摘要
目的利用188Re标记CT/MR双模态纳米颗粒BaGdF5-聚乙二醇(PEG),观察其对肝癌细胞增殖的影响并将其用于SPECT显像。方法采用水热法合成纳米颗粒BaGdF5-PEG,以二乙撑三胺五乙酸(DTPA)作为双功能螯合剂进行188Re标记。四甲基偶氮唑蓝(MTT)法检测不同浓度BaGdF5-PEG、188ReO4-、188Re-DTPA-BaGdF5作用24 h后肝癌细胞SMCC 7721的增殖率。经兔耳缘静脉注射188ReO4-后30、60 min行SPECT全身及CT断层显像,注射188Re-DTPA-BaGdF5后分别行10 min内SPECT动态显像及30、60、120 min后SPECT/CT显像。建立兔肝VX2瘤模型,将微导管经兔股动脉插管至肝动脉,将188Re-DTPA-BaGdF5与碘油的混合液注入肝肿瘤,30 min后行SPECT/CT显像。组间数据比较采用两样本t检验。结果BaGdF5-PEG粒径约10 nm,呈近方形。188Re-DTPA-BaGdF5最大标记率为94.1%,具有良好的体内外稳定性。BaGdF5-PEG对肝癌细胞的增殖无明显影响;188ReO4-和188Re-DTPA-BaGdF5均能抑制肝癌细胞的增殖,且放射性浓度为74.0、370.0×104 Bq/ml时,后者对细胞的增殖抑制作用强于前者(t=4.21、4.09,均P〈0.01)。在体内,188ReO4-主要被兔颌面腺体摄取,并很快经肾脏代谢进入膀胱;188Re-DTPA-BaGdF5经静脉入血后迅速被肝、脾摄取,经肝动脉介入给药后其在肝肿瘤部位高浓度聚集。结论188Re-DTPA-BaGdF5在体外对肝癌细胞增殖具有抑制作用,经肝动脉介入给药后其在肝肿瘤部位聚集;该药不仅可用于肿瘤SPECT显像,还有潜在的治疗作用。
ObjectiveTo investigate the inhibitory effect of 188Re-labeled BaGdF5-poly(ethylene glycol)(PEG) nanoparticles (NPs) on hepatoma cells, and explore the application of the radiolabeled NPs for SPECT imaging.MethodsBaGdF5-PEG NPs were synthesized by hydrothermal method, and were further radiolabeled with 188Re using diethylene triamine pentaacetic acid (DTPA) as a coupling agent. The human hepatoma cells SMCC 7721 were treated with different concentrations of BaGdF5-PEG NPs, 188ReO4- or 188Re-DTPA-BaGdF5 NPs (14.8, 74.0, 370.0×104 Bq/ml) for 24 h, and then the cell proliferation rates were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. 188ReO4- and 188Re-DTPA-BaGdF5 NPs were administrated into normal rabbits via the ear vein, respectively. For the former, static SPECT/CT imaging were performed at 30, 60 min post-injection, and for the latter, dynamic SPECT images were captured within 10 min, and static SPECT/CT images at 30, 60, 120 min post-injection. The rabbit VX2 tumor model was established, and a microcatheter was inserted into hepatic artery via the rabbit femoral artery, and then the mixture of 188Re-DTPA-BaGdF5 NPs and lipiodol was injected into the tumor region. SPECT/CT imaging for VX2 tumor was performed at 30 min later. Data were analyzed by two-sample t test.ResultsThe BaGdF5-PEG NPs were nearly square and the particle size was about 10 nm. The labeling yield of 188Re-DTPA-BaGdF5 was 94.1% at the optimum conditions. Moreover, it showed high stability in vitro and in vivo. In vitro, BaGdF5-PEG NPs did not exhibit obvious cytotoxicity even at a high concentration. Both 188ReO4- and 188Re-DTPA-BaGdF5 could inhibit the proliferation of SMCC 7721 cells, but 188Re-DTPA-BaGdF5 showed a significantly stronger inhibitory effect at the doses of 74.0 and 370.0×104 Bq/ml (t values: 4.21, 4.09, both P〈0.01). In vivo,188ReO4- was absorbed by maxillary glands and was quickly eliminated from blood via the kidneys. The 188Re-DTPA-BaGdF5 NPs mainly accumulated in the liver and spleen. In addition, retention and accumulation of 188Re-DTPA-BaGdF5 NPs in the liver tumor could be achieved by using transarterial intervention technique for drug delivery.Conclusion188Re-DTPA-BaGdF5 NPs have certain killing effects on hepatoma cells in vitro, and with the help of transarterial intervention technique, the NPs can be aggregated within liver tumor, where they not only can be used for SPECT imaging, but also have potential therapeutic effects.
作者
王涛
彭烨
李潇
贾国荣
王秋虎
程超
孙高峰
左长京
Wang Tao;Peng Ye;Li Xiao;Jia Guorong;Wang Qiuhu;Cheng Chao;Sun Gaofeng;Zuo Changjing(Department of Nuclear Medicine,Changhai Hospital,Navy Medical University,Shanghai 200433,China)
出处
《中华核医学与分子影像杂志》
CAS
北大核心
2018年第11期721-725,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
国家自然科学基金(81471714)
长海医院青年启动基金(CH201714)