放疗后肿瘤99Tcm-MNLS乏氧显像变化与乏氧诱导因子-1α表达的相关性

doi:10.6040/j.issn.1671-7554.0.2016.413

摘要/Abstract

摘要： 目的探讨2-(2-甲基-5-硝基-1H-咪唑-1-基)磷酸乙酯(⁹⁹Tc^m-MNLS)乏氧显像监测肿瘤乏氧状态变化与肿瘤组织乏氧诱导因子-1α(HIF-1α)表达相关性。方法将荷瘤小鼠按显像时间分为放疗后显像组(R_12h、R_24h、R_36h)及对照组(C_12h、C_24h、C_36h)。放疗组肿瘤部位均给予单次15 Gy的照射剂量,对照组不予放疗。按照各组相应时间进行⁹⁹Tc^m-MNLS乏氧显像,并计算肿瘤部位与对侧正常组织放射性比值(T/NT),肿瘤组织进行HIF-1α免疫组化。将T/NT比值、HIF-1α免疫组化结果进行相关性分析。结果免疫组化结果显示,R_12h组T/NT比值、HIF-1α高于C_12h组,R_36h组低于C_36h组,(P均<0.000),R_24h组、C_24h组两组比较差异无统计学意义(P=0.612、0.731)。放疗组各组T/NT比值、HIF-1α表达呈正相关(r=0.793, P=0.003),对照组各组T/NT比值、HIF-1α表达也呈正相关(r=0.756, P=0.004)。结论 ⁹⁹Tc^m-MNLS乏氧显像T/NT比值与HIF-1α表达水平呈正相关, ⁹⁹Tc^m-MNLS乏氧显像可用于肿瘤放疗后疗效评估,并可为临床确定肿瘤分割照射时间提供依据。

关键词: 放射性核素显像, 乏氧诱导因子-1α, 动物模型, 乏氧

Abstract: Objective To explore the correlation between ⁹⁹Tc^m-MNLS hypoxic scintigraphy and hypoxia-inducible factor-1α(HIF-1α)expression in the hypoxic changes of tumors after radiotherapy. Methods The tumor-bearing mice were divided into radiotherapy groups(R_12h, R_24h, R_36h)and control groups(C_12h, C_24h, C_36h)according to the time of developing. The radiotherapy groups received an exposure dose of 15 Gy each time, while the control groups received no radiotherapy. After ⁹⁹Tc^m-MNLS hypoxic scintigraphy, the radioactivity ratio of tumor to non-tumor(T/NT)was calculated. The level of HIF-1α in tumors was evaluated. After that, the correlation between T/NT and HIF-1α level was analyzed. Results The T/NT and HIF-1α level in R_12h group and R_36h group were higher than those in the C_12h group and C_36h group(all P=0.000). There was no difference between the R_24h and C₂₄h groups(P=0.612, 0.731). The T/NT was positively correlated with HIF-1α level in the radiotherapy groups(r=0.793, P=0.003), as well as in the control groups(r=0.756, P=0.004). Conclusion Uptake of ⁹⁹Tc^m-MNLS and expression of HIF-1α are strongly 山东大学学报 (医学版)55卷8期 -胡玉敬,等.放疗后肿瘤⁹⁹Tc^m-MNLS乏氧显像变化与乏氧诱导因子-1α表达的相关性 \=-correlated to the changes of hypoxia in tumors after radiotherapy, and ⁹⁹Tc^m-MNLS hypoxic scintigraphy can provide the basis for the best time of reirradiation.

Key words: Hypoxia-inducible factor 1α, Radionuclide imaging, Hypoxia, Animal models

中图分类号:

R445.5

胡玉敬,吴大勇,张文艳,边艳珠,魏强,田丛娜,常胜利. 放疗后肿瘤⁹⁹Tc^m-MNLS乏氧显像变化与乏氧诱导因子-1α表达的相关性[J]. 山东大学学报（医学版）, 2017, 55(8): 30-34.

HU Yujing, WU Dayong, ZHANG Wenyan, BIAN Yanzhu, WEI Qiang, TIAN Congna, CHANG Shengli. Correlation between ⁹⁹Tc^m-MNLS hypoxic scintigraphy and hypoxia-inducible factor-1α after radiotherapy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 30-34.

参考文献

[1] 蒋力扬, 孟雪, 于金明. 用分子影像指导肿瘤精准治疗[J]. 中华核医学与分子影像杂志, 2016, 36(1): 3-6. JIANG Liyang, MENG Xue, YU Jinming. Precision therapy of oncology by molecular imaging [J]. Chin J Nucl Med Mol Imaging, 2016, 36(1): 3-6.
[2] 查智豪, 汪建军, 朱霖, 等. 新型乏氧肿瘤显像剂⁹⁹Tc^m-MNLS、⁹⁹Tc^m-MLS的合成及其在小鼠体内的生物分布[J]. 同位素, 2009, 22(4): 197-203. ZHA Zhihao, WANG Jianjun, ZHU Lin, et al. Preparation of hypoxic imaging agents ⁹⁹Tc^m-MNLS and ⁹⁹Tc^m-MLS and their biodistribution in mice[J]. Journal of Isotopes, 2009, 22(4): 197-203.
[3] Koumenis C, Alarcon R, Hammond E, et al. Regulation of p53 by hypoxia: dissociation of transcriptional repression and apoptosis from p53-dependent transactivation[J]. Mol Cell Biol, 2001, 21(4): 1297-1310.
[4] Blesius A, Cassier PA, Bertucci F, et al. Neoadiuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR 14 trial[J]. BMC Cancer, 2011, 11: 72. doi: 10.1186/1471-2407-11-72.
[5] 边艳珠, 胡玉敬, 吴大勇, 等. ⁹⁹Tc^m-MNLS乏氧显像评估肿瘤放疗后乏氧状态变化的实验研究[J].中华核医学与分子影像杂志, 2013, 33(5): 367-371. BIAN Yanzhu, HU Yujing, WU Dayon, et al. The assessment of tumor hypoxia variation after radiotherapy with ⁹⁹Tc^m-MNLS in mice tumor model[J]. Chin J Nucl Med Mol Imaging, 2013, 33(5): 367-371.
[6] 胡玉敬, 边艳珠, 吴大勇, 等. ⁹⁹Tc^m-MNLS与⁹⁹Tc^m-HL91乏氧显像评估肿瘤放疗后乏氧状态的对比实验研究[J]. 重庆医学, 2015, 44(19): 2618-2620. Hu Yujing, BIAN Yanzhu, ZHANG Wenyan, et al. Comparison between ⁹⁹Tc^m-MNLS and ⁹⁹Tc^m-HL91 in assessing the hypoxia of the tumor after radiotherapy[J]. Chongqing Yixue, 2015, 44(19): 2618-2620.
[7] Srinivasan A, Mohan S, Mukherji SK. Biologic imaging of head and neck cancer: the present and the future[J]. AJNR Am J Neuroradiol, 2012, 33(4): 586-594.
[8] Guan Y, Reddy KR, Zhu Q, et al. G-rich oligonucleotides inhibit HIF-1 alpha and HIF-2 alpha and block tumor growth[J]. Mol Ther, 2010, 18(1): 188- 197.
[9] Coothankandaswamy V, Liu Y, Mao SC, et al. The alternative medicine pawpaw and its acetogenin constituents suppress tumor angiogenesis via the HIF-1/VEGF pathway[J]. J Nat Prod, 2010, 73(5): 956- 961.
[10] Yang F, Zhang H, Mei Y, et al. Reciprocal regulation of HIF-1α and lincRNA-p21 modulates the Warburg effect[J]. Mol Cell, 2014, 53(1): 88-100.
[11] Reszec J, Rutkowski R, Chyczewski L. The expression of hypoxia-inducible factor-1 in primary brain tumors[J]. Int J Neurosci, 2013, 123(9): 657-662.
[12] Yorulmaz H, Ozkok E, Erguven M, et al. Effect of simvastatin on mitochondrial enzyme activities, ghrelin, hypoxia-inducible factor1 α in hepatic tissue during early phase of sepsis[J]. Int J Clin Exp Med, 2015, 8(3): 3640-3650.
[13] Generali D, Berruti A, Cappelletti MR, et al. Effect of primary letrozole treatment on tumor expression of mTOR and HIF-1α and relation to clinical response[J]. J Natl Cancer Inst Monogr, 2015, 2015(51): 64-66.
[14] Clarke RH, Moosa S, Anzivino M, et al. Sustained radiosensitization of hypoxic glioma cells after oxygen pretreatment in an animal model of glioblastoma and in vitro models of tumor hypoxia[J]. PLoS One, 2014, 9(10): e111199.
[15] Fan G, Bo J, Wan R, et al. The effect of lentiviral vector-mediated RNA interference targeting hypoxia-inducible factor 1α on the uptake of fluorodeoxyglucose((18)f)in the human pancreatic cancer cell line, patu8988[J]. Cancer Biother Radiopharm, 2015, 30(4): 160-168.
[16] Zornhagen KW, Hansen AE, Oxboel J, et al. Micro regional heterogeneity of 64Cu-ATSM and 18F-FDG uptake in canine soft tissue sarcomas: relation to cell proliferation, hypoxia and glycolysis[J]. PLoS One, 2015, 10(10): e0141379. doi: 10.1371/journal.pone.0141379. eCollection 2015.

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放疗后肿瘤⁹⁹Tc^m-MNLS乏氧显像变化与乏氧诱导因子-1α表达的相关性

Correlation between ⁹⁹Tc^m-MNLS hypoxic scintigraphy and hypoxia-inducible factor-1α after radiotherapy

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