人乳腺癌MCF-7裸鼠模型的99mTc-DTPA-CGRRAGGSC显像研究
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国家自然科学基金青年基金项目(81202032);江苏省"六大人才高峰"基金(2013-WSN-039);江苏省卫生计生委科研项目(Z201502);南京市科技计划项目(201303038)


99mTc-DTPA-CGRRAGGSC Scintigraphy in MCF-7 Breast Cancer Nude Mice Model
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    摘要:

    目的:探讨放射性核素99mTc标记环九肽CGRRAGGSC对荷人乳腺癌MCF-7裸鼠的显像研究。方法:环九肽CGRRAGGSC通过连接螯合剂DTPA与放射性核素99mTc螯合;纸层析法检测99mTc-DTPA-CGRRAGGSC的标记率和稳定性;免疫荧光检测DTPA-CGRRAGGSC和乳腺癌细胞MCF-7结合能力;经荷瘤鼠瘤体内分别注射剂量为1.85 MBq/0.05 mL的99mTc-DTPA-CGRRAGGSC-99mTcO-4和99mTcO-4+DTPA-CGRRAGGSC,分别于注药后0-0.5-1.0 -2.0-3.0-4.0 h进行SPECT静态显像。免疫组织化学评估IL-11Rα表达。结果:成功制备99mTc-DTPA-CGRRAGGSC,其标记率达到95%以上,在PBS和血清中37℃下放置12 h时放化纯仍有90%以上;DTPA-CGRRAGGSC和乳腺癌细胞MCF-7显著结合;经荷瘤鼠瘤体间质内注射99mTc-DTPA-CGRRAGGSC后4 h,肿瘤组织的放射性仍未消退,而瘤体间质内注射99mTcO-4和99mTcO-4+DTPA-CGRRAGGSC在0.5 h时肿瘤间质内放射性明显消退。乳腺癌组织IL-11Rα有较高的表达。结论:99mTc-DTPA-CGRRAGGSC对荷人乳腺癌MCF-7裸鼠具有靶向特异性,为进一步利用治疗性核素标记CGRRAGGSC对高表达IL-11Rα的乳腺癌的靶向治疗奠定基础。

    Abstract:

    Objective:To explore the scintigraphy of CGRRAGGSC labeled with 99mTc in nude mice bearing human breast cancer MCF-7. Methods: The CGRRAGGSC peptide was labeled with 99mTc using DTPA as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate and detect the stability. Immunofluorescence staining was used to evaluate the binding status of CGRRAGGSC peptide to human breast cancer cell. SPECT static scintigraphy at 0,0.5,1.0,2.0,3.0,4.0 h was performed in nude mice bearing human breast cancer after intratumoral injection of 1.85MBq/0.05 mL 99mTc-DTPA-CGRRAGGSC,99mTcO-4 and 99mTcO-4+DTPA-CGRRAGGSC,respectively. Immunohistochemistry assay was performed to observe the IL-11Rα protein levels in breast cancer. Results:99mTc-DTPA-CGRRAGGSC was radiolabeled successfully,the labeling rate was over 95% and the radiochemical purity in PBS and serum both were over 90% after 12 h at 37℃. Human breast cancer cells showed high binding abilities to CGRRAGGSC peptide. The scintigraphy showed that radioativity still deposited in tumor tissue at 4 h after intratumoral injection of 99mTc-DTPA-CGRRAGGSC,but radioactivity had faded obviously at 0.5 h after intratumoral injection of 99mTcO-4 or 99mTcO-4+DTPA-CGRRAGGSC. Breast cancer tissue had a higher expression of IL-11Rα. Conclusion:99mTc-DTPA-CGRRAGGSC can target the tumor tissue in nude mice bearing human breast cancer MCF-7,which lays a foundation for further study on the targeting therapeutic effect of therapeutic radionuclides rabeling CGRRAGGSC on breast cancer with expression of IL-11Rα.

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胡 瑶,李天女,孙 晋,丁德芹,刘 璐,王 强,徐玄飞,刘 圣,施海彬.人乳腺癌MCF-7裸鼠模型的99mTc-DTPA-CGRRAGGSC显像研究[J].南京医科大学学报(自然科学版),2017,(2):179-183

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  • 收稿日期:2016-06-17
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  • 在线发布日期: 2017-02-27
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