荷非小细胞肺癌裸鼠体内131^I-17-AAG的分布及其抗癌潜力

目的：探讨131^I-17-丙基胺基-17-去甲氧基格尔德霉素（131^I-17-AAG）在荷瘤裸鼠体内的生物学分布及其抗癌机制。方法：通过不同给药方式（131^I-17-AAG间质给药或静脉给药、Na131I间质给药对照及竞争性显像）,显像比较12只模型鼠体内分布情况,每只5.55MBq0.1mL。1周后处死取瘤,电镜和免疫组化检测细胞凋亡和Ki-67、Bcl-2蛋白表达情况,设空白对照组（n=3）。另取24只,分别通过间质或尾静脉注射131^I-17-AAG（每只1.85MBq0.1mL）,不同时间处死,取血并测主要组织脏器的放射性计数率值。结果：显像提示,间质注射131^I-17-AAG瘤体内放射性浓聚并长时间滞留,体内分布实验进一步证实;尾静脉给药瘤体内存在一定放射性摄取,药物体内清除较快;Na131I注射后迅速排出体外,无瘤内滞留;竞争性显像示瘤内摄取降低。电镜观测给药组较对照组肿瘤增长抑制显著。Bcl-2和Ki-67阳性表达率131^I-17-AAG给药组要低于对照组。不同给药组组间比较及与对照组比较差异有统计学意义,Pmax=0.004。结论：131^I-17-AAG间质给药在瘤组织内有明确药代学分布和药效学作用,可行进一步肿瘤治疗研究。

Biodistribution and anti-cancer potential of 131^I-17-AAG in NSCLC xenograft-bearing nude mice

OBJECTIVE：To study the biodistribution and therapeutic efficiency of 131^I-17-AAG in human non-small cell lung cancer（NSCLC） xenografts in mice.METHODS：In vivo imaging was performed through 131^I-17-AAG intratumoral injection or tail veil injection,Na131I intratumoral injection and the blocking imaging group,using 12 xenografts with dosage of 5.55 MBq in 0.1 mL solution per mouse.The mice were sacrificed and tumor tissues were separated.Examinations were done through electron microscopy for tumor cell apoptosis observation and through immunohistochemistry assay for Bcl-2 and Ki-67 expression,compared with blank control （n=3）.Another 24 xenografts through 131^I-17-AAG intratumoral or intravenous delivery （1.85 MBq in 0.1 mL solution per mouse） were sacrificed at different time points.The blood and major organs were obtained for radioactivity measurement.RESULTS：In vivo imaging indicated tumor retention by 131^I-17-AAG intratumoral injection persisted for a long time,evidenced by the results of biodistribution study.While tumor uptake in tail veil injection group was not obvious but with a rapid systemic clearance,and Na131I control group had a rapid radioactivity clearance without tumor retention.In the blocking group,tumor uptake decreased significantly compared with the unblocked group.131^I-17-AAG injection groups had more tumor inhibition efficacy observed by electron microscopy and lower Bcl-2 and Ki67 expression than control groups.There were statistical significance among 131^I-17-AAG groups and control groups （Pmax=0.004）.CONCLUSION：131^I-17-AAG through intratumoral injection has certain pharmacodynamic distribution and effects on tumor tissues and may have great potential for tumor therapy.