SPIO-shRNA双功能分子探针药动学及活体MR成像研究

发布时间：2018-03-28 16:32

本文选题：药代动力学　切入点：分子探针　出处：《药学学报》2015年10期

【摘要】：本研究探讨SPIO-sh RNA双功能分子探针在活体内的药代动力学特征及磁共振(magnetic resonance,MR)成像无创评估其主要脏器分布。将18只新西兰大白兔随机分为3组,分别注射不同剂量的分子探针,于注射前30 min及注射后不同时间点采血,测量铁含量以分析探针药代动力学。24只昆明(KM)小鼠随机分为4组,以每只小鼠尾静脉注射200μL生理盐水为对照组,另3组分别注射不同剂量的分子探针,于注射后24 h行MRI扫描,扫描结束后立即取肝、脾、肾、脑及肌肉,制作切片行普鲁士蓝染色,观察探针在体内主要脏器组织的分布情况。结果显示,本探针的药代动力学符合二室模型,半衰期超过3 h;MRI显示探针在正常小鼠体内主要分布于肝脏与脾脏,肝脾MRI信号随着探针剂量的增加而降低(均P0.05),组织切片普鲁士蓝染色证实了MRI检查结果,同时显示探针绝大部分能够逃避单核吞噬细胞系统的吞噬。本研究明确了SPIO-sh RNA分子探针在动物体内的药代动力学及主要脏器分布,为进一步的肿瘤活体成像时间及剂量的选择提供了重要参考价值。
[Abstract]:This study was to investigate the pharmacokinetic characteristics and magnetic resonance SPIO-sh RNA dual functional molecular probe in vivo (magnetic resonance MR) imaging is a non-invasive assessment of the main organ distribution. 18 New Zealand white rabbits were randomly divided into 3 groups, were injected with various doses of molecular probe before injection and after injection of 30 min at the time of blood sampling, measurement of iron content analysis to probe the pharmacokinetics of.24 in Kunming (KM) mice were randomly divided into 4 groups, with each mouse tail vein injection of 200 L normal saline as the control group, the other 3 groups were injected with different doses of molecular probes, after injection of 24 h underwent MRI scanning, liver immediately after the scan, spleen, kidney, brain and muscle, making sections were stained with Prussian blue staining, observe the distribution of probe in main organs in vivo. The results showed that the probe fitted to the two compartment model of pharmacokinetics, the half-life of over 3 h; MRI probe In normal mice and in liver and spleen, liver and spleen MRI signal decreased with increasing probe dose (P0.05), histological Prussian blue staining confirmed the findings of MRI, while most of probes can escape the phagocytosis of mononuclear phagocyte system. The paper defines the SPIO-sh RNA molecular probe in pharmacokinetics and the main organs of animal distribution, tumor in vivo imaging time and dose further selection provides an important reference value.

【作者单位】：重庆医科大学附属第一医院放射科;
【基金】：国家自然科学基金资助项目(81171366) 国家临床重点专科建设项目[(2013)544]
【分类号】：R969.1;R445.2

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