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肿瘤靶向荧光新材料Cy-Biotin的排泄特性及其在乳腺癌术中导航的应用探索

Excretion characteristics of the tumor-targeted fluorescent new material Cy-Biotin and its application exploration in intraoperative navigation for breast cancer

摘要目的:探索肿瘤靶向荧光新材料Cy-Biotin的排泄特性及术中导航的成像性能。方法:首先向BALB/c nude小鼠尾静脉注射定量的肿瘤靶向荧光新材料,在既定时间点采集、量化小鼠仰卧姿势的全身荧光图像,观察小鼠的肝脏、肾脏及膀胱排泄器官的荧光信号,绘制时间-荧光强度谱图,评价荧光新材料的排泄路径与排泄动力学。进一步在新鲜的人乳腺肿瘤离体样本上探索新材料的术中导航成像性能,通过瘤内注射新材料Cy-Biotin,在荧光信号指引下,分别采集高亮度组织与低亮度组织,通过病理分析确认高亮度组织是否为肿瘤组织,低亮度组织是否为瘤旁的正常乳腺组织,获得肿瘤切缘检出性能,评价新材料判定肿瘤切缘准确性。结果:尾静脉注射肿瘤靶向荧光新材料后,在2~28 h内,荧光信号主要集中于膀胱与肾脏,在给药24 h后,小鼠全身已无明显荧光信号,说明新材料已从小鼠体内基本排泄完全,说明新材料主要通过肾脏、肝脏排泄,且体内排泄较快,预计安全性较好;新材料可在数秒内特异性点亮人离体乳腺癌组织,术中病理分析表明高亮度组织均为肿瘤组织,低亮度组织均为瘤旁正常乳腺组织,即切缘精度与病理切片分析匹配度为100%。结论:肿瘤靶向荧光新材料Cy-Biotin主要通过肾脏和肝脏快速排泄出体内,预计安全性较好,可精准显影人离体乳腺肿瘤切缘,具有较好临床应用前景。

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abstractsObjective:To explore the excretion characteristics of the tumor-targeted fluorescent new material Cy-Biotin and its imaging performance in intraoperative navigation.Methods:Quantitative injections of the tumor-targeted fluorescent new material were first administered via the tail vein of BALB/c nude mice. At predefined time points, whole-body fluorescence images were collected and quantified while the mice were in the supine position. The fluorescence signals from the liver, kidneys, and bladder (the primary excretory organs) were observed. A time-fluorescence intensity spectrum was constructed to evaluate the excretion pathway and kinetics of the fluorescent material. Further, the intraoperative navigation imaging performance of the new material was explored using fresh human breast cancer tissue samples. The material Cy-Biotin was injected into the tumor, and under fluorescent signal guidance, tissues with high and low brightness were separately collected. Pathological analysis confirmed whether the high-brightness tissue was tumor tissue and whether the low-brightness tissue was normal adjacent breast tissue. Tumor margin detection performance was evaluated, and the accuracy of tumor margin determination using the new material was assessed.Results:After intravenous injection of the tumor-targeted fluorescent material, fluorescence signals were predominantly concentrated in the bladder and kidneys within 2-28 hours. After 24 hours post-administration, no significant fluorescence signals were observed throughout the mouse's body, indicating that the material was almost completely excreted from the mouse body. This suggests that the material is primarily excreted through the kidneys and liver, with relatively fast excretion kinetics, indicating good safety. The new material could specifically highlight human ex vivo breast cancer tissue within seconds. Intraoperative pathological analysis showed that high-brightness tissues were all tumor tissues, and low-brightness tissues were all normal adjacent breast tissues. The accuracy of tumor margin detection matched 100% with pathological analysis.Conclusions:The tumor-targeted fluorescent new material Cy-Biotin is primarily excreted rapidly through the kidneys and liver, indicating good safety. It can accurately highlight tumor margins in human ex vivo breast cancer tissue, suggesting a promising clinical application.

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