SPIO-shRNA分子探针用于荷瘤裸鼠MR检查的最佳扫描浓度探讨

Optimal scanning concentration of MR imaging for tumor-bearing nude mice with SPIO-shRNA molecular probe

目的:探讨SPIO-shRNA分子探针在活体荷瘤裸鼠肿瘤区域组织信号的变化情况,阐明分子探针用于荷瘤裸鼠的最佳扫描浓度。方法:将30只BALB/c荷瘤裸鼠随机分为5组,每组6只,在既定扫描时间(探针注射前及注射后27 h)分别以含铁量为6、12、18、24、30 mg·kg^(-1)尾静脉注射并同步行MR检查,测量肿瘤组织及对侧对应区域肌肉组织在各浓度组的信号强度变化。每次检查完成后立即处死裸鼠,取肿瘤组织及肌肉组织行HE及普鲁士蓝染色,并在光镜下观察。结果:6、12、18 mg·kg^(-1)组裸鼠探针注射后均存活,24、30 mg·kg^(-1)组探针注射后及扫描过程中出现部分裸鼠死亡;各浓度组间肿瘤组织体积差异无统计学意义(P>0.05);MR各扫描序列以T_2WI及T_2*序列的信号改变最明显;各浓度组比较,肿瘤组织信号强度在18、24、30 mg·kg^(-1)组较其余组差异明显(P<0.05),而18、24、30 mg·kg^(-1)组间差异无统计学意义(P>0.05);HE染色显示肿瘤组织结构紊乱,细胞核异型性较多;普鲁士蓝染色表明不同浓度组肿瘤组织中均存在蓝染的铁颗粒,其中18、24、30 mg·kg^(-1)组蓝染颗粒分布密集。结论:SPIO-shRNA分子探针能成功靶向于肿瘤组织,且最佳扫描浓度(含铁量)为18 mg·kg^(-1)。

Objective： To investigate MRI signal variation and the optimal scanning concentration for tumor-bearing nude mice with SPIO-shRNA molecular probes.Methods： Thirty BALB/c tumor-bearing nude mice were randomly divided into five groups with 6 in each group.Iron content of6, 12, 18, 24, 30 mg·kg-1was administered respectively through tail vein injection and simultaneously MR examination was performed to measure signal intensity in tumor tissue and contralateral muscle tissue.After treatment, the nude mice were sacrificed and tumor and muscle tissues were sampled for HE and Prussian blue stain.Results： Groups with 6, 12 and 18 mg·kg-1 were all survived after probe injection, but some nude mice died in 24 and 30 mg·kg-1 groups after injection or during scanning process.There was no significant difference in tumor tissues volume between the groups.The most marked signal changes were T2WI and T2＊GRE and the signal intensity of the tumor tissue in 18, 24 and 30 mg·kg-1 groups were most obvious（P＆lt;0.05）, while the 18, 24 and 30 mg·kg-1 groups showed no statistical difference（P〉0.05）.HE staining indicated disorganization of tumor tissue as well as marked cell nuclear atypia.Prussian blue staining showed that iron particles were distributed dispersedly in each experimental group, and the most abundant expressions were in 18, 24 and 30 mg·kg-1 groups.Conclusion： Tumor tissue could be well labeled with SPIO-shRNA molecular probes, and the optimal MR scanning concentration is 18 mg·kg-1.