SPIO标记的c-erbB2反义探针用于活体荷瘤裸鼠MRI的最佳扫描浓度  

Optimal concentration of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles for magnetic resonance imaging in tumor-bearing nude mice

作　　者：温志鹏[1] 刘海燕[1] 文明[1] 贺海容[1] 谭书德[1] 李少林[1] 

机构地区：[1]重庆医科大学附属第一医院放射科,重庆400016

出　　处：《南方医科大学学报》2013年第4期496-501,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(30940021);重庆市自然科学基金(CSTC2008BB5209);重庆市卫生局医学科研基金(062029)~~

摘　　要：目的探讨SPIO标记的c-erbB2反义寡脱氧核苷酸探针用于活体荷瘤裸鼠MRI的最佳扫描浓度。方法 BALB/c荷瘤裸鼠30只,随机分为5组并每组注射不同浓度反义探针(含Fe 6.0、9.0、12.0、15.0、18.0 mg/kg),每组裸鼠于既定的时间点(注射前、注射后360 min)同步行MRI扫描。在完成MR扫描后,立即处死荷瘤裸鼠,取出肿瘤组织,行HE及普鲁士蓝染色,光学显微镜下观察;测量肿瘤组织在注射不同浓度反义探针前后的信号强度变化。结果成功建立荷瘤裸鼠模型,成瘤率100%。6.0、9.0及12.0 mg组裸鼠注射探针后均存活,但15.0 mg组及18.0 mg组注射探针及扫描完成后存在部分裸鼠死亡;对比荷瘤裸鼠肿瘤组织在不同浓度反义探针注射前后的信号强度变化,发现12.0、15.0及18.0 mg组裸鼠在注射探针后,肿瘤组织信号强度变化更具显著性(P<0.001);肿瘤组织信号强度均明显变化并可达到明显肉眼辨识水平,在MR扫描图像上能够清楚显示,并且12.0 mg组、15.0 mg组及18.0 mg组的统计学差异无显著性(P>0.05)。HE染色发现肿瘤组织结构紊乱,存在大量异性肿瘤细胞,排列呈"癌巢"状,在各浓度组表现相似;而普鲁士蓝染色发现各浓度组的肿瘤组织标本中均散在分布斑点状蓝色铁颗粒,12.0 mg组、15.0 mg组及18.0 mg组分布均密集明显。结论 SPIO标记的c-erbB2反义寡脱氧核苷酸探针能靶向于肿瘤组织,用于BALB/c裸鼠MRI的最佳扫描浓度为含Fe 12.0 mg/kg。Objective To determine the optimal concentration of c-erbB2 antisense probe labeled with superparamagnetic iron oxide（SPIO） nanoparticles for in vivo tumor imaging in mice using magnetic resonance imaging（MRI）.Methods Thirty BALB/c mice bearing SK-Br-3 tumor were randomized into 5 groups to receive injections of different concentrations of SPIO-labeled c-erbB2 antisense probe（containing 6.0,9.0,12.0,15.0,or 18.0 mg Fe/kg）.MRI was performed before and 6 h after the injections,and the signal intensities of the tumor were compared among the groups.The tumor tissues were then dissected for microscopic examination with HE and Prussian blue staining.Results The tumor-bearing mice all survived after injections of the probe at doses of 6.0,9.0 and 12.0 mg,but injections at higher doses（15.0 and 18.0 mg） caused death in some mice. Injections of the probe at the doses of 12.0,15.0 and 18.0 mg resulted in significant signal enhancement of the tumor（P0.001） to allow visual identification,but the changes showed no significant differences among the 3 groups（P0.05）.Pathological examination revealed irregular structures of the tumor issue containing numerous heterogenous tumor cells aligned into cancer nests;Prussian blue staining visualized scattered blue iron particles in the tumor issue,which was especially obvious in mice injected with 12.0,15.0 and 18.0 mg labeled probe.Conclusion Injection of 12.0 mg/kg SPIO-labeled c-erbB2 antisense probe allows optimal tumor imaging in BALB/c mice using MRI.

关 键 词：超顺磁氧化铁 反义探针 活体动物 MRI 扫描浓度 

分 类 号：R73-3[医药卫生—肿瘤]