Ma Chao, Kuang Anren, Huang Rui, Tang Gongshun
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2011 Apr;28(2):233-7.
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/bcl-xlASON (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 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 12 h and 24 h, 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 10 h 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.
本文旨在研究游离的131I-bcl-2/bcl-xl反义寡核苷酸（FA）和包裹有131I-bcl-2/bcl-xl反义寡核苷酸的阴离子型长循环脂质体（NA）在荷瘤大鼠体内的生物分布及对乳腺癌成像的能力。我们研究了NA在经n-甲基亚硝基脲（MNU）原位诱导乳腺癌的处女雌性斯普拉格-道利（SD）大鼠体内的组织分布。分别在注射NA和FA后0.5小时、1小时、2小时、3小时、4小时、6小时、12小时和24小时，计算每克组织中注射剂量的百分比（%ID/g），以及肿瘤与血液和肿瘤与肌肉的最大比值。使用发射计算机断层扫描（ECT）确定NA在荷瘤大鼠体内对乳腺癌成像的能力。研究中70%（90/130）的SD大鼠在注射MNU后发生乳腺肿瘤，平均潜伏期（NA）为（96±1.2）天。10小时后，乳腺癌组织、荷瘤大鼠肝脏和脾脏肿瘤组织中NA的%ID/g分别为（6.23±0.23）%ID/g、（12.00±0.26）%ID/g和（18.25±1.33）%ID/g。荷瘤大鼠注射NA后，肿瘤与血液的比值为6.29±0.76，肿瘤与肌肉的比值为10.55±0.68，在注射后10小时缓慢达到最大值，这很可能是由于增强的通透性和滞留效应。因此，在放射性核素反义闪烁显像中，静脉注射NA-D后10小时，大鼠体内的乳腺癌清晰显示。然而，即使在延迟时间，静脉注射NS和NN的大鼠体内也未观察到肿瘤。由于网状内皮系统对NA快速摄取的抑制，NA表现出有价值的药理学特性，其特征是在肿瘤中积累增强。
