^(35)S标记SZ39导向治疗胶质瘤的实验研究

An experimental study of targeting therapy with 35 S SZ39 against glioma

目的制备纯β射线放射免疫治疗制剂３５Ｓ标记单克隆抗体（ＭＡｂ）ＳＺ３９，并证实其对胶质瘤的特异杀伤作用。方法３５Ｓ以碳二亚胺法标记ＳＺ３９。采用ＭＴＴ法，以人脑胶质瘤细胞系ＳＨＧ４４为靶细胞，检测３５ＳＳＺ３９及其对照组３５ＳｎＩｇＧ、３５Ｓ加ＳＺ３９、３５Ｓ持续作用组的细胞杀伤率，求得５０％细胞抑制浓度；以荷瘤鼠为对象，以３５ＳｎＩｇＧ及ＰＢＳ为对照组，根据公式求得３５ＳＳＺ３９肿瘤抑制率；并以流式细胞计数仪分析３５ＳＳＺ３９的抑瘤效应。结果３５ＳＳＺ３９细胞杀伤力与３５Ｓ持续作用相近，较３５ＳｎＩｇＧ强４２倍，较３５Ｓ加ＳＺ３９强４０倍。１０３６ＭＢｑ３５ＳＳＺ３９对肿瘤可产生抑制作用，阻滞肿瘤生长１周左右，给药后２６ｄ，抑制率达５０％。经３５ＳＳＺ３９治疗后肿瘤细胞ＤＮＡ合成受抑，Ｓ期细胞蓄积，Ｇ１期细胞受阻，有细胞周期同步化趋势。３５ＳＳＺ３９有抑瘤作用，但对骨髓无明显毒副作用。结论３５ＳＳＺ３９能选择性杀伤胶质瘤细胞。

Objective To prepare a pure β emitting immunoradiotherapeutic agent 35 S MAb SZ39, and validate its special therapeutic efficacy against glioma Methods MAb SZ39 was labelled with 35 S using a carbodiimide method Using 35 S nIgG, 35 S+MAb SZ39 and sustained 35 S as control agents, and human brain glioma cell line SHG 44 as target cell, the injury rate and 50% inhibitory concentration of 35 S MAb SZ39 were evaluated with MTT method 35 [KG*3/5]S MAb SZ39 and its control agent 35 S nIgG or PBS were i p injected into glioma bearing nude mice The tumor inhibitory rate (I) was determined according to the formula: I= 1-(TV 35 S MAb /TV PBS ) ×100% (TV: tumor volume) Flowcytometry was used to analyse the cell cycle of glioma after treatment Results 35 S MAb SZ39 had a strong cytotoxic effect to glioma cells with 4 2 fold and 4 0 fold more toxic than 35 S nIgG and 35 S+MAb SZ39, as strong as the sustained 35 S control group Tumor growth blocking for one week was obtained with 103 6 MBq 35 S MAb SZ39 treatment The inhibitory rate was 50% 26 days after 35 S MAb SZ39 administration DNA synthesis of glioma cells was inhibited, cells were accumulated in S period and the road to G 1 period was blocked There was a trend of cell cycle synchronization No obvious toxicity was found on bone marrow while 35 S MAb SZ39 made the glioma growth block Conclusions 35 S MAb SZ39 has a strong selective injurious effect on glioma and is of good prospect to be an immunoradiotherapeutic agent