阴离子长循环脂质体在瘤鼠体内分布和反义显像  

Anionic Long Circulation Liposomes Mediated Antisense Scintigraphy in Tumor-bearing Rats

作　　者：马超[1,2] 匡安仁[1] 黄蕤[1] 唐恭顺[1] 

机构地区：[1]四川大学华西医院核医学科,成都610041 [2]青岛大学医学院附属医院核医学科

出　　处：《生物医学工程学杂志》2011年第2期233-237,共5页Journal of Biomedical Engineering

基　　金：国家自然科学基金资助项目(30700185)

摘　　要：建立乳腺癌模型,了解游离的131I-bcl-2/bcl-xlASON(FA)以及阴离子长循环脂质体包裹的131I-bcl-2/bcl-xlASON(NA)在瘤鼠体内组织分布。SD大鼠尾静脉注射N-甲基亚硝基脲溶液,诱导建立乳腺癌模型。NA和FA分别静脉注射后0.5、1、2、3、4、6、12和24 h,断头处死瘤鼠,取其组织器官测量,计算每克组织放射性计数占注入剂量的百分数(%ID/g)。计算瘤鼠肿瘤/血液或肿瘤/肌肉比值。分别静脉注射0.4 mCi NA1、31I-错配序列阴离子长循环脂质体(NS)和131I-无义序列阴离子长循环脂质体(NN)后0.5、1、2、3、6和12 h,进行瘤鼠全身前后位静态显像。MNU致瘤时间为(96±1.2)d,SD大鼠致癌率为70%(90/130),组织学类型为乳腺癌。注射后10 h,NA在瘤鼠肿瘤组织、肝和脾内的分布分别为(6.23±0.23)%ID/g、(12.00±0.26)%ID/g和(18.25±1.33)%ID/g。肿瘤/血液和肿瘤/肌肉比值分别为6.29±0.76和10.55±0.68。NA注射后10 h,肿瘤显示最佳。NS和NN注射组瘤鼠肿瘤显示不清。NA体内清除率低,体内循环时间长,肿瘤部位浓聚增加,提示NA很可能提高放射反义治疗疗效。This paper was aimed to investigate the biodistribution and ability of free 131-bcl-2/bcl-xl ASON（FA） and anionic long circulation liposomes encapsulated with 131I-bcl-2/bclxlASON（NA）,in tumor-bearing rats,to image breast cancer.We investigated the tissue distribution of NA in virgin female Sprague-Dawley（SD） rats with n-methyl nitrosourea（MNU）-induced breast cancers in situ.The percentage of the injected dose per gram（%ID/g） was calculated,with the maximum ratios of tumor to blood and tumor to muscle,after injections of NA and FA for 0.5h,1h,2h,3h,4h,6h,12h and 24h,respectively.The ability of NA to image breast cancer in tumor-bearing rats was determined using emission computed tomography（ECT）.Seventy percent（90/130） SD rats in the study developed mammary tumors after MNU injection with the average latency（NA）（96±1.2）days.The %ID/g of NA in breast cancer tissue,tumor bearing rats in liver and spleen tumor tissues after 10 hours were（6.23±0.23）%ID/g,（12.00±0.26）%ID/g and（18.25±1.33）%ID/g,respectively.The ratios of tumor to blood 6.29±0.76 and tumor to muscle 10.55±0.68 in tumor bearing rats slowly maximized at 10h post injection of NA,most probably due to the enhanced permeability and retention effect.Hence in radionuclide antisense scintigraphy,the breast cancer in rat was clearly displayed at 10h after iv administration of NA-D.However,tumors were not visualized in rats with the iv injection of NS and NN even at the delayed time.Due to the inhibition of rapid uptake of NA by the reticulo-endothelial system,NA displays valuable pharmacologic properties characterized by the enhanced accumulation in tumor.

关 键 词：阴离子长循环脂质体 放射性碘 乳腺癌 反义显像 

分 类 号：R737.9[医药卫生—肿瘤]