关于<sup>131</sup>I标记酪氨酸修饰的血管靶向肽GX1用于消化道肿瘤诊治的实验研究-东南大学学报医学版

关于¹³¹I标记酪氨酸修饰的血管靶向肽GX1用于消化道肿瘤诊治的实验研究

单位：北京朝阳医院核医学科, 北京 100020

分类号：R735.2;R735.35

出版年·卷·期（页码）：2018·37·第二期（293-297）

摘要：

目的：设计合成酪氨酸（Tyr）修饰的肿瘤血管靶向肽（GX1），分析¹³¹I标记短肽Tyr-GX1在荷消化道肿瘤裸鼠体内的显影特征，探讨¹³¹I标记短肽Tyr-GX1作为肿瘤血管靶向诊治的可能性。方法：通过Iodogen碘标法对Tyr-GX1进行¹³¹I标记，检测标记率和稳定性；建立裸鼠模型并注射标记肽，分析胃癌组和结肠癌组24 h显像结果。结果：用直接标记法标记Tyr-GX1、GX1短肽，测定标记率提示无需纯化；本研究Tyr-GX1与肿瘤组织结合率较高。胃癌组Tyr-GX1组自8 h开始，肿瘤部位放射性浓聚灶高于心血池本底，随时间延长逐渐递增；结肠癌组Tyr-GX1组也自8 h开始出现放射性浓聚，随时间延长逐渐递增，到18 h达到高峰后略有下降，肿瘤部位和心血池本底放射性比值始终高于1；两种消化道肿瘤的浓聚及达到峰值时间各有特征；结肠癌组T/NT数值持续高于胃癌组。结论：本研究提示¹³¹I标记短肽Tyr-GX1具有良好的体内肿瘤血管靶向性，与肿瘤组织结合率较高，且两种消化道肿瘤的浓聚及达到峰值时间各有特征。¹³¹I标记短肽Tyr-GX1作为肿瘤血管靶向诊治具有一定价值和可能性。

Objective:To design a synthetic tumor tyrosine (Tyr)-modified tumor vascular targeting peptide (GX1) and to analyze the imaging characteristics of ¹³¹I-labeled short peptide Tyr-GX1 in nude mice bearing hepatocellular carcinoma. To investigate the effect of ¹³¹I-labeled short peptide Tyr-GX1 and the possibility of diagnosis and treatment of tumor blood vessels. Methods:Tyr-GX1 was labeled with iodogen iodine method to detect the labeling rate and stability. The nude mice models were established and the labeled peptide was injected to analyze the 24-hour imaging results of gastric cancer group and colon cancer group. Results:Tyr-GX1 and GX1 were detected by direct labeling method. The labeling rate was not purified. The binding rate of Tyr-GX1 and tumor tissue was higher in this study. In the gastric group, the Tyr-GX1 group started from the 8th hour, and the radioactive concentration of the tumor site was higher than that of the heart pool. The Tyr-GX1 group of the colon cancer group began to appear radioactive concentration in 8 hours. And the radioactivity ratio of the tumor site and the blood pool was always higher than 1. The concentration of the two kinds of digestive tract tumors and the peak time were all characterized. The T/NT value of the colon cancer group was higher than that in gastric cancer group. Conclusion:This study suggests that ¹³¹I labeled short peptide Tyr-GX1 has a good in vivo tumor vascular targeting, and tumor tissue binding rate is high. And the concentration of two kinds of digestive tract tumors and peak time have their own characteristics. ¹³¹I labeled short peptide Tyr-GX1 as a tumor blood vessels targeted diagnosis and treatment has a certain value and the possibility.

参考文献：

[1] 陈晓宇,黄陈,裘正军.早期胃癌的治疗现状与进展[J].现代生物医学进展,2015,15(12):2352-2354.
[2] 郭振英,曹伯良.血管内皮生长因子及相关促肿瘤血管生成分子及靶向治疗[J].中华病理学杂志,2010,39(4):282-285.
[3] ZHI J L,CHI H C.Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery[J].J Transl Med,2012,10(1):2386-2398.
[4] 潘中允.放射性核素治疗学[M].北京:人民卫生出版社,2006:298-304.
[5] AVRAM A M.Radioiodine scintigraphy with SPECT/CT:an important diagnostic tool for thyroid cancer staging and risk stratification[J].J Nucl Med Technol,2014,42(3):170-180.
[6] 李明,殷继鹏,惠晓丽,等.¹³¹I标记Tyr-GX1在荷瘤裸鼠体内分布和显像研究[J].现代生物医学进展,2013,13(9):1601-1604.
[7] WALKER J M.The protein protocols handbook[M].Totowa,NJ:Humana Press Inc,1996:673-674.
[8] 高文,张东生,刘璐.放射性核素在肿瘤内照射治疗领域的应用进展[J].东南大学学报:医学版,2004,23(5):344-346.
[9] 杨爱民,于燕,邓惠兴,等.99Tcm-HL91和18F-FDG显像与放疗关系的实验研究[J].国际放射医学核医学杂志,2011,35(4):217-219.
[10] 向敏,朱玲,刘馨,等.抗肿瘤血管生成靶向治疗进展[J].现代肿瘤医学,2014,22(9):2237-2240.
[11] 刘惊涛,惠晓丽,刘秦元,等.肿瘤血管内皮特异性靶向肽GX1与NGR在胃癌中显像差异分析[J].现代肿瘤医学,2014,22(4):729-732.
[12] 方如塘,惠晓丽,殷继鹏,等.新生血管特异性结合肽GX1抑制小鼠视网膜新生血管生成的实验研究[J].陕西医学杂志,2012,41(10):1275-1277.
[13] CHEN B,CAO S,ZHANG Y,et al.A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy[J].BMC Cell Biol,2009,9(10):63.
[14] De OLIVEIR É A,FAINTUCH B L,TARGINO R C,et al.Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models[J].Amino Acids,2016,48(3):821-831.
[15] 惠晓丽,刘惊涛,刘洋,等.肿瘤血管内皮特异性靶向肽GX1在结肠癌与肺癌中显像差异分析[J].现代肿瘤医学,2015,23(13):1783-1786.

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