胃癌免疫脂质体导向硼中子俘获治疗的实验研究

Boron Neutron Capture Therapy Mediated by Immunoliposomes Against Human Gastric Cancer

本文报告应用胃癌免疫脂质体包裹同位素^(10)B进行胃癌硼中子俘获治疗(BNCT)的初步研究。H_3 ^(10)BO_3和(Et_4N)_2^(10)B_(10)H_(10)分别包入脂质体,连接抗人胃癌单克隆抗体MGb_2,包裹率分别为5.3％和8.2％,平均每一脂质体可包入7.5×10_4和1.2×10_5个^(10)B原子,结合50分子抗体。免疫荧光和ELISA证实抗体活性保持80％～90％。两种免疫脂质体对胃癌细胞KATO Ⅲ的结合达7.6×10~9和5.5×10~9 ^(10)B/细胞,是正常细胞的23和27倍,均达到BNCT所需浓度(1×10_9 ^(10)B/细胞)。直接包裹^(10)B原料H_3^(10)BO_3,降低了成本。结果表明,制备的免疫脂质体对^(10)B具有较好的导向作用,可能用于胄癌的硼中子俘获治疗。

The theoretical basis for boron neutron capture therapy (BNCT) derivesfrom the neuclcur reaction which yields Li-7 and alpha particals with high energy: 510B +01 n→37Li + 24He + 2.79MeV. Success of BNCT depends upon localizing asufficient amount of boron-10 at the site of tumor (20-30 μg/g of tumor). Immunolipo-somes against human gastric cancer were prepared by encapsulating boron-10 compounds for BNCT. B3 10BO3 and (Et4 N)2 10B10H10 were entrapped in 100 nm liposomes coating the monoclonal antibody MGb2 against human gastric cancer. Immunoliposomes were prepared by reverse-phase evaporation and palmitoyled antibody incorporation method. Boron concentrations were determined by ICP-atomic emission Spectrometry There were 7.5×104 and 1.2×105 boron -10 atoms entrapped and 50 antibodies incorporated per one liposome. Immunofluorescent staining and ELISA indicated that the immunoreactivity of antibodies on liposomes was well preserved (80%-90%). The two kinds of immunoliposomes both showed prefered binding to human gastric cancer cell line KATO III as much as 126 and 92 μg/g, respectively. Meanwhile, the binding to normal human embryonic lung cell line SL7 was only 1/23 and 1/27 of that to tumor cells. Much cheaper material H310BO3 was entrapped directly in liposomes, making the method more practical. The results demonstrated that the boron-10 containing immuno-lipo somes could deliver adequate amount of boron-10 selectively to the target tumor cells and might be useful in boron neutron capture therapy of gastric cancer.