摘要
目的建立靶向性超顺磁性长循环脂质体靶向探针,进行兔Vx2肿瘤磁共振靶向成像,评价小动物磁共振扫描序列及方法。方法将精氨酸-甘氨酸-天冬氨酸(RGD)短肽通过硫醚键连接在包封超顺磁性氧化铁(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。流式细胞分析确定其受体亲和力。建立兔皮下荷Vx2肿瘤模型并进行磁共振靶向成像研究。对比不同磁共振扫描方法的区别及影响图像质量的相关因素。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(P<0.01)。该靶向造影剂能够在肿瘤内缓慢浓聚,给药后15h达最大值。非靶向造影剂给药后2h即达最大浓聚。磁敏感加权(SWI)扫描序列图像质量较好。动物摆位、给药剂量及匀场对图像质量影响较大。结论RGD-超顺磁性长循环脂质体能在肿瘤内特异性浓聚,并能够用SWI序列MRI扫描进行证实。
Objective To evaluate the thechniques for MR molecular imaging of angiogenesis in rabbit Vx2 tumor with αvβ3 integrins targeted superparanlagnetic liposomes, and to compare the different MR sequences. Methods SPIO or calcein loaded liposomes were conjugated with or without Arg-Gly-Asp （RGD）peptides. Human umbilical vein endothelial cells （HUVECs） incubated with calcein loaded targeted and non-targeted liposomes or PBS were analyzed by flow cytometry. In the competitive experiment, HUVECs were incubated with tenfold concentration free RGD,then RGD fluorescent liposomes were added. Vx2 tumor-bearing rabbits were injected LV with the two liposome preparations on concentration of 3 mg Fe/kg body weight. Before and after injection, MRI scanning was performed for several times. SWI and T2＊ scan sequences were used respectively. The Contrast-to-noise Ratios （CNR） of the tumor pre-and pest-contrast agent injection were compared. The rabbits were then sacrificed and the tumor were excised and used for histological analysis. The MR techniques of rabbit scaning were also evaluated. Results Binding and uptake of RGD-liposomes by HUVECs were significantly increased when compared with non-targeted hposoraes. The CNR of tumor draped to the bottom at the fifteenth hour and the second hour respectively for the targeted group and non-targeted group. SWI sequences are better than T2＊. Conclusion The RGD targeted super-paramagnetic liposomes can bind specifically with αvβ3 integrins and be detected in vivo by MR imaging by 1.5T clinical MR machine.
出处
《中国医科大学学报》
CAS
CSCD
北大核心
2009年第3期163-166,共4页
Journal of China Medical University
基金
国家自然科学基金资助项目(30500139)
