肿瘤血管靶向分子探针^(131)I-RRL的辐射吸收剂量及代谢动力分析  

Radiation dose and pharmacokinetic analysis of molecular probe ^(131)I-RRL targeting tumor angiogenesis

作　　者：赵倩[1,2] 王飞[1] 王荣福[1] 闫平[1] 李娟[2] 张春丽[1] 殷雷[1] 李颖[3] 

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]宁夏医科大学总医院核医学科,宁夏银川750004 [3]北京大学第一医院药剂科,北京100034

出　　处：《中国介入影像与治疗学》2014年第3期172-176,共5页Chinese Journal of Interventional Imaging and Therapy

基　　金：国家自然科学基金(30870729;81071183);国家重大科学仪器设备开发专项(2011YQ03011409)

摘　　要：目的通过分析小鼠体内生物学分布,推算肿瘤靶向新生血管的分子探针(修饰后的RRL多肽与碘-131)131IRRL在人体主要器官内的照射吸收剂量,探讨其在日本大耳白兔体内的药代动力学特征。方法对40只荷瘤B16黑色素瘤小鼠尾静脉注射131I-RRL,之后于不同时刻处死,测定体内各脏器放射性分布,换算标准成人体131I-RRL辐射吸收剂量。对4只荷瘤小鼠注射探针后行SPECT全身显像。对5只日本大耳白兔注射131I-RRL后,于不同时刻取血,计算药代动力学参数,判断房室模型。结果注射131I-RRL初期,放射性主要分布于荷瘤小鼠双肾及膀胱,血液中放射性清除迅速;随时间延长,靶组织/非靶组织值较高;SPECT显像肿瘤组织放射性浓聚显著高于其他器官或组织,24h后仅见肿瘤内放射性聚集。成人体内照射吸收的有效剂量为0.0293mSv/MBq。兔药代动力学呈二室模型,分布相半衰期为(0.32+0.07)h,清除相相半衰期为(33.15+5.67)h。结论 131I-RRL是一种安全的显像剂,在体内吸收速度快、清除缓慢,具有较高靶组织滞留率和良好药代动力学特征,可能用于肿瘤靶向治疗。Objective To estimate the radiation absorbed doses of 131I-RRL in human being by analyzing its biologic distribution in mice, and to discuss its pharmacokinetics in big ear rabbits. Methods 131 I-RRL was injected into 40 mice via lateral tail vein, and then its biodistribution was observed in different time points, and the radiation dosimetry of 131 I-RRL in human being was calculated according to the organ distribution in mouse. Another 4 mice were used for SPECT, while 5 rabbits were used in pharmacokinetic observation. Results Early after injection of 131 I-RRL, the radioactivity in tumor- burdened mice mainly distributed in kidneys and bladder, while in blood declined quickly. With time going, the ratio of target tissue and nontarget tissue became higher in mice. SPECT showed that radioactivity in tumor tissue was higher than in other organs or tissue. Only tumor gathered radiation after 24 h. Absorption effective dose in adult body was 0. 0293 mSv/ MBq. The pharmacokinetics of rabbits was 2 room model, distribution of half-life was （0.32＋0.07）h, remove phase half- life was （33.15＋5.67）h. Conclusion 131I-RRL is a safe means of imaging agent, which has fast absorption and slow clearance speed in the body, and may be used in target therapy of tumors.

关 键 词：131I标记 RRL多肽 分子探针 辐射剂量 放射性核素显像 药代动力学 

分 类 号：R817.4[医药卫生—影像医学与核医学]