抗人活化血小板嵌合单克隆抗体SZ-51/Hu的纯化、鉴定和核素标记  

Purification,Characterization and Nuclide Labeling of A Chimeric McAb(SZ-51/Hu)Specific for Human Activated Platelets

作　　者：张玮[1] 阮长耿[1] 

机构地区：[1]苏州大学附属第一医院血栓与止血研究室,江苏省血液研究所,苏州215006

出　　处：《苏州医学院学报》2001年第3期244-247,共4页Acta Academiae Medicinae Suzhou

基　　金：国际原子能机构(IAEA)部分资助课题(CPR/06/02)

摘　　要：目的　评价抗人活化血小板嵌合单克隆抗体SZ - 5 1/Hu核素标记及其用于临床血栓放射免疫显像的可行性。方法　用免疫亲和层析法纯化SZ - 5 1/Hu ,并对其特性进行鉴定 ,以过量的 2 -亚氨硫醇预处理SZ - 5 1/Hu ,采用99Tcm-葡庚糖酸钠 (GH)配体交换法标记。薄层层析法测定标记物的放化纯度。制备实验性狗股动脉血栓模型后 ,经静脉注入99Tcm-SZ - 5 1/Hu进行SPECT显像。结果　纯化的SZ - 5 1/Hu分子量为 16 0kD ,亲和常数 5 .5 10 4× 10 8L/mol,每个活化血小板的结合位点数平均为 10 2 6 2± 2 372个。99Tcm 抗体的标记率达 96 %以上。实验性狗股动脉血栓模型注射99Tcm-SZ - 5 1/Hu后 4h血栓显示清晰。结论　SZ - 5 1/Hu保留了原鼠源单抗SZ- 5 1/Hu相同的活化血小板 (GMP - 140 )结合特异性和亲和力。99Tcm 标记后仍保持良好的体内特异性血栓定位能力 ,可望用于临床血栓放射免疫显像。Objective To evaluate the mouse/human chimeric McAb SZ-51/Hu labeled with a nuclide and the feasibility of its application in radioimmunoimaging.Methods Purification of SZ-51/Hu was performed by affinity chromatography,and then its characteristics were analyzed.SZ-51/Hu was labeled by using the method of 2-iminothiolane modification and 99 Tc m -glucoheptonate(GH) transchelation.The radiochemical purity was determined by I.T.L.C-SG.The experimental formal arterial thrombus was prepared in canine,then 99 Tc m -SZ-51/Hu was injected intravenously and imaged by SPECT.Results The molecular weight of SZ-51/Hu was 160KD.Its affinity constant was 5.5104 ×10 8L/mol and the number of binding molecular of SZ-51/Hu in per sactivated platelet was 10262±2372.The labeling efficiency was more than 96%.The arterial thrombus was clearly discernible at 4 hours after injection of 99 Tc m -SZ-51/Hu in the canine experimental model of femoral arterial thrombosis.Conclusion SZ-51/Hu retains the similar binding characteristics in vitro and thrombus-targeting in vivo as that of murine McAb SZ-51.Therefore,SZ-51/Hu may be a potential agent for clinical diagnosis thrombotic disease.

关 键 词：活化血小板 嵌合单克隆抗体 纯化 ^(99)Tc^(m) 标记 

分 类 号：R392.11[医药卫生—免疫学] R817.4[医药卫生—基础医学]