^(131)碘肿瘤细胞核人鼠嵌合单抗药代动力学研究

Pharmacokinetics of Iodine-131-labeled Chimeric Monoclonal Antibody in Lung Cancer Patients

目的 :研究13 1碘肿瘤细胞核人鼠嵌合单抗 ( 13 1I chTNT)的药代动力学。方法 :9例肿瘤患者 ,体重5 0± 6kg,单次静脉推注13 1I chTNT 2 9 6± 3 7MBq/kg后测量各时间点血、尿样本中药物的放射性。应用高效液相色谱法检测13 1I chTNT在体内的稳定性和代谢情况。采用连续显像法估算各时间点全身及各器官的放射性 ,并将原始数据转换为注入剂量的百分率 (ID ,% )。结果 :72h内血清原形13 1I chTNT超过 95 %、16 8h为 ( 86±6 ) %。血清药 时曲线符合静脉给药二室模型 ,t1/2α4 93± 9 36h ,t1/2 β6 1 7± 2 1 2h ,AUC 2 9 1± 11 6MBq·h·ml-1,CL 5 3 9± 2 4 6ml/h。13 1碘是13 1I chTNT的代谢产物 ,1周累积经尿液排出注射剂量的 ( 33± 9) %。注射13 1I chTNT后放射性主要集中在肺、肝、肿瘤组织 ,脑组织最少 ,甲状腺放射性多逐渐浓聚。肿瘤组织放射性 2 4h达到最大值 ,T/L(瘤 /非瘤 )值呈逐渐增大的趋势多在 3～ 7d达到最大值 ( 1 2 5～ 3 73)。肿瘤组织 2 4 ,72 ,16 8h的ID值分别为 ( 2 8± 2 0 ) %、( 1 9± 1 3) %和 ( 0 9± 0 6 ) %。结论 :13 1I

AIM:To investigate pharmacokinetics of a mouse human chimeric monoclonal antibody (chTNT) The pharmacokinetics and distribution of the 131 I chTNT were evaluated in 9 patients weighted (50±6)kg with lung cancer METHOD: A single intravenous dose of (29 6±3 7)MBq/kg was administered Blood samples were drawn at different time intervals,and urine was collected for up to one week HPLC was established to determine the stability of 131 I chTNT in the serum,and to analyze the metabolite of 131 I chTNT Tissue distribution was followed for up to one week by gamma camera imaging The geometric mean of the anterior and posterior counts was obtained from selected ROIs to determine activity within the critical organs after subtracting the background activity RESULT: 131 I chTNT was the major component of the radiolabel in the serum,and its radioactivity was more than 95% of the radiolabel within 72h,and remaining (86±6)% at 168 h Disposition of 131 I chTNT follows a two exponential model,t 1/2α (4 93±9 36)h and t 1/2β (61 7±21 2) h ? 131 Iodine was one of the metabolites of 131 I chTNT The radioactivity (33±9)% appeared in the urine within 168 h of administering 131 I chTNT The presence of radioactivity in the liver and lungs was noted As blood pool activity in the whole body,liver,lungs decreased,tumors and thyroid activity became relatively more prominent The maximum of tumor to lung ratio of 131 I chTNT was ranged from 1 25 to 3 73 The percent of injected dose of antibody of tumor was (2 8±2 0)% at 24 h after injection,(1 9±1 3)% at 72 h and (0 9±0 6)% at 168 h CONLUSION: Pharmacokinietics of 131 I chTNT follows a two exponential model