[1]谭祖稳,吴梦雪,李运洁,等.99mTc-GE11分子探针在荷人肺腺癌裸鼠体内分布及受体显像研究[J].第三军医大学学报,2019,41(14):1350-1356.
 TAN Zuwen,WU Mengxue,LI Yunjie,et al.Biodistribution of 99mTc-GE11 molecular probe and receptor imaging in nude mice bearing lung adenocarcinoma[J].J Third Mil Med Univ,2019,41(14):1350-1356.
点击复制

99mTc-GE11分子探针在荷人肺腺癌裸鼠体内分布及受体显像研究
(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第14期
页码:
1350-1356
栏目:
基础医学
出版日期:
2019-07-30

文章信息/Info

Title:
Biodistribution of 99mTc-GE11 molecular probe and receptor imaging in nude mice bearing lung adenocarcinoma
作者:
谭祖稳吴梦雪李运洁雷成明邓婕段东
重庆医科大学附属第一医院核医学科
Author(s):

Department of Nuclear Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China 

关键词:
肺腺癌表皮生长因子受体多肽GE11核素分子探针
Keywords:
lung adenocarcinoma epidermal growth factor receptor polypeptide GE11 nuclide molecular probe
分类号:
R734.2;R817-33;R817.1
文献标志码:
A
摘要:

目的 制备靶向肺腺癌细胞跨膜表达蛋白表皮生长因子受体(epidermal growth factor receptor,EGFR)的核素分子探针99mTc-GE11,鉴定其理化性质并探讨其在荷瘤裸鼠体内分布及显像情况。方法 采用氯化亚锡氧化还原法对GE11进行99mTc标记,初步鉴定其标记率、比活度、放化纯度及稳定性等,并观察多肽标记物在荷瘤裸鼠体内的生物分布及显像情况。结果99mTc-GE11标记率为(93.12±0.83)%,比活度为(24.21±0.42)TBq/mmol。体外室温放置6、12 h后,其放化纯度仅下降了2.14%、3.11%。Sephadex G50柱层析后,其与血浆蛋白结合率为4.8%;与不同浓度半胱氨酸37 ℃温育1 h 后,未结合99mTc含量无明显变化;脂/水分配系数lgP为(-1.87 ±0.05);荷瘤裸鼠体内生物分布及SPECT显像示:99mTc-GE11在血液、肾脏中的放射性清除迅速,肿瘤组织可以选择性浓聚99mTc-GE11,在注射1.0 h时,肿瘤/肌肉比值达到最大,且肿瘤组织显影最清晰。结论 制备的99mTc-GE11小分子多肽探针理化特性理想,在荷人肺腺癌裸鼠模型中显像较好。

Abstract:
Objective To prepare a 99mTc-labled molecular probe (99mTc-GE11) targeting epidermal growth factor receptor (EGFR) on lung adenocarcinoma cells and evaluate its biodistribution and performance for EGFR imaging in nude mice bearing lung adenocarcinoma xenografts. Methods GE11 was labeled with 99mTc through oxidation and reduction of stannous chloride, and the labeling rate, specific activity, radiochemical purity and stability of 99mTc-GE11 were assessed. The biodistribution profile and receptor imaging performance of 99mTc-GE11 were evaluated in a nude mouse model bearing lung adenocarcinoma xenografts. ResultsThe mean labeling rate of 99mTC-GE11 was (93.12±1.43)%, and its mean specific activity was 24.21±0.42 TBq/mmol. At room temperature, the radiochemical purity of 99mTC-GE11 was reduced by 2.14% at 6 h and by 3.11% at 12 h. The results of chromatography with Sephadex-G50 column showed that the binding rate of 99mTC-GE11 with plasma proteins was 4.8%. At 37 ℃, incubation of 99mTc-GE11 with different concentrations of cysteine for 1 h did not cause significant changes in the level of free 99mTc. The fat/water distribution coefficient (lgP) of 99mTC-GE11 was -1.87±0.05. In the tumor-bearing nude mice, 99mTc-GE11 was rapidly cleared in blood and kidney after intravenous injection and was selectively accumulated in the tumor; the tumor/non-tumor (T/NT) ratio reached the highest level and the clearest tumor imaging was achieved at 1 h after the injection. Conclusion 99mTc-GE11 molecular probe prepared based on a small molecular polypeptide possesses good physiochemical properties with an optimal biodistribution profile, and allows clear in vivo tumor imaging in tumor-bearing nude mice.
 

参考文献/References:

[1]SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2016[J]. CA Cancer J Clin, 2017, 67(1): 7-30. DOI: 10.3322/caac.21332. 
[2]PASSIGLIA F, RIZZO S, DI MAIO M, et al. The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M mutation in NSCLC: A systematic review and meta-analysis[J]. Sci Rep, 2018, 8(1): 13379. DOI: 10.1038/s41598-018-30780-4. 
[3]XU L, HAUSMANN M, DIETMAIER W, et al. Expression of growth factor receptors and targeting of EGFR incholangiocarcinoma cell lines[J]. BMC Cancer, 2010, 10: 302. DOI: 10.1186/1471-2407-10-302. 
[4]WANG J S, WANG G B, LI B, et al. MiR-141-3p is a key negative regulator of the EGFR pathway in osteosarcoma[J]. Oncotargets Ther, 2018, 11: 4461-4478. DOI: 10.2147/OTT.S171304.
[5]SHEN J, ZHANG T, CHENG Z, et al.Lycorine inhibits glioblastoma multiforme growth through EGFR suppression[J]. J Exp Clin Cancer Res, 2018, 37(1): 157. DOI: 10.1186/s13046-018-0785-4. 
[6]MENG Q Q, LI Z. Molecular imaging probes for diagnosis and therapy evaluation of breast cancer[J]. Int J Biomed Imaging, 2013, 2013: 230487. DOI: 10.1155/2013/230487.
[7]LI Z H, ZHAO R J, WU X H, et al. Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery oftherapeutics[J]. FASEB J, 2005, 19(14): 1978-1985. DOI: 10.1096/fj.05-4058com. 
[8]郭妍, 李宗海, 顾健人, 等. 新多肽配体GE11与表皮生长因子受体的结合能力分析[J].分析测试学报, 2008, 27(12): 1318-1321. DOI:10.3969/j.issn.1004-4957. 2008.12.012.
GUO Y, LI Z H, GU J R.et al. Study on the binding ability of new peptide ligand GE11 and EGFR[J]. J Instrum Anal, 2008, 27(12): 1318-1321. DOI:10.3969/j.issn.1004- 4957.2008.12.012.
[9]查林, 冯世斌, 郑磊,等.整合素αvβ3放射性配体99Tcm-TP1326的制备及其正常兔显像研究[J]. 第三军医大学学报,2012, 34(3): 235-238. DOI:10.16016/j.1000-5404.2012.03.024.
CHA L, FENG S B, ZHENG L, et al. Preparation of 99Tcm-TP1326 targeting integrin αvβ3 receptor and its imaging in rabbits[J].J Third Mil Med Univ, 2012, 34(3): 235-238. DOI:10.16016/j.1000-5404.2012.03.024.
[10]丁小江,郑磊,黄定德,等.99Tcm标记VPAC1 配体TP1724 及其在动物体内分布与显像研究[J].第三军医大学学报,2016, 38(19): 2107-2113. DOI:10.16016 /j.1000-5404. 201603049
DING X J, ZHENG L, HUANG D D, et al. Distribution and imaging of a 99Tcm-labeled linear peptide derived from vasoactive intestinal peptide receptor in vivo[J]. J Third Mil Med Univ, 2016, 38(19): 2107-2113. DOI:10.16016 /j.1000-5404.201603049.
[11]邹丹丹,窦骏. 恶性肿瘤的分子靶点检测和靶向治疗[J]. 临床与实验病理学杂志, 2012, 28(9): 1026-1029. DOI: 10.13315/j.cnki.cjcep.2012.09.035
ZOU D D, DOU J. Molecular target detection and targeted therapy for malignant tumors [J]. Chin J Clin Exp Pathol,2012, 28(9): 1026-1029. DOI: 10.13315/j.cnki.cjcep.2012.09.035.
[12]XU N Q, FANG W F, MU L B, et al. Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer[J]. Oncotarget, 2016, 7(4): 3884-3896. DOI: 10.18632/oncotarget.6461. 
[13]LEE M. Is EGFR expression important in non-small cell lung cancer?[J]. Thorax, 2006, 61(2): 98-99. DOI: 10.1136/thx. 2005.047936. 
[14]CONSTANTINOU C, PAPADOPOULOS S, KARYDA E, et al. Expression and clinical significance of claudin-7, PDL-1, PTEN, c-kit, c-met, c-myc, ALK, CK5/6, CK17, p53, EGFR, ki67, p63 in triple-negative breast cancer-A single centre prospective observational study[J]. In Vivo, 2018, 32(2): 303-311. DOI: 10.21873/invivo.11238. 
[15]LOUD J T, PETERS J A, FRASER M, et al. Applications of advances in molecular biology and genomics to clinical cancer care[J].Cancer Nurs, 2002, 25(2): 110-122. 
[16]HOPKINSA L, GROOM C R. The druggable genome[J]. Nat Rev Drug Discov, 2002, 1(9): 727-730. DOI: 10.1038/nrd892. 
[17]GOLDENBERG D M. Advancing role of radiolabeled antibodies in the therapy of cancer[J]. Cancer Immunol, Immunother, 2003, 52(5): 281-296.
[18]TARHINI A A, KIRKWOOD J M. Clinical and immunologic basis of interferon therapy in melanoma[J]. Ann N Y Acad Sci, 2009, 1182: 47-57. DOI: 10.1111/j.1749-6632. 2009.05073.x. 
[19]李宗海.表皮生长因子受体介导的靶向性基因治疗导入系统[D].上海:复旦大学,2005. 
LI Z H. Epidermal growth factor receptor-targeted gene delivery system[D]. Shanghai: Fudan University, 2005.
[20]李贵平,黄宝丹,杜丽,等.99mTc标记的新型肺癌多肽分子探针及其生物学分布[J].南方医科大学学报,2013, 33(8): 1169-1172.DOI:10.3969/j.issn.1673-4254.2013.08.15.
LI G P, HUANG B D, DU L, et al.99mTc radiolabeling of a novel polypeptide molecular probe for lung cancer and its biodistribution in animals[J].J South Med Univ, 2013, 33(8): 1169-1172. DOI:10.3969/j.issn.1673-4254.2013.08.15.
 

相似文献/References:

[1]刁鑫伟,叶明福,谢启超,等.二氢睾酮对前列腺癌LNcap和PC-3细胞株EGFR mRNA表达的影响[J].第三军医大学学报,2005,27(16):1690.
[2]王孟昭,张紫萱.肺癌的靶向治疗[J].第三军医大学学报,2012,34(20):2035.
 Wang Mengzhao,Zhang Zixuan.Target therapy in lung cancer[J].J Third Mil Med Univ,2012,34(14):2035.
[3]杨庆羚,刘翩,王斌,等.EGFR-TKIs治疗晚期非小细胞肺癌并发间质性肺炎4例报告并文献复习[J].第三军医大学学报,2012,34(20):2060.
 Yang Qingling,Liu Pian,Wang Bin,et al.Interstitial pneumonia in EGFR-TKIs-treated non-small-cell lung cancer: report of 4 cases and review of the literature[J].J Third Mil Med Univ,2012,34(14):2060.
[4]刘瑞青,申淑景,马杰,等.肺腺癌组织中TTF-1和SPA的表达对EGFR突变的临床预测价值[J].第三军医大学学报,2012,34(22):2314.
 Liu Ruiqing,Shen Shujing,Ma Jie,et al.Clinical value of TTF-1 and SPA expression in predicting EGFR mutations in lung adenocarcinoma[J].J Third Mil Med Univ,2012,34(14):2314.
[5]白莉,祝蓉,陈智鸿,等.靶向EGFR基因的siRNA表达载体构建及其生物学效应的研究[J].第三军医大学学报,2005,27(23):2307.
[6]刁鑫伟,叶明福,张哉根,等.前列腺癌AR表达与细胞增殖的关系[J].第三军医大学学报,2005,27(17):1799.
[7]郭启帅,黄曦,吴永忠,等.靶向EGFR基因RNA干扰对人卵巢癌SKOV3细胞增殖的抑制作用[J].第三军医大学学报,2009,31(23):2338.
 GUO Qi-shuai,HUANG Xi,WU Yong-zhong,et al.RNA interference targeting EGFR on proliferation of human ovarian carcinoma cell line SKOV3[J].J Third Mil Med Univ,2009,31(14):2338.
[8]薛晓倩,黄学宽,高宁,等.自制方化湿液对湿阻证大鼠胃黏膜的保护作用及对表皮生长因子受体表达的影响[J].第三军医大学学报,2011,33(18):1928.
 Xue Xiaoqian,Huang Xuekuan,Gao Ning,et al.Protective effect of dampness-releasing liquid on gastric mucosa and expression of epithelial growth factor receptor in rats with dampness retention syndrome[J].J Third Mil Med Univ,2011,33(14):1928.
[9]吴砚樵,周向东.慢性机械压力诱导气道上皮黏蛋白5AC的表达[J].第三军医大学学报,2010,32(15):1594.
 Wu Yanqiao,Zhou Xiangdong.Chronic mechanical stress induces mucin 5AC protein expression in rat airway epithelial cells in vitro[J].J Third Mil Med Univ,2010,32(14):1594.
[10]段东,李少林,朱玉泉,等.99Tcm-EGFR-McAb及99Tcm-CD44-McAb单独及联合用于荷人肺腺癌裸鼠的显像研究[J].第三军医大学学报,2009,31(13):1287.
 DUAN Dong,LI Shao-lin,ZHU Yu-quan,et al.Effects of radioimmunoimaging with 99Tcm-EGFR-McAb or 99Tcm-CD44-McAb or combined application of both on nude mice bearing human lung adenocarcinoma[J].J Third Mil Med Univ,2009,31(14):1287.

更新日期/Last Update: 2019-07-22