| αvβ3靶向荧光剂术中近红外显影精准切除膀胱癌 |
| 投稿时间：2017-10-12 修订日期：2017-10-22 点此下载全文 |
| 引用本文：刘玉伟,孙闯.αvβ3靶向荧光剂术中近红外显影精准切除膀胱癌[J].医学研究杂志,2018,47(7):149-154 |
| DOI：
10.11969/j.issn.1673-548X.2018.07.035 |
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| 中文摘要: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。 |
| 中文关键词:近红外 影像引导治疗 吲哚花青绿 肿瘤靶向治疗 精氨酸-甘氨酸-天冬氨酸 |
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| Intraoperative Near-infrared Imaging for Precise Resection of Bladder Cancer by αvβ3 Targeting Fluorescent Agent |
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| Abstract: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. |
| keywords:Near-infrared Image-guided therapy ICG Tumor targeting RGD |
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