^(68)Ga-DOTATATE注射液放化纯与体内显像效果关系的研究  

Study on the relation of the radiochemical purity and in vivo imaging effect of ^(68)Ga-DOTATATE injection

作　　者：贾娟娟[1] 党永红 孙得洋 孙葭北 程茗 霍力 施亚琴[1] Jia Juanjuan;Dang Yonghong;Sun Deyang;Sun Jiabei;Cheng Ming;Huo Li;Shi Yaqin(Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Medical Products Administration Division of Antitumor&Radioactive Drug,National Institutes for Food and Drug Control,Beijing 102629,China;Department of Nuclear Medicine,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine,Beijing 100730,China)

机构地区：[1]国家药品监督管理局化学药品质量研究与评价重点实验室,中国食品药品检定研究院抗肿瘤和放射性药品室,北京102629 [2]中国医学科学院、北京协和医学院北京协和医院核医学科、核医学分子靶向诊疗北京市重点实验室,北京100730

出　　处：《中华核医学与分子影像杂志》2022年第6期335-339,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家科技重大专项(2017zx09101001-007)。

摘　　要：目的:探讨^(68)Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(TATE)注射液放化纯与体内显像效果的关系。方法:采用高效液相色谱(HPLC)和薄层色谱(TLC)法测定^(68)Ga-DOTATATE、^(68)Ga^(3+)、^(68)Ga胶体及^(68)Ga-DOTA-D-苯丙氨酸1-酪氨酸3-苏氨酸8-去苏氨酸-奥曲肽(heptapeptide),考察标记前体DOTATATE的纯度对标记产物放化纯的影响。建立大鼠胰腺外分泌腺肿瘤细胞AR42J荷瘤裸鼠模型,行microPET显像,考察不同放化纯^(68)Ga-DOTATATE注射液的摄取情况,计算肿瘤组织的靶/非靶(T/NT)比值。采用单因素方差分析和Pearson相关分析数据。结果:^(68)Ga^(3+)和^(68)Ga胶体的含量与标记前体DOTATATE的纯度无明显相关性(r值:0.385、0.497,P值:0.306、0.137),^(68)Ga-DOTA-heptapeptide的含量与标记前体中DOTA-heptapeptide的纯度呈正相关(r=0.957,P<0.001)。纯度分别为90.9%、91.6%、99.2%的DOTATATE,其标记产物^(68)Ga-DOTATATE注射液的放化纯分别为(87.0±2.3)%、(86.8±0.8)%、(94.0±3.1)%。MicroPET显像示,将放化纯为95.7%、85.8%、84.5%和79.9%的^(68)Ga-DOTATATE注射液分别注入荷瘤裸鼠体内,肿瘤组织的摄取与放化纯呈正相关(r=0.828,P<0.001),其T/NT比值分别为21.25±8.84、8.50±1.51、11.38±1.65和6.01±0.99(F=11.48,P=0.001)。结论:^(68)Ga-DOTATATE注射液的放化纯受标记前体纯度及制备工艺的影响,其放化纯与体内显像效果有一定关系。Objective To explore the relation of the radiochemical purity and in vivo imaging effect of ^(68)Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)-D-phe1-Tyr3-Thr8-octreotide(TATE)injection.Methods High performance liquid chromatography(HPLC)and thin-layer chromatography(TLC)methods were established to determine ^(68)Ga-DOTATATE,^(68)Ga^(3+),^(68)Ga in colloidal form and ^(68)Ga-DOTA-D-Phe1-Tyr3-Thr8-dethreonine-octreotide(heptapeptide)and to study the influence of precursor purity on radiochemical purity of labelled products.The uptake of ^(68)Ga-DOTATATE injection with different radiochemical purities was investigated in nude mice bearing AR42J cells by microPET imaging and the tumor target/non-target(T/NT)value was calculated.One-way analysis of variance and Pearson correlation analysis were used to analyze the data.Results The contents of ^(68)Ga^(3+)and ^(68)Ga in colloidal form were not related with precursor purity(r values:0.385,0.497,P values:0.306,0.137),while the content of ^(68)Ga-DOTA-heptapeptide was positively related with the purity of DOTA-heptapeptide(r=0.957,P<0.001).The radiochemical purities of ^(68)Ga-DOTATATE injection were(87.0±2.3)%,(86.8±0.8)%and(94.0±3.1)% when the DOTATATE purities were 90.9%,91.6% and 99.2%,respectively.The results of microPET imaging showed that the tumor uptake was positively related with the radiochemical purity of ^(68)Ga-DOTATATE injection(r=0.828,P<0.001),and the T/NT values of ^(68)Ga-DOTATATE injection with radiochemical purities of 95.7%,85.8%,84.5% and 79.9% were 21.25±8.84,8.50±1.51,11.38±1.65 and 6.01±0.99,respectively(F=11.48,P=0.001).Conclusion The radiochemical purity of ^(68)Ga-DOTATATE injection is impacted by the purity of labelled precursor and manufacturing processes and is related with the imaging effect in vivo.

关 键 词：有机金属化合物 镓放射性同位素 质量控制 色谱法 高压液相 色谱法 薄层 正电子发射断层显像术 胰腺肿瘤 小鼠 裸 

分 类 号：R817[医药卫生—影像医学与核医学]