肝癌导向治疗中三种^(131)I标记抗体的药代动力学观察  被引量:4

PHARMACOKINETICS OF THREE  ̄(131)I-LABELLED ANTIBODIES IN IMMUNOTARGETING OF HEPATOCELLULAR CARCINOMA

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作  者:汤文英[1] 汤钊猷[1] 李君[1] 曾昭冲[1] 刘康达[1] 

机构地区:[1]上海医科大学肝癌研究所

出  处:《上海医科大学学报》1994年第4期289-292,共4页Journal of Fudan University(Medical Science)

摘  要:作者对131I标记铁蛋白多克隆抗体(131I-FtAb)、抗人肝癌单克隆抗体(131I-Hepama-1McAb)和乙型肝炎病毒X蛋白单克隆抗体(131I-HBxMcAb)的药代动力学进行研究。结果:(1)裸鼠人肝癌模型,131I-FtAb分别经静脉(iV)、腹腔(ip)途径给药,其药代动力学模式有很大差异,相同剂量的FtAb与HBxMcAb经ip给药,tmax分别为8.1h和8.4h,T1/2分别为40.5h和43.2h;不同剂量T的131I-HBxMcAb,低剂量组与高剂量组tmax分别为14.2h和8.4h,T1/2分别为36.1h和40.5h,两者有差异;(2)肝细胞癌病人:分别经动脉(ia)、ip给药后的131I-FtAb的药代动力学均为二室模型,T1/2α分别为9.3h和11.6h,T1/2β分别为56.7h和54.1h;相同剂量的131I-FtAb与131I-Hepama-1McAb经ia注射后其药代动力学模型均为二室,T1/2α分别为9.3h和5.0h,T1/2β分别为56.7h和40.6h提示:131I-FtAb具有与131I-Hepama-1McAb相似或较优的动力学特征,FtAb仍不失?In the present study, the pharmacokinetics of 131I labelled anti-hepetocellular carcinoma ferritin antibody, anti-HCC Hepama-1 monoclonal Ab (Hepama-1 AcAb), and anti-Hepatitis B virus X protein McAb (antiHBx McAb) were studied. (1) In nude mice bearing HCC. (a) The pharmacokinetics of 131I-FtAb given intravenously (iv) was significantly different from that given intraperitoneally (ip). The mean plasma clearance half-life was 53.7 hr and 40.5 hr,respectively. (b) With the same dose and ip abministration, the pharmacokinetics of FtAb and HBx McAb were similar, tmax was 8.1 hr and 8.4 hr, the mean plasma clearance half-life (T1/2) was 40.5 hr, and 43.2 hr, respectively. (C)intraperitoneal 131I-HBx McAb injection produced different plasma clearance values for higher and lower doses, T1/2 was 36 .1 hr, and 40.5 hr, tmax. was 14.2 hr and 8.4 hr, respectively. (2) In HCC patients (a) Both intraarterial (ia) or ip injection of 131I-FtAb,conformed to a two-compartmental open pharmacokinetic model, the α phase clearance half-life (T1/2α) was 9.3 hr and11.6 hr, the βphase clearance half-life (T1/2β) was 56.7 hr, and 54.1 hr,respectively. (b) After ia injection of the same dose, the plasma clearance of 131I-Hepama-1 McAb was quicker than that of 131I-FtAb. The biphasic kinetics fitted a two-compartmental pharmacokinetic model and the T1/2β was 56.7 hr and 40.6hr, respectively.In summary, this study suggests that (a) FtAb and Hepama-1 McAb show similar pharmacokinetic characters, and FtAb remains an acceptable selection for HCC targeting. (b) The Pharmacokinetics of labelled Ab may be influened by many factors, such as the antigens to be targeted, intact Ab, Ab dose, coupling methods, the method of administration and the animal for studying.

关 键 词:药代动力学 肝细胞癌 免疫疗法 

分 类 号:R735.705[医药卫生—肿瘤]

 

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