摘要
目的探索国产^(177)Lu-前列腺特异膜抗原(PSMA)-617的最佳标记条件,研究其生物分布、稳定性及安全性。方法手动合成国产^(177)Lu-PSMA-617,确定最佳标记条件,检测其放化纯、体内外稳定性、脂水分配系数及血浆蛋白结合率;评价前列腺癌细胞22RV1对其的摄取率;设置进口^(177)Lu-PSMA-617对照组,研究2种标记物在正常小鼠体内的生物分布及其SPECT/CT显像特点;通过测定小鼠血常规等,评估药物安全性。结果国产^(177)Lu-PSMA-617在pH值4.5、100℃恒温条件下反应30 min即可得到最佳标记结果,产物放化纯≥99%,72 h内放化纯仍>95%,体内外稳定性好。在体外的血浆蛋白结合率为(35.3±5.3)%,脂水分配系数为-2.27±0.06,22RV1细胞对国产^(177)Lu-PSMA-617的特异性摄取率在1 h达最高[(7.58±0.84)%],略低于进口^(177)Lu-PSMA-617,但差异无统计学意义[(7.86±0.96)%;t=-0.439,P>0.05]。正常小鼠体内分布及显像表明,国产和进口^(177)Lu-PSMA-617在血液清除速率相当,主要经肾排泄。两者毒性实验均未见明显不良反应,血常规、肝肾功能未见明显异常。结论国产^(177)Lu-PSMA-617质控合格,产物具有良好的生物学性能及安全性,在前列腺肿瘤的诊断中有潜在的应用价值。
Objective To synthesize ^(177)Lu-prostate-specific membrane antigen(PSMA)-617 with domestic ^(177)Lu(made in China),and explore its optimal labeling condition,biodistribution,stability,and safety.Methods ^(177)Lu-PSMA-617 was prepared with domestic ^(177)Lu by a manual method.The optimal labeling condition,radiochemical purity,stability(in vivo and in vitro),lipid-water partition coefficient,and plasma protein binding rate were determined.The uptake rate of ^(177)Lu-PSMA-617 was evaluated by using 22RV1 cells.Biodistribution and SPECT/CT imaging were performed on normal mice with imported ^(177)Lu-PSMA-617 as control group.The blood routine test was performed to evaluate the safety.Results The best labeling result of domestic ^(177)Lu-PSMA-617 can be obtained under the following conditions:pH=4.5,100℃for 30 min.And the radiochemical purity was≥99%.The product was stable in vivo and in vitro,with the radiochemical purity>95%in 72 h.The plasma protein binding rate was(35.3±5.3)%,the lipid-water partition coefficient was-2.27±0.06,and the specific uptake rate of domestic ^(177)Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h((7.58±0.84)%),which was slightly lower than the imported ^(177)Lu-PSMA-617((7.86±0.96)%),but there was no significant difference between them(t=-0.439,P>0.05).The distribution and SPECT/CT imaging of normal mice showed that domestic and imported ^(177)Lu-PSMA-617 in blood were cleared quite fast,and both of them were excreted mainly through the kidneys.No obvious adverse reactions were found in the toxicity test of domestic and imported ^(177)Lu-PSMA-617.There was no obvious abnormality in blood routine and liver and kidney metabolism.Conclusion The domestic ^(177)Lu-PSMA-617 has many advantages,such as qualified quality control,good biological properties and safety,which support its potential application value in diagnosis of prostatic neoplasms.
作者
张心怡
傅文会
徐婷婷
曾成润
夏雨霄
刘会攀
陈琳
漆赤
杨宇川
魏洪源
陈跃
Zhang Xinyi;Fu Wenhui;Xu Tingting;Zeng Chengrun;Xia Yuxiao;Liu Huipan;Chen Lin;Qi Chi;Yang Yuchuan;Wei Hongyuan;Chen Yue(Department of Nuclear Medicine,the Affiliated Hospital of Southwest Medical University,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province,Academician(Expert)Workstation of Sichuan Province,Luzhou 646000,China;Institute of Nuclear Physics and Chemistry,China Academy of Engineering Physics,Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province,Mianyang 621900,China)
出处
《中华核医学与分子影像杂志》
CAS
CSCD
北大核心
2021年第5期296-302,共7页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
核医学与分子影像四川省重点实验室建设基金(2018JPT0023)
核医学创新转化平台(2019JDPT0004)。
关键词
前列腺肿瘤
前列腺特异膜抗原
二肽类
同位素标记
镥
放射性核素显像
小鼠
Prostatic neoplasms
Prostate-specific membrane antigen
Dipeptides
Isotope labeling
Lutetium
Radionuclide imaging
Mice
作者简介
通信作者:陈跃,Email:chenyue5523@126.com。
