine,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)
出处
《中华核医学与分子影像杂志》
北大核心
2025年第6期358-363,共6页
Chinese Journal of Nuclear Medicine and Molecular Imaging
关键词
神经内分泌瘤
肽类
同位素标记
铜
小鼠
裸
Neuroendocrine tumors
Peptides
Isotope labeling
Copper
Mice,nude
作者简介
通信作者:张锦明,Email:zhangjm301@163.com。
