刘艳迪, 刘江, 刘印忠, 常克力, 何景华. 153Sm半乳糖多聚赖氨酸肝细胞靶向全肝照射治疗肝癌的实验研究[J]. 中国肿瘤临床, 2012, 39(14): 949-951, 961. DOI: 10.3969/j.issn.1000-8179.2012.14.003
引用本文: 刘艳迪, 刘江, 刘印忠, 常克力, 何景华. 153Sm半乳糖多聚赖氨酸肝细胞靶向全肝照射治疗肝癌的实验研究[J]. 中国肿瘤临床, 2012, 39(14): 949-951, 961. DOI: 10.3969/j.issn.1000-8179.2012.14.003
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Yan-di LIU, Jiang LIU, Yin-zhong LIU, Ke-li CHANG, Jing-hua HE. Lac-PLL-DTPA-153Sm for the Treatment of Liver Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(14): 949-951, 961. DOI: 10.3969/j.issn.1000-8179.2012.14.003
Citation: Yan-di LIU, Jiang LIU, Yin-zhong LIU, Ke-li CHANG, Jing-hua HE. Lac-PLL-DTPA-153Sm for the Treatment of Liver Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(14): 949-951, 961. DOI: 10.3969/j.issn.1000-8179.2012.14.003
shu

153Sm半乳糖多聚赖氨酸肝细胞靶向全肝照射治疗肝癌的实验研究

Lac-PLL-DTPA-153Sm for the Treatment of Liver Cancer

    摘要
  • 摘要:
      目的  探讨利用乳糖化赖氨酸作为肝细胞靶向载体, 将放射性核素153Sm特异性地浓集至肝脏, 用全肝内照射的方法治疗肝癌的可行性, 为原发性肝癌的治疗提供依据。
      方法  聚赖氨酸(poly-L-Lysine, PLL)和乳糖(lactose, Lac)经过常规偶联与纯化, 合成产物采用环二乙基三胺五乙酸(Diethylene triamine pentacetate acid, DTPA)法标记153Sm, 得到放射性药物Lac-PLL-DT-PA-153Sm, 并进行了家免血浆药物代谢动力学检测构建大鼠肝癌模型, 并观测Lac-PLL-DTPA-153Sm在体内的分布情况。随后将模型随机分为两组, 实验组尾静脉注入Lac-PLL-DTPA-153Sm 3.64MBq, 对照组注入Lac-PLL-DTPA。第14天处死大鼠剥离肿瘤结节, 计算肿瘤体积。
      结果  静脉注射Lac-PLL-DTPA-153Sm很快从血中分布到组织脏器中, 其血浆药物浓度半衰期T1/2为10 min结合内照射辐射计量学确定放射性药物的给药剂量为: 1 091 MBq, 与对照组比较, Lac-PLL-DTPA-153Sm确实可以引起肿瘤缩小(P < 0.01), 而对肝功能无明显影响。
      结论  此方法治疗肝癌安全有效, 为临床晚期肝癌的治疗提供了一种新方法, 值得进一步研究。

     

    Abstract:
      Objective  To investigate the feasibility of 153Sm as an internal irradiation agent for the treatment of liver cancer using a targeted lactosylated poly-L-lysine(Lac - PLL) vehicle.
      Methods  Poly-L-lysine(PLL) and lactose(Lac) were purified and labeled with 153Sm using the diethylene triamine pentaacetic acid(DTPA) method.The final product was Lac-PLL-DTPA-153Sm.Plasma pharmacokinetic detection was performed in rabbits.A rat hepatoma model was constructed, and the in vivo distribution of the radiopharmaceutical agent was also observed.Then, 3.64 MBq Lac-PLL-DTPA-153Sm was used to treat 10 rats with liver cancer through intravenous injection.Another 10 rats with liver cancer received only Lac-PLL-DTPA as the control.The volume of the tumors was measured on the 14th day after injection.
      Results  Lac-PLL-DTPA-153Sm was injected intravenously into the rats and was quickly distributed among the tissues and organs.The plasma half-life of Lac-PLL-DTPA-153Sm was 10 minutes.The single photon emission computed tomography result showed that the radiopharmaceutical agent was mainly in the liver and the tumor.The dosage was confirmed to be 1091 MBq / 3μg / 2 mL through internal exposure radiation metrology.Compared with the control group, the Lac-PLL-DTPA-153Sm treatment caused tumor shrinkage(P < 0.01).
      Conclusion  Lac-PLL-DTPA- 153Sm is a safe and effective treatment for advanced hepatocellular carcinoma, and it warrants further study.

     

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