近红外荧光分子探针Cy5-G3CNGRC靶向肿瘤血管生成显像的实验研究  

Experimental study of near infrared fluorescent molecular probe Cy5-G3CNGRC targeting tumor angiogenesis imaging

作　　者：王娇亚 刘松松 陶敏 熊玲 靖功伟 韩胜 任炳秀 WANG Jiaoya;LIU Songsong;TAO Min;XIONG Ling;JING Gongwei;HAN Sheng;REN Bingxiu(Department of Nuclear Medicine,the Third Affiliated Hospital of Zunyi Medical University(the First People's Hospital of Zunyi),Guizhou Zunyi563000,China)

机构地区：[1]遵义医科大学第三附属医院(遵义市第一人民医院)核医学科,贵州遵义563000

出　　处：《现代肿瘤医学》2023年第24期4519-4523,共5页Journal of Modern Oncology

基　　金：贵州省基础研究计划(自然科学类)项目(编号:黔科合基础[2019]1325号)。

摘　　要：目的:CD13受体是肿瘤血管生成过程的重要调节因子,而天冬酰胺酰-甘氨酸-精氨酸(NGR)氨基序列是CD13的特异性配体;我们制备了Cy5-GGGCNGRC(Cy5-G3CNGRC),以期为研究肿瘤血管生成提供一种新的影像方法。方法:以活化酯法制备Cy5-G3CNGRC经HPLC纯化后备用;分别以永生化人脐静脉内皮细胞(HUVEC)、人主动脉内皮细胞(HAEC)及CD13阳性表达的人纤维肉瘤细胞(HT-1080)和阴性表达的人直肠癌细胞(HT-29)建立体外细胞学模型以观察Cy5-G3CNGCR细胞学摄取情况;建立HT-29和HT-1080荷瘤小鼠模型通过腹腔注射Cy5-G3NGR(200μg/只)后0.5、1、2和4 h分别进行活体荧光成像,并计算肿瘤(靶,target,T)组织与肌肉(非靶,non-target,NT)组织的T/NT比值,然后对这些数据进行统计学分析。结果:细胞学实验结果提示,HUVEC、HAEC及HT-1080对Cy5-G3CNGRC摄取明显,而HT-29则几乎不摄取;HT-1080移植瘤最大T/NT比值明显高于HT-29移植瘤(2.25±0.49 vs 1.05±0.08,P=0.0047,n=5),且高峰值出现在注射后2 h左右。结论:Cy5-G3CNGRC在体内及体外均表现出了对CD13良好的亲和性,在肿瘤新生血管荧光成像方面有一定的应用价值。Objective:CD13 receptor is an important regulator of tumor angiogenesis,and the amino-sequence of asparaginyl-glycine-arginine(NGR)is a specific ligand of CD13.We prepared Cy5-GGGCNGRC(Cy5-G3CNGRC)in order to provide a new imaging method for studying tumor angiogenesis.Methods:Cy5-G3CNGRC was prepared by activated ester method and purified by HPLC.Immortalized human umbilical vein endothelial cells(HUVEC),human aortic endothelial cells(HAEC),CD13-positive human fibrosarcoma cells(HT-1080)and negative human rectal cancer cells(HT-29)were used to establish cell models in vitro to observe the uptake of Cy5-G3CNGCR.HT-29 and HT-1080 tumor-bearing mouse models were established by intraperitoneal injection of Cy5-G3NGR(200μg/mouse)and fluorescence imaging was performed at 0.5,1,2 and 4 h,respectively,then the T/NT ratio of tumor(target,T)tissue to muscle(non-target,NT)tissue was calculated,and these data were statisticallyanalyzed.Results:Cytological results indicated that HUVEC,HAEC and HT-1080 had obvious uptake of Cy5-G3CNGRC,while HT-29 had almost no uptake.The maximum T/NT ratio of HT-1080 grafts was significantly higher than that of HT-29 grafts(2.25±0.49 vs 1.05±0.08,P=0.0047,n=5),and the peak value occurred about 2 hours after injection.Conclusion:Cy5-G3CNGRC showed a good affinity to CD13 both in vivo and in vitro,which has certain application value in tumor neovascularization fluorescence imaging.

关 键 词：分子探针 荧光成像 天冬酰胺酰-甘氨酸-精氨酸(NGR) CD13 血管生成 

分 类 号：R73-3[医药卫生—肿瘤]