^(131)I-BDI-1在荷人膀胱癌裸鼠体内的药代动力学研究

Study on Biodistribution and Pharmacokinetic of ^(131)I-BDI-1in Nude Mice Bearing Human Bladder Carcinoma

[目的]用^(131)I标记人膀胱癌特异性单克隆抗体BDI-1,探讨其在荷瘤裸鼠体内的生物分布及药代动力学参数,为其作为膀胱癌诊断和治疗的新型靶向药物提供基础数据。[方法]用Ch-T法进行BDI-1的^(131)I标记,标记完成后,采用Sephadex G-25分离纯化,用纸层析法测定标记产物的放化纯度,经尾静脉注入到荷人膀胱癌裸鼠体内,在不同时间处死裸鼠,测定裸鼠体内生物分布,采用DAS 2.0软件计算药代动力学参数。[结果]静注后,^(131)IBDI-1主要分布于荷瘤裸鼠肝脏、脾脏、肾脏和肿瘤等组织。血液药—时曲线符合开放性二房室分布模型,其中分布相半衰期[t_(1/2(α))]为0.1693h,消除相半衰期[t_(1/2(β))]为69.315h,峰值时间t_(max)为0.033h,平均血浆清除率为67.154L/(h·kg),曲线下面积AUC_(0-t)为904.006mg/L·h^(-1);药物在肿瘤中摄取的峰时为72h。[结论]^(131)I-BDI-1在荷人膀胱癌裸鼠中具有特异的肿瘤摄取,其在血液中清除较快,而在肿瘤中具有较快的吸收半衰期及较长的清除半衰期,适合作为一种肿瘤的靶向诊断与治疗药物。

[Purpose] To investigate the biodistribution and pharmacokinetics of131I-BDI-1 in nude mice model bearing human bladder cancer,for the basic date used as a new targeted drug.[Methods] Anti human bladder carcinoma monoclonal antibodies BDI-1 was labeled with131 I by chloramine-T method to prepare131I-BDI-1 at room temperature. The radio-chemical purity was tested with paper chromatography. Nude mice bearing human bladder cancer were injected of131I-BDI-1 via tail vein. Then the mice were sacrificed at different time.Its biodistribution was analyzed. DAS 2.0 was used to calculate pharmacokinetics. [Results] The biodistribution data showed that131I-BDI-1 accumulated mainly in liver,spleen,kidney and tumor. It was indicative of a two-compartment model with the main pharmacokinetic parameters as follows ：t1/2（α）,t1/2（β）and tmaxwere 0.1693 h,69.315 h,0.033 h respectively. CL,k10,k12 and k21were 67.154L/（h·kg）,6.021h-1,1.103h-1,0.88h-1respectively. The AUC-1（0-t）was 904.006mg/L·h.The highest time tumor uptake of131I-BDI-1 was 72 h. [Conclusion]131I-BDI-1 in nude mice model bearing human bladder cancer has a specific tumor intake,and in the blood it clears up faster.The t1/2（β）and CL suggest that it could be applied in guiding diagnosis and treatment for bladder cancer.