摘要
目的探讨131I-美妥昔单抗联合动脉化疗栓塞（TACE）治疗原发性肝癌（HCC）的药代动力学。方法15例肝癌患者巴塞罗纳临床肝癌分期（BCLC、B期7例、C期8例），经肝动脉注入131I-美妥昔单抗（27．75NBq／kg），间隔20min后再注入混合化疗药物的碘化油乳剂。1计数仪测量注射药物后5min和0．5、2．0、4．0、24．0、48．0、72．0、120．0、168．0h血清和尿液的放射性浓度，拟合血液药物放射性-时间曲线，残数法计算药物动力学参数和尿液药物清除速率。用SPECT行4次不同时间的全身扫描，使用ROI图像处理法计算肝肿瘤与非肿瘤组织放射性比值（T／NT），依据医学内照射辐射剂量学方法计算器官的内照射吸收剂量，采用重复测量资料的方差分析对患者体内不同时间各组织器官之间的131I-美妥昔单抗分布以及T／NT值进行统计检验。结果131I-美妥昔单抗联合TACE治疗HCC的药代动力学符合二室开放模型，药物体内吸收半衰期（t1/2a）为（1．96±1．65）h，分布半衰期（t1／20t）为（19．07±5．91）h，消除半衰期（t1/2／2B）为（57．09±10．92）h，血药峰值浓度（Cmax）为2．113×10^9min^1·L^-1，血液药物放射性-时间曲线下面积（AUC0-∞）为1．302×10^11h·min^-1·L^-1用药1周累积尿排泄放射性占注入剂量的52．2％。患者体内不同时间各组织器官之间的131I-美妥昔单抗分布以及T／NT值差异有统计学意义（F值分别=6．583、3．546，P值均〈0．01）；器官放射性分布主要浓聚于肝区肿瘤组织，心脏和脾脏等其他组织分布少。肝脏T／NT值呈逐渐减少趋势，3h为2．88±1．02，至168h为1．64±0．40。器官吸收剂量分别为肝脏（3．19±1.01）Gy，红骨髓（0．55±0．09）Gy。结论131I-美妥昔单抗联合TACE治疗HCC可提高131-美妥昔单抗的肿瘤靶向性，保证患者的辐射安全。
Objective To study the pharmacokinetics of 131I-Metuximab injection （Licartin） combined with transarterial chemoembolization （TACE） for treatment of hepatocellular carcinoma （ HCC ）. Methods Licartin （27. 75 MBq/kg） and the mixture of anticancer drug and Lipiodol were sequentially administered with interval of 20 minutes to 15 patients with HCC via a transfemoral catheter. After the Licartin was administrated, the pharmacokinetic and biodistribution data were evaluated through venous blood samples,urine collections, and 4 γ-scintigraphies （SPECT） over 7 days. The pharmacokinetic parameters were determined from integration of the blood radioactivity-time curves using the SPSS 12.0 software. The tumor-no-tumor ratio （T/NT） was calculated by ROI. Absorbed doses in organ were estimated according to the medical internal radiation dose formalism. The biodistribution of licartin within patient＇s body at different time points was compared for various organs using analysis of variance for repeated measures, as well as the T/NT ratio. Results The blood radioactivity-time curves followed the dynamics two-compartment model, with the major pharmacokinetic parameters including t1/2α （1.96 ± 1.65 ） h, and t1/2α （19. 07 ±5.91 ） h, and t1/2α （57. 09 ± 10. 92） h, and Cmax 2. 113 × 10^9min^-1 ·L^-1, and AUC0-∞ 1. 302 × 10^11 ·min^-1 ·L^-1, respectively. The accumulated urine radioactivity was 52. 2% of administrated dosage during 144 h after administration. There were statistical significant difference of biodistribution of licartin and T/NT ratio between organs at different time points （ F = 6. 583, P 〈 0. 01 and F = 3.546, P 〈 0. 01 ）. SPECT scans showed the significant accumulation of the radioconjugate in liver tumor and faint uptake in other organs for 14 days. Tumor-to-liver ratio decreased from 2. 88 ± 1.02 at 3 h to 1.64 ± 0. 40 at 168 h （ n = 7 ）. Organ absorbed dose was （3.19±1.01） Gy in liver （n =12） and （0.55 ±0.09） Gy in red marrow （n =7�
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2010年第1期74-78,共5页
Chinese Journal of Radiology
关键词
碘放射性同位素
抗体
单克隆
癌
肝细胞
肿瘤治疗方案
药代动力学
Iodine radioisotopes
Antibodies, monoclonal
Carcinoma, heptaocellular
Antineoplastic protocols
Pharmacokinetics
