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[摘要]
目的:〖对偶联苦瓜毒素(MT) 后131 I-BDI-1在荷瘤裸鼠体内分布与代谢性能变化进行研究,探讨其应用于膀胱癌导向治疗的可能性。方法: MT与BDI-1通过异型双功能交联剂SPDP进行偶联;BDI 1与BDI 1-MT采用ChT法进行131 I标记;两组荷人膀胱癌裸鼠分别经尾静脉注射131 I-BDI-1-MT与131 I-BDI-1,经48 h, 72 h及120 h后进行体内放射性分布测定与γ显像。计算肿瘤与各个脏器的摄取百分数(%ID/g)及与正常组织放射性之比(T/NT)。结果:与131 I-BDI-1 相比,131 I-BDI-1-MT在肿瘤中的摄取率未见明显降低,但在多数正常组织中的摄取率显著低于131 I-BDI-1,其T/NT值明显高于131 I-BDI-1;131 I-BDI-1-MTγ影像中肿瘤与正常组织的对比度优于131 I-BDI-1;131 I-BDI-1-MT与131 I-BDI-1在肿瘤中清除速率差异不大,而131 I-BDI-1-MT在正常组织中(尤其在血液中)的清除速率高于131 I-BDI-1。结论:131 I-BDI-1-MT有抗肿瘤活性,可有效地靶向膀胱癌细胞。
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[Abstract]
Objective: To investigate the possibility of radiolabelled immunotoxin BDI-1-MT used as bladder cancer guiding therapeutic agent, the biodistribution and metabolism of 131 I-BDI-1-MT in nude mice bearing human bladder carcinoma xenografts were studied.Methods:Monoclonal antibody BDI-1 was coupled with momordin (MT) by bifunctional agent SPDP. BDI-1 and BDI-1-MT were labeled with 131 I using ChT method. Nude mice with human bladder carcinoma BIU-87 xenografts were divided into two groups-131 I-BDI-1-MT group (10 mice) and 131 I-BDI-1 group (10 mice). In one mouse for each group, 629 MBq 131 I BDI-1-MT or 131 I BDI-1 was intravenously injected and γ imaging was performed 48 h, 72 h and 120 h postinjection. In other nine mice for each group, 0.74 MBq 131 I-BDI-1-MT or 131 I-BDI-1 was injected and biodistribution was measured at 48 h,72 h and 120 h postinjection respectively (3 mice at a time point ). The percent uptake dose per gram of tissues (%ID/g) and tumor over non-tumor radioactivity ratio (T/NT ) were calculated. Results:There was no significantly decrease in tumor uptake of 131 I-BDI-1-MT comparing with 131 I-BDI-1. The uptake of 131 I-BDI-1-MT in most of normal tissues was lower than that of 131 I-BDI-1, so T/NT values of 131 I-BDI-1-MT were higher than that of 131 I-BDI-1. The kidney uptake of131 I-BDI-1-MT was higher than that of 131 I-BDI-1. Tumor image could be seen 48 h postinjection for both 131 I-BDI-1-MT and 131 I-BDI-1 and got more clear with time lasted. But the image contrast of 131 I-BDI-1-MT was better than that of 131 I-BDI-1. There was no obvious difference in clearance rate of 131 I-BDI-1-MT and 131 I-BDI-1 in tumor. The clearance rate of 131 I-BDI-1-MT in normal tissues was significantly higher than that of 131 I-BDI-1 especially in blood. Conclusion: It demonstrated that 131 I-BDI-1-MT can effectively target to bladder cancer cells.
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