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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 investigate the biological activity and pharmacokinetics of ~ (125) I in recombinant human endostatin (rhEndo) and its biomarker (~ (125) I-rhEndo). Methods A small dose of Iodogen repeated labeling method labeled rhEndo, cell proliferation inhibition test and affinity test for detection of 125 I-rhEndo activity, and to study its pharmacokinetics in rats. Results 0.5 μg Iodogen3 repeated labeling rhEndo labeling rate of up to 84%, radiochemical purity (94.7 ± 2.44)%. The effect of ~ (125) I-rhEndo on bFGF-induced endothelial cell proliferation was comparable to that of unlabeled rhEndo, and competed with it for binding to endothelial cell surface receptors. After a single intravenous injection of ~ (125) I-rhEndo2μg into rat, the plasma concentration-time curve accorded with the two-compartment model with T1 / 2α of (0.45 ± 0.12) h and T1 / 2β of (19.53 ± 3.41) (484.57 ± 137.99) ng · h · mL-1. Conclusions The small dose of Iodogen multiple repeat 125 I labeling does not affect the biological activity of rhEndo protein. The pharmacokinetics of ~ (125) I-rhEndo in a single intravenous injection were in accordance with the two-compartment model with a half-life of about 19 h. ~ (125) I-rhEndo labeling for tumor targeted imaging and treatment laid the foundation.