摘要
目的合成膀胱癌特异性探针用于近红外(near-infrared,NIR)引导下的膀胱肿瘤术中导航切除。方法将吲哚菁绿(indocyanine green,ICG)与精氨酸-甘氨酸-天冬氨酸(arginine-glycine-aspartic acid,RGD)通过化学偶合以制备膀胱癌特异性探针ICG-RGD。通过MTT法测定ICG-RGD的细胞毒性。体内、体外实验检测ICG-RGD的特异性。通过近红外(near-infrared,NIR)荧光成像指导手术切除病灶并检测残留肿瘤。结果在体内实验中,与NIR探针偶合的以整合素αvβ3为靶点的可快速清除的RGD肽可高度特异且敏感地检测膀胱癌、肿瘤残留量并限定肿瘤边界。膀胱癌特异性探针ICG-RGD具有良好的光学稳定性和生物兼容性,可被膀胱癌细胞特异性摄取。在肿瘤内滞留时间可达48h,最大肿瘤背景比为9.8。通过NIR成像下的术中导航技术可清晰显示肿瘤边缘并发现和切除<0.5mm的微小肿瘤灶。结论本研究所构建的肿瘤特异性探针ICG-RGD在动物模型中可有效地协助外科医生在NIR荧光成像引导下对膀胱肿瘤的精确切除。
Objective To synthesize a bladder cancer（BC）-specific probe for near-infrared（NIR） imaging-guided surgery. Methods Indocyanine green （ICG） was conjugated chemically with arginine-glycine-aspartic acid （RGD）. Toxicity of synthesized ICG-RGD was detected through MTT assay. Specificity of ICG-RGD was assessed in mice injected with MB49 BC cell line subcutaneously. Guided by NIR imaging, we surgically removed subcutaneous BC and detected tumor residuals. Results ICG-RGD was cleared fast in vivo. ICG-RGD detected BC and tumor residuals specifically and sensitively through targeting integrin αvβ3 in mouse model. ICG-RGD was optically stable, biocompatible and absorbed by BC cells specifically. The retention time of ICG-RGD in tumor was 48 h. The highest tumor-to-background ratio （TBR） was 9.8. Tumor margin was showed clearly by intra-operative NIR imaging through which minimal tumor lesions less than 0.5mm were detected and resected. Conclusion ICG-RGD, a BC-specific probe established by us, may assist surgical resection of BC precisely through NIR fluorescent imaging.
作者
刘玉伟
孙闯
Liu Yuwei;Sun Chuang(The Forth Affiliated Hospital of Harbin Medical University,Heilongjiang 150001,China)
出处
《医学研究杂志》
2018年第7期149-154,共6页
Journal of Medical Research
