[1]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):179-184.[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(3):179-184.[doi:10.3760/cma.j.issn.1673-4114.2014.03.010]
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靶向肿瘤新生血管整合素αvβ3受体显像研究现状及进展(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
38
期数:
2014年第3期
页码:
179-184
栏目:
出版日期:
2014-05-25

文章信息/Info

Title:
Progress on tumor angiogenesis imaging targeting integrin αvβ3 receptor
作者:
郝玉美;  贺欣;  宋娜玲
300192 天津, 北京协和医学院中国医学科学院放射医学研究所, 天津市放射医学与分子核医学重点实验室
Author(s):
Hao Yumei;  He Xin;  Song Naling
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300192, China
关键词:
新生血管化; 病理性; 整合素αvβ3; 放射性核素显像
Keywords:
Neovascularization; pathologic; Integrin αvβ3; Radionuclide imaging
DOI:
10.3760/cma.j.issn.1673-4114.2014.03.010
摘要:
恶性肿瘤的生长和转移依赖于肿瘤血管新生,研究发现整合素αvβ3高表达于肿瘤新生血管内皮细胞和部分肿瘤细胞表面,可通过介导细胞粘附来调控肿瘤血管新生,而整合素αvβ3在正常血管和组织表面不表达或呈低水平表达,据此可将其用作肿瘤新生血管显像和治疗的新靶点。近年来国内外关于整合素αvβ3靶向药物的设计、放射性核素的选择以及此类药物的最新研究内容有了较大进展,笔者将对如何更好地设计整合素αvβ3靶向药物、选择合适的放射性核素以及此类药物的研究方向进行综述。
Abstract:
Malignant tumors’growth and metastasis depend on tumor angiogenesis.Recent studies had found that the integrin αvβ3 had a high expression on the surface of tumor angiogenesis endothelial cells and parts of the tumor cells,it can regulate tumor angiogenesis by cell adhesion,but it does not ex-press on the surface of normal blood vessels or the normal organizations,or only had a low level expression.Thus it can be used as a new target for the tumor angiogenesis imaging and treatment.Recent years,there is a great progress on the design of the integrin αvβ3 targeting agents,the selection of radionuclides,and the latest research on the agents at home and abroad.This article will made a review on how to better design the integrin αvβ3 agents,choose the appropriate radionuclides,and the research direction of these agents.

参考文献/References:

[1] Liu S.Radiolabeled cyclic RGD peptides as integrin αvβ3-targeted radiotracers:maximizing binding affinity via bivalency[J].Biocon-jug Chem,2009,20(12):2199-2213.
[2] Herrmann K,Erkan M,Dobritz M,et al.Comparison of 3’-deoxy-3’-[18F]fluorothymidine positron emission tomography (FLT PET) and FDG PET/CT for the detection and characterization of pancreatic tumours[J].Eur J Nucl Med Mol Imaging,2012,39(5):846-851.
[3] Folkman J.Tumor angiogenesis:therapeutic implications[J].N Engl Med,1971,285(21):1182-1186.
[4] Hu XD,Xing LG,Yu JM.Nuclear medical molecular imaging of tu-mor angiogenesis:current status and future prospects[J].Chin Med J (Engl),2013,126(14):2741-2746.
[5] 刘开元,李前伟,刘广元.放射性标记RGD序列多肽与整合素αvβ3受体显像的研究进展[J].医学综述,2006,12(12):757-759.
[6] Max R,Gerritsen RR,Nooijen PT,et al.Immunohistochemical analysis of integrin αvβ3 expression on tumor-associated vessels of human carcinomas[J].Int J Cancer,1997,71(3):320-324.
[7] 王浩,施培基,周晓靓,等.RGD肽及其衍生物在肿瘤显像剂治疗中的研究进展[J].国际放射医学核医学杂志,2007,31(5):274-277.
[8] 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.
[9] Yu YP,Wang Q,Liu YC,et al.Molecular basis for the targeted binding of RGD-containing peptide to integrin alphaVbeta3[J].Biomaterials,2014,35(5):1667-1675.
[10] Alam IS,Witney TH,Tomasi G,et al.Radiolabeled RGD Tracer Kinetics Annotates Differential αvβ3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression[J/OL].Mol Imaging Biol,2013[2014-03-20].http://link.springer.com/article/10.1007%2Fs11307-013-0710-3. [published online ahead of print Dec 6,2013].
[11] Oxboel J,Brandt-Larsen M,Schjoeth-Eskesen C,et al.Comparison of two new angiogenesis PET tracers 68Ga-NODAGA-E[c (RGDyK)]2 and 64Cu-NODAGA-E[c (RGDyK)]2;in vivo imaging studies in hu-man xenograft tumors[J].Nucl Med Biol,2014,41(3):259-267.
[12] Maschauer S,Haubner R,Kuwert T,et al.18F-Glyco-RGD Peptides for PET Imaging of Integrin Expression:Efficient Radiosynthesis by Click Chemistry and Modulation of Biodistribution by Glycosyla-tion[J].Mol Pharm,2014,11(2):505-515.
[13] Jin ZH,Furukawa T,Sogawa C,et al.PET imaging and biodistribu-tion analysis of the effects of succinylated gelatin combined with Llysine on renal uptake and retention of Cu-cyclam-RAFT-c (-RGDfK-) in vivo[J].Eur J Pharm Biopharm,2013,86(3):478-486.
[14] Liu ZF,Niu G,Shi J,et al.68Ga-labeled cyclic RGD dimmers with Gly3 and PEG4 linkers:promising agents for tumor integrin αvβ3 PET imaging[J].Eur J Nucl Med Mol Imaging,2009,36(6):947-957.
[15] Jamous M,Haberkorn U,Mier W.Synthesis of peptide radiophar-maceuticals for the therapy and diagnosis of tumor diseases[J].Molecules,2013,18(3):3379-3409.
[16] Lewis MR,Kao JY,Anderson AL,el al.An improved method for conjugating monoclonal antibodies with N-hydroxysulfosuccin-imidyl DOTA[J].Bioconjug Chem,2001,12(2):320-324.
[17] Zhang Y,Hong H,Engle JW,et al.Positron emission tomography imaging of CD105 expression with a 64Cu-labeled monoclonal anti-body:NOTA is superior to DOTA[J/OL].PloS One,2011,6(12):e28005[2014-03-20].http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028005.
[18] Yapp DT,Ferreira CL,Gill RK,et al.Imaging tumor vasculature noninvasively with positron emission tomography and RGD pep-tides labeled with copper 64 using the bifunctonal chelates DOTA,oxo-DO3a.and PCTA[J].Mol Imaging,2013,12(4):263-272.
[19] 王荣福,李险峰,王强.SPECT/CT的最新应用进展[J].CT理论与应用研究,2012,21(3):577-582.
[20] 张春丽,杨铭,王荣福.RGD肽与整合素αvβ3受体结合的构效关系及放射性标记配体的设计[J].肿瘤学杂志,2009,15(1):76-81.
[21] Beer A J,Lorenzen S,Metz S,et al.Comparison of integrin αVβ3 ex-pression and glucose metabolism in primary and metastatic lesions in cancer patients:a PET study using 18F-galacto-RGD and 18F-FDG[J].J Nucl Med,2008,49(1):22-29.
[22] Sugiura G,Kuhn H,Sauter M,et al.Radiolabeling strategies for tu-mor-targeting proteinaceous drugs[J].Molecules,2014,19(2):2135-2165.
[23] Zhu Z,Yin Y,Zheng K,et al.Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using 68Ga-PRGD2 PET/CT:a prospective proof-of-concept cohort study[J].Ann Rheum Dis,2014,73(6):1269-1272.
[24] Trajkovic-Arsic M,Mohajerani P,Sarantopoulos A,et al.Multi-modal molecular imaging of integrin αvβ3 for in vivo detection of pancreatic cancer[J].J Nucl Med,2014,55(3):446-451.
[25] Durkan K,Jiang Z,Rold T L,et al.A heterodimeric[RGD-Glu-64[Cu-NO2A]-6-Ahx-RM2] αvβ3/GRPr-targeting antagonist radio-tracer for PET imaging of prostate tumors[J].Nucl Med Biol,2014,41(2):133-139.
[26] Shallal HM,Minn I,Banerjee SR,et al.Heterobivalent agents tar-geting PSMA and integrin-αvβ3[J].Bioconjug Chem,2014,25(2):393-405.
[27] Rangger C,Helbok A,Sosabowski J,et al.Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles[J].Int J Nanomedicine,2013,8:4659-4671.
[28] Debergh I,Van Damme N,De Naeyer D,et al.Molecular imaging of tumor-associated angiogenesis using a novel magnetic resonance imaging contrast agent targeting alphabeta integrin[J].Ann Surg Oncol,2013,21(6):2097-2104.
[29] Ma Q,Ji B,Jia B,et al.Differential diagnosis of solitary pulmonary nodules using 99mTc-3PI4-RGDF scintigraphy[J].Eur J Nucl Med Mol Imaging,2011,38(12):2145-2152.
[30] Zhao D,Jin X,Li F,et al.Integrin αvβ3 Imaging of Radioactive Iodine-Refractory Thyroid Cancer Using 99mTc-3PRGD2[J].J Nucl Med,2012,53(12):1872-1877.
[31] Zhu Z,Miao W,Li Q,et al.99mTc-3PRGD2 for integrin receptor imaging of lung cancer:a multicenter study[J].J Nucl Med,2012,53(5):716-722.
[32] Shi J,Fan D,Dong C,et al.Anti-tumor effect of integrin targeted 177Lu-3PRGD2 and combined therapy with endostar[J].Theranos-tics,2014,4(3):256-266.
[33] 贺欣,赵启仁,宋娜玲,等.肿瘤抑素T7肽及其衍生物T7-NGR载体构建及表达[J].生物工程,2008,12(3):240-244.
[34] 郝玉美,贺欣,周晓靓,等.99mTc标记T7肽及其在裸鼠非小细胞肺癌模型体内的生物分布研究[J].中国肺癌杂志,2014,17(3):189-196.

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备注/Memo

备注/Memo:
收稿日期:2014-03-20。
基金项目:国家自然科学基金(30970851);北京协和医学院协和青年科研基金(2012J06);中国医学科学院放射医学研究所发展基金(SF1306);中国医学科学院放射医学研究所探索基金(ST1313)
通讯作者:贺欣,Email:saluoo@163.com;宋娜玲,Email:nalingsong@sina.com
更新日期/Last Update: 1900-01-01