重组人内皮抑素的^(125)I标记及其体内代谢  

^(125)I Labeling of Recombinant Human Endostatin and Its Metabolism

作　　者：尤蓓[1] 李彪[2,3] 张一帆[2,3] 尹桂芝[1] 赵龙[2,3] 张志勇 陆林[1] 于金德[1] 余自成[5] 朱承谟[2,3] 

机构地区：[1]上海第二医科大学瑞金医院心血管科 [2]上海第二医科大学瑞金医院核医学科,上海200025 [3]上海第二医科大学临床核医学研究所 [4]上海欣科医药有限公司 [5]上海第二医科大学瑞金医院临床药理科

出　　处：《上海第二医科大学学报》2005年第12期1221-1224,共4页Acta Universitatis Medicinalis Secondae Shanghai

基　　金：上海市科技发展基金(99JC14041和014119093)资助项目.

摘　　要：目的探讨重组人内皮抑素(rhEndo)的^(125)I标记及其标记物(^(125)I-rhEndo)的生物学活性和体内药代动力学。方法采用小剂量Iodogen多次重复标记法标记rhEndo,细胞增殖抑制试验和亲和力试验检测^(125)I-rhEndo活性,并研究其在大鼠体内的药代动力学。结果0.5μg Iodogen3次重复标记rhEndo的标记率可达84%,放射化学纯度(94.7±2.44)%。^(125)I-rhEndo抑制bFGF诱导内皮细胞增殖的作用与未标记rhEndo相当,且能与其竞争结合内皮细胞表面受体。大鼠单次股静脉注射^(125)I-rhEndo2μg后,血药浓度-时间曲线符合两室模型,T1/2α为(0.45±0.12)h,T1/2β为(19.53±3.41)h,AUC为(484.57±137.99)ng·h·mL-1。结论小剂量Iodogen多次重复^(125)I标记不影响rhEndo蛋白的生物学活性。^(125)I-rhEndo大鼠体内单次静脉注射的药代动力学符合两室模型,半衰期约19h。^(125)I-rhEndo标记为肿瘤的靶向显像和治疗奠定了基础。Objective To study the biological activity and in vivo pharmacokinetics of ^125I labeled recombinant human endostatin （^125I-rhEndo）. Methods ^125I-rhEndo was prepared by small amount of iodogen with repeated labeling. Radiochemical purity （RP） was tested by paper chromatographic analysis. Biological activity of ^125I rhEndo was evaluated according to cell proliferation assays and cell affinity assays. And pharmacokinetic parameters of ^125I-rhEndo in the SD rats were also analyzed. Results ^125I-rhEndo was prepared by 0.5μg iodogen labeling thrice with its radio purity reached （94.7±2.44）%. The labeling rate was 84%. Cell proliferation assays showed no significant difference between the ^125I-rhEndo and unlabeled rhEndo on inhibition of bFGF-induced ECV304 cell proliferation. In cell affinity assays ^125I-rhEndo could bind the endothelial cell surface receptors in compitition with unlabeled rhEndo. After intravenous injection with a single dose of 2 μg ^125 I-rhEndo to rats, the plasma concentration-time curve fitted well to two-compartment model. The T1/2α = （0.45 ±0. 12） h, T1/2β = （19.53 ±3.41） h, AUC = （484.57 ± 137.99） ng· h· mL^-1. Conclusion Small amount of iodogen repeated ^125I labeling assay did not influence the biological activity of rhEndo. After intravenous injection with a single dose of 2 μg ^125I-rhEndo to rats, its pharmacokinetic was in correspondence with two-compartment model with half life about 19 h. ^125I labeling of rhEndo outlined the potential of this targeting agent for cancer imaging and therapy.

关 键 词：内皮抑素 ^125I标记 药代动力学 体内代谢 重组人内皮抑素 

分 类 号：R817[医药卫生—影像医学与核医学] R-332[医药卫生—放射医学]