MR成像活体示踪SPIO-shRNA分子探针的生物分布

Magnetic Resonance Imaging Tracing the Biodistribution of SPIO-shRNA Molecular Probe in vivo

目的探讨磁共振成像(MR成像)能否示踪超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)-shRNA分子探针在活体动物主要脏器的生物分布。方法 6只新西兰大白兔,注射SPIO-shRNA分子探针(含铁量为9.6mg/kg),原子吸收光谱法(atomic absorption spectrometry,AAS)测量注射前30 min及注射后1 min、3min、5min、10min、15min、30min、1h、2h、3h、6h、12h、24h的血浆铁质量浓度以分析其药代动力学。6只昆明(KM)小鼠于尾静脉注射含铁量为4.8mg/kg的SPIO-shRNA分子探针,MR成像活体示踪探针在小鼠体内主要脏器的生物分布。96只KM小鼠于未给药及给药后1d、3d、5d、7d、9d、11d、14d,取肝、脾、肾、脑及肌肉组织,AAS测定各脏器组织探针铁含量,同时行普鲁士蓝染色并与MR结果对照分析。结果本探针的药代动力学符合二室模型,半衰期为(3.692±0.196)h。MR显示探针在正常小鼠体内主要分布于肝脏与脾脏,代谢缓慢,于2周左右完全从肝、脾代谢清除;AAS对脏器探针铁含量的测定与普鲁士蓝染色证实了MR成像结果。结论本研究明确了MR成像可用于活体示踪SPIO-shRNA分子探针在动物体内主要脏器的生物分布,为进一步利用MR无创监测探针在动物体内的治疗作用提供了依据。

Objective To investigate the biodistribution of superparamagnetic iron oxide（SPIO）-shRNA molecular probe by magnetic resonance imaging（MRI）in vivo.Methods Six New Zealand white rabbits were injected intravenously with SPIO-shRNA molecular probe（9.6 mg Fe/kg）via ear edge vein.The blood samples were collected to analyse the pharmacokinetic parameters through measuring the iron content by atomic absorption spectrometry（AAS）method at 30 min before and 1min,3min,5min,10 min,15min,30 min and at 1,2,3,6,12,and 24 hafter the injection.Six Kun Ming（KM）mice were injected intravenously with SPIO-shRNA molecular probe（4.8mg Fe/kg）.The biodistribution of SPIO-shRNA molecular probe was traced by MRI in vivo.Ninety six KM mice were randomly divided into control group and experimental group：each mouse in experimental group was injected intravenously with SPIO-shRNA molecular probe（4.8 mg Fe/kg）.The liver,spleen,kidney,brain and muscle of the control group and the experimental group on 1,3,5,7,9,11 and 14dafter the injection were collected.The organ iron content were measured by AAS method and Prussian blue staining in order to observe the distribution of the SPIO-shRNA molecular probe in the main organ.Results Our results demonstrated that the pharmacokinetics of the molecular probe complied with two-compartment model,and the blood half-life was（3.692±0.196）h.The data of MRI showed that the probe were distributed in liver and spleen,and the signs were reduced in accord with the increase of probe＇s doses in liver and spleen.The probe＇s metabolism was slow,and the probe was cleared from liver and spleen at 2weeks after the injection.The results of AAS and Prussian blue staining further testified the results of MRI.Conclusion Our data showed the biodistribution of SPIO-shRNA molecular probe in main organs can be traced by MRI in vivo. Meanwhile,it provides important information for the effectiveness of the probe by MRI at tumor in vivo.