利用乏氧显像评估针对乳腺癌血管的治疗

doi:10.11904/j.issn.1002-3070.2023.01.008

实用肿瘤学杂志 ›› 2023, Vol. 37 ›› Issue (1): 46-51.doi: 10.11904/j.issn.1002-3070.2023.01.008

利用乏氧显像评估针对乳腺癌血管的治疗

朱静¹, 孟昕², 付鹏², 许鹏², 高慧棋²

1.哈尔滨医科大学附属第一医院老年病房(哈尔滨 150001);
2.哈尔滨医科大学附属第一医院核医学科

收稿日期:2022-07-01 修回日期:2022-12-08 出版日期:2023-02-28 发布日期:2023-03-21
通讯作者: 高慧棋,E-mail:ghq790601@163.com
作者简介:朱静,女,(1978-),硕士,主治医师,从事肿瘤的多学科联合治疗的研究。
基金资助:
黑龙江省自然科学基金资助项目(编号:LH2019H083)

Application of hypoxia imaging to assess vascular therapies for breast cancer

ZHU Jing¹, MENG Xin², FU Peng², XU Peng², GAO Huiqi²

1. Department of Geriatric Disease,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;
2. Department of Nuclear Medicine,The First Affiliated Hospital of Harbin Medical University

Received:2022-07-01 Revised:2022-12-08 Online:2023-02-28 Published:2023-03-21

摘要/Abstract

摘要： 目的应用内皮抑素基因和³²P-磷酸铬胶体内照射治疗大鼠乳腺癌种植瘤,并利用乏氧显像剂^99mTc-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(^99mTc-HL91)评估治疗后肿瘤乏氧状况的变化。方法 80只雄性Wistar大鼠皮下注射Walker-256乳腺癌细胞,通过瘤内注射的方式给药,建立种植瘤模型并随机分为四组:对照组(0.9%生理盐水)、³²P组(³²P-磷酸铬胶体)、endo组(含endostatin基因的质粒)和³²P+endo组(³²P-磷酸铬胶体和含endostatin基因的质粒的混合物),治疗起始和治疗后7天,进行^99mTc-HL91乏氧显像,计算各组大鼠肿瘤部位与对侧正常组织放射性计数比值(T/NT)。每4天测量肿瘤大小,计算肿瘤生长率,治疗20天后取肿瘤组织染色,计算各组大鼠肿瘤微血管密度(MVD)、凋亡指数(AI)、血管内皮生长因子(VEGF)的阳性率。结果 ³²P组和endo组肿瘤生长率低于对照组,³²P+endo组最低(P＜0.001)。³²P组MVD、VEGF高于对照组(P＜0.05),endo组和³²P+endo组低于对照组(P＜0.05)。³²P组和endo组AI高于对照组,³²P+endo组最高(P＜0.001)。endo组和³²P+endo组T/NT比值高于对照组和³²P组(P＜0.05)。结论肿瘤经不同治疗方法后乏氧的改变各不相同,^99mTc-HL91能在体内监测肿瘤的乏氧状况,从而早期评估肿瘤血管抑制剂的治疗效果。

关键词: 乏氧, HL91, 内皮抑素基因, 32磷

Abstract: Objective The Objective of this study was to use endostatin gene and ³²P-chromic phosphate colloid to treat implanted tumor of breast cancer in rats,and the hypoxic imaging agent ^99mTc-4,9-diazepine-3,3,10,10-tetramethyldodecane-2,11-diketoxime(^99mTc-HL91)was used to evaluate the changes of tumor hypoxia after treatment. Methods Eighty male Wistar rats were subcutaneously injected with walker-256 breast cancer cell to establish implanted tumor models and randomly divided into 4 groups,which were administered by intratumoral injection:the control group(0.9% normal saline),³²P group(³²P-chromium phosphate colloid),endostatin(endo)group(plasmid containing endostatin gene)and ³²P+endo group(mixture of ³²P-chromium phosphate colloid and plasmid containing endostatin gene).^99mTc-HL91 hypoxia imaging was performed at the beginning of treatment and 7 days after treatment,and the ratio of radioactive count(T/NT)between the tumor site and contralateral normal tissue of rats in each group was calculated.The tumor size was measured every 4 days,and the tumor growth rate was calculated.After 20 days of treatment,the tumor tissues were stained,and the positive rates of tumor microvessel density(MVD),apoptosis index(AI)and vascular endothelial growth factor(VEGF)in rats in each group were calculated. Results The tumor growth rate in the ³²P group and endo group was lower than that in the control group,and the tumor growth rate in the ³²P+endo group was the lowest(P＜0.001).MVD and VEGF in the ³²P group were higher than those in the control group(P＜0.05),and those in the endo group and ³²P+endo group were lower than those in the control group(P＜0.05).The AI in the ³²P group and endo group was higher than that in the control group,and the AI in the ³²P+endo group was the highest(P＜0.001).The ratio of T/NT in the endo group and ³²P+endo group was higher than that in the control group and ³²P group(P＜0.05). Conclusion The changes of hypoxia in tumors after different treatment methods are different.^99mTc-HL91 can monitor the hypoxic status of tumors in vivo,so as to evaluate the therapeutic effect of tumor blood vessel inhibitors in the early stage.

Key words: Hypoxia, HL91, Endostatin gene, ³²P

中图分类号:

R730.58

朱静, 孟昕, 付鹏, 许鹏, 高慧棋. 利用乏氧显像评估针对乳腺癌血管的治疗[J]. 实用肿瘤学杂志, 2023, 37(1): 46-51.

ZHU Jing, MENG Xin, FU Peng, XU Peng, GAO Huiqi. Application of hypoxia imaging to assess vascular therapies for breast cancer[J]. Journal of Practical Oncology, 2023, 37(1): 46-51.

参考文献

1 Li Y,Zhao L,Li XF.Hypoxia and the tumor microenvironment[J].Technol Cancer Res Treat,2021,20(6):437-447.
2 Tinganelli W,Durante M.Tumor hypoxia and circulating tumor cells[J].Int J Mol Sci,2020,21(24):9592.
3 Huang Y,Fan J,Li Y,et al.Imaging of tumor hypoxia with radionuclide-labeled tracers for PET[J].Front Oncol,2021,11:731503.
4 Graham K,Unger E.Overcoming tumor hypoxia as a barrier to radiotherapy,chemotherapy and immunotherapy in cancer treatment[J].Int J Nanomedicine,2018,13:6049-6058.
5 Bhardwaj B,Revannasiddaiah S,Bhardwaj H,et al.Molecular targeted therapy to improve radiotherapeutic outcomes for non-small cell lung carcinoma[J].Ann Transl Med,2016,4(3):50.
6 Chen X,Nie J,Dai L,et al.Comparison of endostatin combined with PT-DC versus bevacizumab combined with PT-DC in the first-line treatment of advanced lung adenocarcinoma:a retrospective propensity score-matched cohort study[J].Ann Palliat Med,2021,10(7):7847-7856.
7 Li L,Li Y,Zou H.A novel role for apatinib in enhancing radiosensitivity in non-small cell lung cancer cells by suppressing the AKT and ERK pathways[J].PeerJ,2021,9:e12356.
8 Feng L,Wang Z,Jing L,et al.Recombinant human endostatin combined with chemotherapy for advanced squamous cell lung cancer:a meta-analysis[J].World J Surg Oncol,2021,19(1):64.
9 Xu X,Li R,Zhu P,et al.Clinical efficacy and safety of maintenance therapy for advanced non-small cell lung cancer:a retrospective real-world study[J].World J Surg Oncol,2021,19(1):231.
10 An J,Lv W.Endostar(rh‐endostatin)versus placebo in combination with vinorelbine plus cisplatin chemotherapy regimen in treatment of advanced non‐small cell lung cancer:a meta‐analysis[J].Thoracic Cancer,2018,9(5):606-612.
11 Zhu J,Chen G,Niu K,et al.Efficacy and safety of recombinant human endostatin during peri-radiotherapy period in advanced non-small-cell lung cancer[J].Future Oncol,2022,18(9):1077-1087.
12 Abrantes AM,Serra ME,Goncalves AC,et al.Hypoxia-induced redox alterations and their correlation with ^99mTc-MIBI and ^99mTc-HL-91 uptake in colon cancer cells[J].Nucl Med Biol,2010,37(2):125-132.
13 Wen G,Huang XB,Zhang WD,et al.Primary exploration of individual biological boosting target volume for locally advanced nasopharyngeal carcinoma[J].Zhonghua Yi Xue Za Zhi,2012,92(45):3207-3210.
14 Chen Z,Guo W,Wu Q,et al.Tumor reoxygenation for enhanced combination of radiation therapy and microwave thermal therapy using oxygen generation in situ by CuO nanosuperparticles under microwave irradiation[J].Theranostics,2020,10(10):4659-4675.
15 Wu J,Zhao X,Sun Q,et al.Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model[J].Biomed Pharmacother,2020,125:109746.
16 Wang N,Gao Q,Tang J,et al.Anti-tumor effect of local injectable hydrogel-loaded endostatin alone and in combination with radiotherapy for lung cancer[J].Drug Delivery,2021,28(1):183-194.
17 Marques F,Poli E,Rino J,et al.Low doses of ionizing radiation enhance the angiogenic potential of adipocyte conditioned medium[J].Radiat Res,2019,192(5):517-526.

[1]	陈荣梅综述,葛晓峰审校. 鼻咽癌组织中HIF-1α、GLUT-1的表达与放疗敏感性关系的研究进展[J]. 实用肿瘤学杂志, 2013, 27(5): 452-456.
[2]	李世杰综述, 刘瑞宝审校. β-catenin在肝细胞癌及乏氧微环境中的研究进展[J]. 实用肿瘤学杂志, 2013, 27(4): 372-376.
[3]	罗顺祥,戈伟,刘梓良,李伟,宋锐,刘梁,郑永法. 恩度联合放疗对移植瘤HIF-1α及GLUT-1表达的影响[J]. 实用肿瘤学杂志, 2013, 27(3): 242-245.
[4]	刘梁, 戈伟, 明平坡, 张金忠, 张令, 王慧敏, 曹德东, 郑永法. 恩度联合放射治疗对Lewis肺癌小鼠生长以及碳酸酐酶Ⅸ和乏氧诱导因子表达的影响[J]. 实用肿瘤学杂志, 2012, 26(5): 385-388.
[5]	焦明秀综述, 崔亚利审校. 肿瘤乏氧显像在预测甲状腺癌内放疗疗效的临床应用[J]. 实用肿瘤学杂志, 2009, 23(6): 593-596.

利用乏氧显像评估针对乳腺癌血管的治疗

Application of hypoxia imaging to assess vascular therapies for breast cancer

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价