[1]刘晓梅,魏玲格,张芳.以血管生成为分子靶点的放射性核素显像分子探针在肿瘤个体化用药中的应用[J].国际放射医学核医学杂志,2017,41(5):363-369.[doi:10.3760/cma.j.issn.1673-4114.2017.05.011]
 Liu Xiaomei,Wei Lingge,Zhang Fang.Targeting angiogenesis of radionuclide imaging molecular probes for tumor individualized medicine[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(5):363-369.[doi:10.3760/cma.j.issn.1673-4114.2017.05.011]
点击复制

以血管生成为分子靶点的放射性核素显像分子探针在肿瘤个体化用药中的应用(/HTML)
分享到:

《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
41
期数:
2017年第5期
页码:
363-369
栏目:
综述
出版日期:
2017-09-25

文章信息/Info

Title:
Targeting angiogenesis of radionuclide imaging molecular probes for tumor individualized medicine
作者:
刘晓梅 魏玲格 张芳
050051 石家庄, 河北医科大学第三医院核医学科
Author(s):
Liu Xiaomei Wei Lingge Zhang Fang
Department of Nuclear Medicine, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
关键词:
血管内皮生长因子类整合素αvβ3血管生成放射性核素显像分子探针个性化用药
Keywords:
Vascular endothelial growth factorIntegrin αvβ3AngiogenesisRadionuclide imagingMolecular probesIndividualized medicine
DOI:
10.3760/cma.j.issn.1673-4114.2017.05.011
摘要:
血管生成对肿瘤生长至关重要,以肿瘤血管为靶点的抗血管生成治疗日益受到重视,但抗血管生成疗法的机制以及治疗后产生的耐药性尚不明确。无创性放射性核素分子显像可阐明基本的药物机制以及耐药通路,并通过治疗前和治疗期间的靶点量化表达实现个体化的抗血管生成治疗。笔者重点讨论在血管生成过程中4个关键蛋白质,即血管内皮生长因子(VEGF)及其受体、整合素αvβ3、细胞外基质纤连蛋白、基质金属蛋白酶(MMP)的表达在放射性核素标记分子显像探针发展中的作用及其在个体化抗血管生成疗法中的应用。
Abstract:
Angiogenesis is essential for tumor growth, and anti-angiogenesis therapy has gained increasing attention in clinical oncology. Nonetheless, the mechanisms underlying anti-angiogenic therapeutics and cancer cell resistance to these drugs remain unclear. Non-invasive nuclide molecular imaging can be used to determine the mechanism of basic drugs and drug-resistant pathways. This tool can also be utilized to personalize anti-angiogenic therapy by enabling target expression quantification prior to and during treatment. This review focuses on the development of radio-labeled probes for imaging the following key proteins expressed during angiogenesis:vascular endothelial growth factor and its receptor integrin αvβ3, the extracellular domain of fibronectin, and matrix metalloproteases. This review also discusses the potential of these probes for individualized anti-angiogenesis therapy.

参考文献/References:

[1] Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation[J]. Cell, 2011, 144(5):646-674. DOI:10.1016/j.cell.2011.02.013.
[2] Moreno Garcia V, Basu B, Molife LR, et al. Combining antiangiogenics to overcome resistance:rationale and clinical experience[J]. Clin Cancer Res, 2012, 18(14):3750-3761. DOI:10.1158/1078-0432.CCR-11-1275.
[3] Eng L, Azad AK, Habbous S, et al.Vascular endothelial growth factor pathway polymorphisms as prognostic and pharmacogenetic factors in cancer:a systematic review and meta-analysis[J]. Clin Cancer Res, 2012,18(17):4526-4537. DOI:10.1158/1078-0432.CCR-12-1315.
[4] Desar IM, van Herpen CM, van Laarhoven HW, et al. Beyond RECIST:molecular and functional imaging techniques for evaluation of response to targeted therapy[J]. Cancer Treat Rev, 2009, 35(4):309-321. DOI:10.1016/j.ctrv.2008.12.001.
[5] 杨明福,李前伟. 肿瘤血管内皮生长因子受体核素显像研究现状[J].国际放射医学核医学杂志, 2010, 34(1):19-22. DOI:10.3760/cma.j.issn.1673-4114.2010.01.005. Yang MF,Li QW. Review present study on vascular endothelial growth factor receptor imaging[J]. Int J Radiat Med Nucl Med, 2010, 34(1):19-22.
[6] Cai W, Chen K, Mohamedali KA, et al. PET of vascular endothelial growth factor receptor expression[J]. J Nucl Med, 2006, 47(12):2048-2056.
[7] Lee I, Yoon KY, Kang CM, et al. Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using 64Cu-DOTA-VEGF121 and micro PET[J]. Nucl Med Biol, 2012, 39(6):840-846. DOI:10.1016/j.nucmedbio.2012.01.007.
[8] Blankenberg FG, Backer MV, Levashova Z, et al. In vivo tumor angiogenesis imaging with site-specific labeled 99mTc-HYNIC-VEGF[J]. Eur J Nucl Med Mol Imaging, 2006, 33(7):841-848. DOI:10.1007/s00259-006-0099-1.
[9] Levashova Z, Backer M, Hamby CV, et al. Molecular imaging of changes in the prevalence of vascular endothelial growth factor receptor in sunitinib-treated murine mammary tumors[J]. J Nucl Med, 2010, 51(6):959-966. DOI:10.2967/jnumed.109.072199.
[10] Blankenberg FG, Levashova Z, Sarkar SK, et al. Noninvasive assessment of tumor VEGF receptors in response to treatment with pazopanib:a molecular imaging study[J]. Transl Oncol, 2010, 3(1):56-64. DOI:10.1593/tlo.09271.
[11] Nagengast WB, Lub-De Hooge MN, Oosting SF, et al. VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment[J]. Cancer Res, 2011, 71(1):143-153. DOI:10.1158/0008-5472.CAN-10-1088.
[12] Meyer JP, Edwards KJ, Kozlowski P, et al. Selective imaging of VEGFR-1 and VEGFR-2 using 89Zr-labeled single-chain VEGF mutants[J]. J Nucl Med, 2016, 57(11):1811-1816. DOI:10.2967/jnumed.116.173237.
[13] Stollman TH, Scheer MG, Franssen GM, et al. Tumor accumulation of radiolabeled bevacizumab due to targeting of cell-and matrix-associated VEGF-A isoforms[J]. Cancer Biother Radiopharm, 2009, 24(2):195-200. DOI:10.1089/cbr.2008.0574.
[14] Scheer MG, Stollman TH, Boerman OC, et al. Imaging liver metastases of colorectal cancer patients with radiolabelled bevacizumab:Lack of correlation with VEGF-A expression[J]. Eur J Cancer, 2008, 44(13):1835-1840. DOI:10.1016/j.ejca.2008.05.026.
[15] 邵国强, 王自正. 整合素αvβ3受体靶向肿瘤显像研究进展[J].国际放射医学核医学杂志, 2014, 38(1):33-36. DOI:10.3760/cma.j.issn.1673-4114.2014.01.007. Shao GQ, Wang ZZ. Integrin αvβ3 targeted tumor imaging[J]. Int J Radiat Med Nucl Med, 2014, 38(1):33-36.
[16] Axelsson R, Bach-Gansmo T, Castell-Conesa J, et al. An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αvβ3-selective angiogenesis imaging agent 99mTc-NC100692[J]. Acta Radiol, 2010,51(1):40-46. DOI:10.3109/02841850903273974.
[17] Weis SM, Cheresh DA. αv integrins in angiogenesis and cancer[J/OL]. Cold Spring Harb Perspect Med, 2011, 1(1):a006478[2017-01-01]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234453/.DOI:10.1101/cshperspect.a006478.
[18] 岳宁, 袁双虎, 杨国仁. RGD分子影像在肺癌的研究现状与进展[J].中国肺癌杂志, 2014, 17(12):855-858. DOI:10.3779/j.issn.1009-3419.2014.12.06. Yue N, Yuan SH, Yang GR. Status and advances of RGD molecular imaging in lung cancer[J]. Chin J Lung Cancer, 2014, 17(12):855-858.
[19] 邵国强, 杨瑞, 梁凯, 等. 99Tcm-3P4-RGD2 microSPECT/CT显像评价抗新生血管治疗肿瘤疗效价值的实验研究[J]. 中华放射医学与防护杂志, 2017, 37(1):12-18. DOI:10.3760/cma.j.issn.0254-5098.2017.01.003. Shao GQ, Yang R, Liang K. Study on 99Tcm-3P4-RGD2 micro SPECT/CT imaging to anti-angiogensis therapeutic effect[J]. Chin J Radiol Med Prot, 2017, 37(1):12-18.
[20] Haubner R, Weber WA, Beer AJ, et al. Noninvasive visualization of the activated alphavbeta3 integrin in cancer patients by positron emission tomography and 18F Galacto-RGD[J/OL]. PLoS One, 2005, 2(3):e70[2017-05-01].http://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.0020070&type=printable.DOI:10.1371/journal.pmed.0020070.
[21] Chen H, Niu G, Wu H, et al. Clinical application of radiolabeled RGD peptides for PET imaging of integrin αvβ3[J]. Theranostics,2016, 6(1):78-92. DOI:10.7150/thno.13242.
[22] Doss M, Kolb HC, Zhang JJ, et al. Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans[J]. J Nucl Med, 2012, 53(5):787-795. DOI:10.2967/jnumed.111.088955.
[23] Battle MR, Goggi JL, Allen L, et al.Monitoring tumor response to antiangiogenic sunitinib therapy with 18F-fluciclatide, an 18F-labeled αvβ3-integrin and αvβ5-integrin imaging agent[J]. J Nucl Med,2011, 52(3):424-430. DOI:10.2967/jnumed.110.077479.
[24] Janssen ML, Oyen WJ, Dijkgraaf I, et al. Tumor targeting with radiolabeled αvβ3 integrin binding peptides in a nude mouse model[J]. Cancer Res, 2002, 62(21):6146-6151.
[25] Liu S. Radiolabeled cyclic RGD peptide bioconjugates as radiotracers targeting multiple integrins[J]. Bioconjug Chem, 2015, 26(8):1413-1438. DOI:10.1021/acs.bioconjchem.5b00327.
[26] Wang K, Seo BR, Fischbach C, et al. Fibronectin mechanobiology regulates tumorigenesis[J]. Cell Mol Bioeng, 2016, 9:1-11. DOI:10.1007/s12195-015-0417-4.
[27] Berndorff D, Borkowski S, Moosmayer D, et al. Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B fibronectin antibody fragments[J]. J Nucl Med, 2006, 47(10):1707-1716.
[28] Yoshimoto M, Kurihara H, Fujii H, et al. Theragnostic imaging using radiolabeled antibodies and tyrosine kinase inhibitors[J/OL]. Scientific World J, 2015, 2015:842101[2017-05-01]. https://www.researchgate.net/publication/276159365_Theragnostic_Imaging_Using_Radiolabeled_Antibodies_and_Tyrosine_Kinase_Inhibitors.DOI:10.1155/2015/842101.
[29] Jung KH, Lee KH. Molecular imaging in the era of personalized medicine[J]. J Pathol Transl Med, 2015, 49(1):5-12. DOI:10.4132/jptm.2014.10.24.
[30] Mees G, Dierckx R, Mertens K, et al. 99mTc-labeled t ricarbonyl his-CNA35 as an imaging agent for the detection of tumor vasculature[J]. J Nucl Med, 2012, 53(3):464-471. DOI:10.2967/jnumed.111. 095794.

相似文献/References:

[1]黄建敏,解朋,刘晓梅,等.以整合素αvβ3为靶点的肿瘤分子显像及靶向治疗[J].国际放射医学核医学杂志,2015,39(3):256.[doi:10.3760/cma.j.issn.1673-4114.2015.03.015]
 Huang Jianmin,Xie Peng,Liu Xiaomei,et al.Integrins αvβ3 in molecular imaging and targeted therapy of neoplasms[J].International Journal of Radiation Medicine and Nuclear Medicine,2015,39(5):256.[doi:10.3760/cma.j.issn.1673-4114.2015.03.015]
[2]邵国强,王自正.整合素αvβ3受体靶向肿瘤显像研究进展[J].国际放射医学核医学杂志,2014,38(1):33.[doi:10.3760/cma.j.issn 1673-4114.2014.01.007]
 Shao Guoqiang,Wang Zizheng.Integrin αvβ3 targeted tumor imaging[J].International Journal of Radiation Medicine and Nuclear Medicine,2014,38(5):33.[doi:10.3760/cma.j.issn 1673-4114.2014.01.007]
[3]郝玉美,贺欣,宋娜玲.靶向肿瘤新生血管整合素αvβ3受体显像研究现状及进展[J].国际放射医学核医学杂志,2014,38(3):179.[doi:10.3760/cma.j.issn.1673-4114.2014.03.010]
 Hao Yumei,He Xin,Song Naling.Progress on tumor angiogenesis imaging targeting integrin αvβ3 receptor[J].International Journal of Radiation Medicine and Nuclear Medicine,2014,38(5):179.[doi:10.3760/cma.j.issn.1673-4114.2014.03.010]
[4]赵龙,罗作明,孙龙,等.新型αvβ3和Neuropilin-1双靶点正电子成像探针18F-FAl-NOTA-RGD-ATWLPPR用于脑胶质瘤的PET显像研究[J].国际放射医学核医学杂志,2017,41(4):233.[doi:10.3760/cma.j.issn.1673-4114.2017.04.001]
 Zhao Long,Luo Zuoming,Sun Long,et al.Imaging of glioma with an integrin αvβ3 and neuropilin-1 dual-targeted PET probe 18F-FAl-NOTA-RGD-ATWLPPR[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(5):233.[doi:10.3760/cma.j.issn.1673-4114.2017.04.001]

备注/Memo

备注/Memo:
收稿日期:2017-05-11。
基金项目:河北财政厅优秀人才项目(361005)
通讯作者:刘晓梅,Email:ky121@163.com
更新日期/Last Update: 2017-09-25