^(153)Sm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-^(153)Sm for the Treatment of Liver Cancer

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^(153)Sm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^(153)Sm,得到放射性药物Lac-PLL-DT-PA-^(153)Sm,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-★★Sm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-^(153)Sm 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-^(153)Sm很快从血中分布到组织脏器中,其血浆药物浓度半衰期T_(1/2)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-^(153)Sm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。

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 pentaaeetic 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 ＆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 Lae-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 Lae-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 1 091 MBq / 3 μg / 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-~53Sm is a safe and effective treatment for advanced hepatocellular carcinoma, and it warrants further study.