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[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。
[Objective] To investigate the biodistribution and pharmacokinetic parameters of BDI-1 in human bladder cancer with ~ (131) I as a new type of bladder cancer diagnosis and treatment Targeted drugs provide basic data. [Method] The ~ (131) I labeling of BDI-1 was performed by Ch-T method. After the labeling was completed, it was separated and purified by Sephadex G-25. The radiochemical purity of the labeled product was determined by paper chromatography. In nude mice bearing human bladder cancer, nude mice were sacrificed at different times and the biodistribution in nude mice was measured. The pharmacokinetic parameters were calculated using DAS 2.0 software. [Results] After intravenous injection, ~ (131) IBDI-1 mainly distributed in liver, spleen, kidney and tumor in nude mice bearing tumor. The blood drug-time curve was in accordance with the open two-compartment distribution model, in which the distribution phase half-life [t 1/2 (α))] was 0.1693 h and the elimination half-life [t 1/2] was 69.315 h, The peak time t max was 0.033 h, the mean plasma clearance was 67.154 L / (h · kg), and the area under the curve was 904.006 mg / L · h -1 Peak intake 72h. [Conclusion] ~ (131) I-BDI-1 has specific tumor uptake in nude mice bearing human bladder cancer, which has a faster clearance in the blood and a faster absorption half-life and a longer elimination half-life in the tumor , Suitable as a tumor targeted diagnosis and treatment of drugs.