正电子核素^(68)Ga标记PSMA靶向分子探针在神经胶质瘤模型中的应用  

Application of ^(68)Ga-PSMA-617 Molecular Probe for Micro-PET Imaging of Gliomas Model

作　　者：韩雪迪 刘菲[1] 郭晓轶 徐晓霞 解清华 刘特立 朱华[1] 杨志[1] HAN Xuedi;LIU Fei;GUO Xiaoyi;XU Xiaoxia;XIE Qinghua;LIU Teli;ZHU Hua;YANG Zhi(Key Laboratory of Carcinogenesis and Translational Research （Ministry of Education）, Department of Nuclear Medicine, Peking University Cancer Hospital ＆ Institute, Beijing 100142, China;College of Chemistry, Sichuan University, Chengdu 610064, China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]四川大学化学学院,成都610064

出　　处：《肿瘤防治研究》2018年第7期447-452,共6页Cancer Research on Prevention and Treatment

基　　金：方正创新药物研究基金(20150391);北京市卫生局基金215学科骨干(2015-3-072)

摘　　要：目的探讨^(68)Ga-PSMA-617在神经胶质瘤U87MG荷瘤鼠的显像情况。方法将靶向前列腺特异性膜抗原(prostate specific membrane antigen,PSMA)的新型探针DKFZ-PSMA-617进行^(68)Ga核素标记,利用Radio-TLC对^(68)Ga-PSMA-617的放射化学纯度进行快速质控,然后进行细胞水平实验,尾静脉注射5和40 min后对U87MG荷瘤鼠进行micro-PET显像,同时对PSMA阻滞剂ZJ-43(25 mg/kg)共注射组进行注射后40 min的图像采集。结果 Radio-TLC对^(68)Ga-PSMA-617的标记率及放化纯测定可在10min内完成,放化纯高达(99.0±1.9)%,细胞水平实验显示^(68)Ga-PSMA-617分子探针的特异性,同时也显示U87MG细胞表面仅有较少量PSMA表达,而U87MG荷瘤鼠的micro-PET显像可见随时间延长肿瘤对PSMA靶向分子探针的放射性摄取的逐渐增高,靶与非靶比值从1.85±0.02(5 min)增长至3.62±0.175(40 min),且肿瘤对该探针的摄取可被PSMA阻滞剂ZJ-43所抑制。结论 ^(68)Ga-PSMA-617不仅可应用于前列腺癌的诊断,也有望应用于新生血管丰富的神经胶质瘤的诊断。Objective To investigate the application of 68Ga-PSMA-617 molecular probe for micro-PET imaging of gliomas tumor model. Methods DKFZ-PSMA-617, an effective prostate specific membrane antigen （PSMA） targeted probes, was chosen to be the precursor to be radiolabelled with 68Ga. The radiochemical yield of 68Ga-PSMA-617 was analyzed by Radio-TLC. Cell uptake experiments were performed on PSMA （＋） LNCaP, PSMA （-） PC-3 and U87MG cells. Nude mice bearing U87MG were injected with 68Ga-PSMA-617（7.4 MBq） via the tail vein. Micro-PET imaging was performed 5 and 40 min after the injection. Blocking studies were also performed in U87MG tumor-bearing mice after 40 min of co-injection of 68Ga-PSMA-617 with the PSMA inhibitor （S）-2-（3-（（S）-1-carboxy-3-methylbutyl）ureido） pentanedioic acid （ZJ-43） （25 mg/kg）. Results The radiotracer had a good radio-chemical yield of （99.0±1.9）% quickly tested by Radio-TLC. In cell uptake experiments, the specificity of 68Ga-PSMA-617 was confirmed in PSMA （＋） LNCaP cells and PSMA （-） PC-3 cells; meanwhile, it proved the low expression level of PSMA in gliomas U87MG cell line. From micro-PET imaging, U87MG xenografts tumors were visualized and it showed good tumor-to-background value from 1.85±0.02 （5 min） to 3.62±0.175 （40 min） which could be blocked by ZJ-43. Conclusion 68Ga-PSMA-617 has the potential to be used not only in prostate cancer but also in gliomas tumor model.

关 键 词：前列腺特异性膜抗原 新生血管 正电子发射断层扫描 神经胶质瘤 镓-68 

分 类 号：R739.4[医药卫生—肿瘤]