靶向超顺磁性脂质体整合素受体MR成像实验研究

曲海源;关丽明;陈春园;邓意辉;刘 屹;徐 克

中国临床医学影像杂志 ›› 2009, Vol. 20 ›› Issue (6) : 415-417.

中国临床医学影像杂志 ›› 2009, Vol. 20 ›› Issue (6) : 415-417.
论著

靶向超顺磁性脂质体整合素受体MR成像实验研究

  • 曲海源1,关丽明1,陈春园2,邓意辉3,刘 屹1,徐 克1
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Integrin receptor MR imaging with targeted superparamagnetic liposome

  • QU Hai-yuan1, GUAN Li-ming1, CHEN Chun-yuan2, DENG Yi-hui3, LIU Yi1, XU Ke1
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摘要

目的:合成靶向性超顺磁性长循环脂质体,进行肿瘤特异性磁共振成像。方法:将RGD短肽连接在包封SPIO的长循环脂质体表面,合成靶向性和非靶向长循环脂质体。与HUVEC细胞孵育流式细胞分析确定其受体亲和力;建立兔荷VX2肿瘤模型并进行磁共振靶向成像研究,观察其强化特征并与肿瘤标本的组织学检查相对照。结果:靶向超顺磁性脂质体对αvβ3整合素受体具有较高的特异性亲和力,与非靶向造影剂比较有显著统计学差异(P<0.002);该靶向造影剂能够在肿瘤内缓慢浓聚,给药后15h达最大值,此时对比噪声比(CNR)降至最低(P<0.01)。非靶向造影剂给药后2h即达最大浓聚,此时CNR最低(P<0.05)。两者强化机制不同。结论:RGD-超顺磁性长循环脂质体具有较高的弛豫率,能与αvβ3整合素受体特异性结合,在肿瘤特异性浓聚,并能够用MRI扫描进行证实。

Abstract

Objective: The ability of αvβ3 integrin targeted superparamagnetic liposomes to detect tumor angiogenesis was evaluated by in vitro fluorescence microscopy and in vivo MR molecular imaging. Methods: SPIO or calcein loaded liposomes were conjugated with or without Arg-Gly-Asp(RGD) peptides. Human umbilical vein endothelial cells(HUVECs) were incubated with calcein loaded targeted and non-targeted liposome or PBS and analyzed by flow cytometry and confocal laser scanning microscopy. VX2 tumor bearing rabbits were injected I.V with the two liposome preparations. MRI scanning was performed and the contrast to noise ratios(CNR) of the tumor pre- and post-contrast agent injection were compared. Results: Binding and uptake of RGD-liposomes by HUVECs was significantly increased when compared with non-targeted liposomes. After the contrast agent injection, the signal intensity and CNR of tumor drop to the bottom at 15 hour and 2 hour respectively for the targeted group and non-targeted group. Conclusion: The RGD targeted super-paramagnetic liposome we prepared got high relaxivities. It can bind specifically with αvβ3 integrins and be detected by in vivo MR imaging by 1.5T clinical MR machine.

关键词

整合素αvβ3 / 磁共振成像

Key words

Integrin alphaVbeta3 / Magnetic resonance imaging

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曲海源;关丽明;陈春园;邓意辉;刘 屹;徐 克. 靶向超顺磁性脂质体整合素受体MR成像实验研究[J]. 中国临床医学影像杂志. 2009, 20(6): 415-417
QU Hai-yuan;GUAN Li-ming;CHEN Chun-yuan;DENG Yi-hui;LIU Yi;XU Ke. Integrin receptor MR imaging with targeted superparamagnetic liposome[J]. Journal of China Clinic Medical Imaging. 2009, 20(6): 415-417
中图分类号: R73-3    R445.2   

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