重组人纤溶酶原Kringle 5的^(125)I标记及其体内代谢  

^(125)I labeling of recombinant human plasminogen Kringle 5 and its in vivo metabolism

作　　者：尹桂芝[1] 李彪[2] 张大东[2] 张一帆[2] 赵龙[2] 尤蓓[2] 张志勇[3] 余自成[2] 于金德[2] 

机构地区：[1]上海瑞金医院集团闵行区中心医院心内科,上海201100 [2]上海瑞金医院,上海200025 [3]上海欣科医药有限公司,上海200000

出　　处：《黑龙江医药科学》2007年第1期51-53,共3页Heilongjiang Medicine and Pharmacy

基　　金：上海市科技发展基金(99JC4041)资助项目

摘　　要：目的:探讨放射性碘标记纤溶酶原Kringle 5(K 5)的生物学活性及其体内药代动力学。方法:采用基因工程方法制备重组人纤溶酶原Kringle 5(rhK 5),以小剂量Iodogen多次重复标记法标记rhK 5,细胞增殖抑制试验和亲和力试验检测125I-rhK 5活性,并研究其在大鼠体内的药代动力学。结果:125I-rhK 5的标记率为86%,放射化学纯度为96%。细胞增殖抑制试验表明,125I-rhK 5的生物活性与未标记rhK 5相当。大鼠单次股静脉注射2μg125I-rhK 5后,血药浓度-时间曲线符合两室模型,T 1/2α为(0.31±0.03)h,T 1/2β为(14.48±0.73)h,AUC为(436.58±34.6)ng.h.m-l 1。结论:小剂量Iodogen多次重复125I标记不影响rhK 5的生物学活性1。25I-rhK 5大鼠体内单次静脉注射的药代动力学符合两室模型,半衰期约为15h。125I-rhK 5为肿瘤的显像和靶向治疗奠定了基础。Objective： To study the biological activity and in vivo pharmacokinetics of ^125I labeled recombinant human plasminogen Kringle5 （^125I- rhKS）. Methods ^125I- rhK5 was prepared by small amount of iodogen with repeated labeling. Biological activity of ^125I- rhK5 was evaluated by cell proliferation assays and cell affinity assays. And pharmacokinetic parameters of ^125I-rhK5 in the SD rats were also analyzed. Results. When ^125I-rhK5 was prepared by 4μg /kg iodogen labeling,its radio purity reached 96%. The labeling rate was 86%. Cell proliferation and cell affinity assays showed the biological activity of ^125I--rhK5 was omparable to that of unlabled rhK5. After intravenous injection with a single dose of 2μg of ^125I--rhK5 to rats, the plasma concentration time curve fitted well to two--compartment model. The T1/2α= （0. 31±0.03）h,T1/2β= （14.48±0. 73）h,AUC=（436. 58±34. 6）ng ·h · ml^-1. Conclusion：Small amount of iodogen repeated ^125I labeling assay had no influence on the biological activity of rhK5. After intravenous injection with a single dose of 2μg of ^125I-rhK5 to rats,its pharmacokinetics is in correspondence with two-compartment model with half life of about 15h, suggesting ^125I-rhK5 can be used as a novel agent for cancer imaging and therapy.

关 键 词：纤溶酶原Kringle 5 ^125I标记 药代动力学 

分 类 号：R73-36[医药卫生—肿瘤] R815[医药卫生—临床医学]