磁共振检测纳米磁靶向性药物在荷瘤小鼠体内分布的初步研究

Preliminary Study of the Distribution of Target Magnetic Nanoparticles in Mice Measured by Magnetic Resonance Image In Vivo

目的利用MRI技术探讨活体状态磁靶向性药物在荷瘤小鼠体内的分布。方法取荷瘤裸鼠24只随机分为3组,每组8只。A组为空白对照组,经尾静脉注射生理盐水0.2ml;B组未建立局部磁场,单纯静脉注射纳米磁小体靶向氟脲嘧啶药囊(剂量250mg/kg);C组为建立肿瘤局部内磁场后静脉注射纳米磁小体靶向氟脲嘧啶药囊(250mg/kg)。三组每天用药一次,连续5天。在最后一次用药后24h,每组各取2只动物行MRI扫描,扫描完毕后处死荷瘤鼠,取肝、肾、脑和肿瘤组织作病理学检查。结果与A组比较,B和C组中T1WI和T2WI上肝、肾组织信号都明显降低,以肝脏降低更显著;与A和B组比较,C组中肿瘤信号在T2WI上明显降低;3组中,脑组织信号均无明显变化。病理学检查也进一步证实。结论磁性药物主要通过肝、肾代谢,在建立肿瘤局部内磁场后,磁性药物可以靶向性分布于肿瘤,磁性药物不能通过血脑屏障。MRI技术是检测磁靶向性药物在活体荷瘤小鼠体内分布的有效方法。

Objective： To investigate the distribution of target magnetic nano-particles in mice by MRI. Methods：24 nuke mouse bearing tumor as animal models were randomly divided into 3 groups,8 mouse for each group. Group A received placebo （sodium chlonide） 0.2ml administered via tail vein; group B received magnetic nanopartieles with 5-Fu capsules administered intravenously at 250mg/kg on consecutive five days without application of magnetic fields; group C consist of magnetic fields built inside tumor tissue and received the same medicine as group B. 24 hours after 5 days＇ consecutive administration of medicine,two mouse of each group selected at random were examined on MRI T1WI and T2WI, and were sacrificed afterwards. Tissues of liver, kidney, brain and tumor were taken for pathology study. Results：On T1WI and T2WI, the signal intensities of liver and kidney in group B and group C were obviously decreased when compared with that in group A; which was more marked in liver. On T2WI, the signal intensities of tumor tissue in group C was significantly lower than that of group A and B. No marked variation was revealed in brain tissue of all these three groups. Further pathology examination proved high concentration of ferric ion within tumor tissue of group C. Conclusion： Metabolism of magnetic nano-particles is mainly located within liver and kidney. After building up the intra-tumoral magnetic field, the magnetic particles could be distributed within the target tumor. Magnetic particle cannot pass through blood brain barrier. MRI is an effective technique in defining the distribution of magnetic nanoparcticles in nude mice in vivo.