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中华乳腺病杂志(电子版) ›› 2017, Vol. 11 ›› Issue (03) : 138 -143. doi: 10.3877/cma.j.issn.1674-0807.2017.03.003

论著

金属纳米探针BaGdF5-聚乙二醇作为CT 淋巴显像剂的实验研究
王秋虎1,2, 王涛1, 苏东玮3, 程超1, 左长京1,()   
  1. 1.200433 上海,第二军医大学长海医院核医学科
    2.221004 徐州医科大学医学影像学院
    3.200433 上海,第二军医大学长海医院甲乳外科
  • 收稿日期:2016-08-24 出版日期:2017-06-01
  • 通信作者: 左长京
  • 基金资助:
    国家自然科学基金资助项目(81471714)

Experimental study of metal nanoprobe BaGdF5-PEG as novel contrast agent in computed-tomography lymphography

Qiuhu Wang1,2, Tao Wang1, Dongwei Su3, Chao Cheng1, Changjing Zuo1,()   

  1. 1.Department of Nuclear Medicine
    2.Department of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, China
    3.Department of Thyroid and Breast Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
  • Received:2016-08-24 Published:2017-06-01
  • Corresponding author: Changjing Zuo
引用本文:

王秋虎, 王涛, 苏东玮, 程超, 左长京. 金属纳米探针BaGdF5-聚乙二醇作为CT 淋巴显像剂的实验研究[J/OL]. 中华乳腺病杂志(电子版), 2017, 11(03): 138-143.

Qiuhu Wang, Tao Wang, Dongwei Su, Chao Cheng, Changjing Zuo. Experimental study of metal nanoprobe BaGdF5-PEG as novel contrast agent in computed-tomography lymphography[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2017, 11(03): 138-143.

目的

探讨由聚乙二醇(PEG)修饰的金属纳米探针BaGdF5-PEG 作为CT 淋巴显像(CTLG)新型造影剂显像兔乳腺前哨淋巴结(SLN)的可行性。

方法

采用水热法制备金属纳米探针BaGdF5-PEG,并用巯基PEG(HS-PEG2000-NH2)作为稳定剂进行修正,通过透射电镜、X 射线能谱仪(EDX)等方法对纳米探针进行评估。 选取6 只健康雌性新西兰白兔,于每只兔右侧第2 乳晕皮下注射0.5 ml BaGdF5-PEG,并于注射前以及注射后的1、5、10、30、40、50、60、90 min 对兔行CT-LG,扫描范围为整个腋窝至第2 乳腺下方,通过所获图像识别SLN,记录SLN 在不同时间点时的CT 值,结果以±s 表示。 根据Suga 等的方法,如果SLN 的CT 峰值与平扫相比增加值超过30 HU,即可认为存在增强效应。完成CT-LG 后,以亚甲蓝为示踪剂对兔行乳腺前哨淋巴结活组织检查(SLNB),并将结果与CT-LG 结果对照。

结果

透射电镜图片显示制备的纳米颗粒BaGdF5 呈方形,平均粒径约20 nm;经修饰后的BaGdF5-PEG 的水合动力学直径为52 nm,所有元素(Ba、Gd、F)均在EDX 能谱上有显示。 以BaGdF5-PEG 作为CT-LG 造影剂,6 只实验兔各成功显影1 枚SLN,且CT-LG 结果与SLNB 结果一致。 SLN 的CT值在注射造影剂前为(12.8±5.07) HU,于造影剂注射后的10 min 达到峰值,为(47.4±9.1) HU,增加值>30 HU。

结论

金属纳米探针BaGdF5-PEG 可以作为CT-LG 造影剂,并能够实现对兔乳腺SLN 的长时间显像。

Objective

To study the feasibility of metal nanoprobe BaGdF5-PEG as the novel contrast agent in computed-tomography lymphography (CT-LG) used for detection of sentinel lymph nodes(SLNs) in rabbits.

Methods

The metal nanoprobe BaGdF5-PEG was synthesized by the hydrothermal method and further modified using HS-PEG2000-NH2 as stabilizing agents. BaGdF5-PEG was evaluated by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). Six healthy female New Zealand rabbits underwent CT-LG after subcutaneous injection of 0.5 ml BaGdF5-PEG in sub-areolar area of the right second breast. CT images were taken before and 1, 5, 10, 30, 40, 60, 90 min after contrast agent injection. The scanning ranged from the whole axilla to the area beneath the second breast. SLNs were recognized in CT-LG image. CT value of SLNs at different time points was recorded and expressed as ±s. According to Suga et al's method, if the peak CT value of SLNs was 30 HU higher than that of plain scanning, it was considered as enhancement effect. After CT-LG, sentinel lymph node biopsy (SLNB) was performed in rabbits, with methylene blue as tracer. The results of CT-LG were compared with the results of SLNB.

Results

The TEM image demonstrated that the prepared metal nanoparticles BaGdF5 was square in shape,with a mean diameter of 20 nm. The hydrated diameter of metal nanoprobe BaGdF5-PEG was 52 nm after modification. The involved elements (Ba, Gd and F) were all showed in EDX spectrum. CT-LG with BaGdF5-PEG as a contrast agent enabled the visualization of 6 SLNs (one in each rabbit), which was consistent with the results of SLNB. CT value of SLNs was (12.8±5.0) HU before injecting the contrast agent and reached a peak value of (47.4 ±9.1) HU 10 min after injecting the contrast agent, which was more than 30 HU higher than that of plain scanning.

Conclusion

The metal nanoprobe BaGdF5-PEG can be used as a contrast agent of CT-LG, which provides long-time visualization of SLNs in the breasts of rabbits.

图1 兔前哨淋巴结体表定位示意图 注:a 图所示,前哨淋巴结体表定位栅CT 显像;b 图所示,CT 图像定位前哨淋巴结后于体表相应的2 个栅格之间做直线,相交处为前哨淋巴结体表的位置
图2 纳米颗粒BaGdF5 的透射电镜观察图
图3 纳米颗粒BaGdF5 的X 射线能谱图
图4 兔乳腺前哨淋巴结CT 值与注射造影剂后时间变化的关系
图5 兔乳腺前哨淋巴结CT 淋巴显像 注:a 图所示,BaGdF5-PEG 皮下注射前,前哨淋巴结CT 值约为(12.8±5.0) HU;b 图所示,造影剂注射后10 min,前哨淋巴结CT 值约为(47.4±9.1) HU
图6 兔乳腺前哨淋巴结活组织检查 注:a 图所示,皮下注射亚甲蓝后在体表标记处作切口,可检出1 枚蓝染淋巴结(箭头);b 图所示,切取淋巴结后扩大切口,未发现其他蓝染淋巴结
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