• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

用于正电子发射断层成像的用氟-18对单链血管内皮生长因子进行位点特异性标记

Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging.

作者信息

Wang Hui, Gao Haokao, Guo Ning, Niu Gang, Ma Ying, Kiesewetter Dale O, Chen Xiaoyuan

机构信息

Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

出版信息

Theranostics. 2012;2(6):607-17. doi: 10.7150/thno.4611. Epub 2012 Jun 15.

DOI:10.7150/thno.4611
PMID:22768028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3388593/
Abstract

UNLABELLED

Vascular endothelial growth factor (VEGF) is one of the most important mediators of angiogenesis. Single-chain (sc)-VEGF protein containing an N-terminal Cys-tag has been designed for site-specific modification with a variety of imaging and therapeutic moieties. Site-specific labeling of scVEGF with thiol-reactive prosthetic group, N-[2-(4-(18)F-fluorobenzamido) ethyl] maleimide ([(18)F]FBEM) for positron emission tomography (PET) imaging of VEFGR may provide a new tracer which has great potential for clinical translation.

METHODS

[(18)F]FBEM-scVEGF was synthesized by site-specific conjugation of (18)F-FBEM to a thiol group in Cys-tag of scVEGF at room temperature. The functional activity after labeling was tested by immunofluorescence staining, cellular uptake and efflux. The tumor targeting and in vivo properties were evaluated by biodistribution and microPET studies in tumor-bearing mice.

RESULTS

The radiolabeling yield and specific activity of [(18)F]FBEM-scVEGF were 20.6 ± 15.1% (based on starting [(18)F]FBEM, uncorrected, n = 5) and 58.8 ± 12.4 GBq/µmol, respectively. Noninvasive microPET and direct tissue sampling experiments demonstrated that [(18)F]FBEM-scVEGF had VEGFR specific tumor uptake in MDA-MB-435, U87MG and 4T1 xenograft models. The optimal tumor uptake was achieved at 2 h p.i., which can be partially, but significantly blocked by co-injection of non-labeled scVEGF protein. Overall, [(18)F]FBEM-scVEGF showed VEGFR specific tumor uptake.

CONCLUSION

The scVEGF was site-specifically labeled with (18)F via [(18)F]FBEM prosthetic group and the tracer [(18)F]FBEM-scVEGF exhibited high receptor binding affinity and tumor targeting efficacy. Further study of [(18)F] FBEM-scVEGF to evaluate angiogenesis in cancer and other disease types is warranted.

摘要

未标记

血管内皮生长因子（VEGF）是血管生成最重要的介质之一。含N端半胱氨酸标签的单链（sc）-VEGF蛋白已被设计用于与多种成像和治疗部分进行位点特异性修饰。用硫醇反应性辅基N-[2-(4-(18)F-氟苯甲酰胺基)乙基]马来酰亚胺（[(18)F]FBEM）对scVEGF进行位点特异性标记以用于VEGFR的正电子发射断层扫描（PET）成像，可能会提供一种具有巨大临床转化潜力的新型示踪剂。

方法

[(18)F]FBEM-scVEGF通过在室温下将(18)F-FBEM与scVEGF半胱氨酸标签中的硫醇基团进行位点特异性偶联而合成。标记后的功能活性通过免疫荧光染色、细胞摄取和流出进行测试。通过在荷瘤小鼠中的生物分布和微型PET研究评估肿瘤靶向性和体内特性。

结果

[(18)F]FBEM-scVEGF的放射性标记产率和比活分别为20.6±15.1%（基于起始[(18)F]FBEM，未校正，n = 5）和58.8±12.4 GBq/µmol。无创微型PET和直接组织采样实验表明，[(18)F]FBEM-scVEGF在MDA-MB-435、U87MG和4T1异种移植模型中具有VEGFR特异性肿瘤摄取。最佳肿瘤摄取在注射后2小时达到，可通过共同注射未标记的scVEGF蛋白部分但显著地被阻断。总体而言，[(18)F]FBEM-scVEGF显示出VEGFR特异性肿瘤摄取。

结论

scVEGF通过[(18)F]FBEM辅基被(18)F位点特异性标记，示踪剂[(18)F]FBEM-scVEGF表现出高受体结合亲和力和肿瘤靶向效能。对[(18)F]FBEM-scVEGF进行进一步研究以评估癌症和其他疾病类型中的血管生成是有必要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/60387d06d2db/thnov02p0607g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/1808e247a183/thnov02p0607g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/6653c24cc947/thnov02p0607g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/a842e56d85c4/thnov02p0607g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/f8706ba47c6b/thnov02p0607g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/60387d06d2db/thnov02p0607g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/1808e247a183/thnov02p0607g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/6653c24cc947/thnov02p0607g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/a842e56d85c4/thnov02p0607g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/f8706ba47c6b/thnov02p0607g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c0/3388593/60387d06d2db/thnov02p0607g05.jpg

相似文献

1
Site-Specific Labeling of scVEGF with Fluorine-18 for Positron Emission Tomography Imaging.用于正电子发射断层成像的用氟-18对单链血管内皮生长因子进行位点特异性标记
Theranostics. 2012;2(6):607-17. doi: 10.7150/thno.4611. Epub 2012 Jun 15.
2
A thiol-reactive 18F-labeling agent, N-[2-(4-18F-fluorobenzamido)ethyl]maleimide, and synthesis of RGD peptide-based tracer for PET imaging of alpha v beta 3 integrin expression.一种硫醇反应性18F标记剂，N-[2-(4-18F-氟苯甲酰胺基)乙基]马来酰亚胺，以及用于αvβ3整合素表达PET成像的基于RGD肽的示踪剂的合成。
J Nucl Med. 2006 Jul;47(7):1172-80.
3
ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [68Ga]PET imaging of VEGF receptors in angiogenic vasculature.ScVEGF-PEG-HBED-CC 和 scVEGF-PEG-NOTA 缀合物：用于血管生成血管中 VEGF 受体的 [68Ga]PET 成像的易于标记重组蛋白的比较。
Nucl Med Biol. 2010 May;37(4):405-12. doi: 10.1016/j.nucmedbio.2010.02.001. Epub 2010 Apr 7.
4
PET of insulinoma using ¹⁸F-FBEM-EM3106B, a new GLP-1 analogue.¹⁸F-FBEM-EM3106B 用于胰岛素瘤的 PET 显像，这是一种新型 GLP-1 类似物。
Mol Pharm. 2011 Oct 3;8(5):1775-82. doi: 10.1021/mp200141x. Epub 2011 Aug 19.
5
PET of EGFR expression with an 18F-labeled affibody molecule.用 18F 标记的亲和体分子进行表皮生长因子受体的 PET 显像。
J Nucl Med. 2012 Jul;53(7):1110-8. doi: 10.2967/jnumed.111.100842. Epub 2012 Jun 11.
6
PET imaging of EGF receptors using [18F]FBEM-EGF in a head and neck squamous cell carcinoma model.使用 [18F]FBEM-EGF 通过 PET 成像对头颈部鳞状细胞癌模型中的表皮生长因子受体进行成像。
Eur J Nucl Med Mol Imaging. 2012 Feb;39(2):300-8. doi: 10.1007/s00259-011-1969-8. Epub 2011 Nov 23.
7
Selective Imaging of VEGFR-1 and VEGFR-2 Using 89Zr-Labeled Single-Chain VEGF Mutants.使用89Zr标记的单链VEGF突变体对VEGFR-1和VEGFR-2进行选择性成像。
J Nucl Med. 2016 Nov;57(11):1811-1816. doi: 10.2967/jnumed.116.173237. Epub 2016 Jul 7.
8
Ga--bis[2-Hydroxy-5-(carboxyethyl)benzyl]ethylenediamine--diacetic acid-polyethylene glycol-single-chain Cys-tagged vascular endothelial growth factor-121镓-双[2-羟基-5-(羧乙基)苄基]乙二胺-二乙酸-聚乙二醇-单链半胱氨酸标记的血管内皮生长因子-121
9
Development of a new thiol site-specific prosthetic group and its conjugation with [Cys(40)]-exendin-4 for in vivo targeting of insulinomas.开发一种新的硫醇位点特异性的 prosthetic group 并将其与 [Cys(40)]-exendin-4 缀合，用于胰岛素瘤的体内靶向。
Bioconjug Chem. 2013 Jul 17;24(7):1191-200. doi: 10.1021/bc400084u. Epub 2013 Jun 28.
10
scVEGF microbubble ultrasound contrast agents: a novel probe for ultrasound molecular imaging of tumor angiogenesis.scVEGF 微泡超声对比剂：一种用于肿瘤血管生成超声分子成像的新型探针。
Invest Radiol. 2010 Oct;45(10):579-85. doi: 10.1097/RLI.0b013e3181efd581.

引用本文的文献

1
Tumor angiogenesis targeting and imaging using gold nanoparticle probe with directly conjugated cyclic NGR.使用直接偶联环NGR的金纳米颗粒探针进行肿瘤血管生成靶向与成像
RSC Adv. 2018 Jan 5;8(3):1706-1716. doi: 10.1039/c7ra10155d. eCollection 2018 Jan 2.
2
A novel strategy for site selective spin-labeling to investigate bioactive entities by DNP and EPR spectroscopy.一种通过 DNP 和 EPR 光谱研究生物活性实体的新型定点自旋标记策略。
Sci Rep. 2021 Jul 1;11(1):13714. doi: 10.1038/s41598-021-92975-6.
3
The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy.

本文引用的文献

1
Photosensitizer-conjugated gold nanorods for enzyme-activatable fluorescence imaging and photodynamic therapy.用于酶激活荧光成像和光动力疗法的光敏剂共轭金纳米棒
Theranostics. 2012;2(2):190-7. doi: 10.7150/thno.3478. Epub 2012 Feb 11.
2
Lasting controversy on ranibizumab and bevacizumab.雷珠单抗和贝伐单抗的持久争议。
Theranostics. 2011;1:395-402. doi: 10.7150/thno/v01p0395. Epub 2011 Dec 12.
3
Radiosynthesis of [11C]Vandetanib and [11C]chloro-Vandetanib as new potential PET agents for imaging of VEGFR in cancer.[11C]凡德他尼和[11C]氯凡德他尼的放射性合成作为用于癌症中 VEGFR 成像的新型潜在 PET 剂。
血管内皮生长因子受体作为核医学中癌症诊断与联合治疗分子靶点的作用
Cancers (Basel). 2021 Mar 3;13(5):1072. doi: 10.3390/cancers13051072.
4
Imaging Early-Stage Metastases Using an F-Labeled VEGFR-1-Specific Single Chain VEGF Mutant.使用 F 标记的 VEGFR-1 特异性单链 VEGF 突变体进行早期转移成像。
Mol Imaging Biol. 2021 Jun;23(3):340-349. doi: 10.1007/s11307-020-01555-z. Epub 2020 Nov 6.
5
PET Imaging of VEGFR with a Novel Cu-Labeled Peptide.用新型铜标记肽对血管内皮生长因子受体进行正电子发射断层显像
ACS Omega. 2020 Apr 8;5(15):8508-8514. doi: 10.1021/acsomega.9b03953. eCollection 2020 Apr 21.
6
Polydopamine-coated gold nanostar for combined antitumor and antiangiogenic therapy in multidrug-resistant breast cancer.聚多巴胺包覆的金纳米星用于多药耐药乳腺癌的联合抗肿瘤和抗血管生成治疗。
Nanotheranostics. 2019 Jun 6;3(3):266-283. doi: 10.7150/ntno.36842. eCollection 2019.
7
Direct measurements of VEGF-VEGFR2 binding affinities reveal the coupling between ligand binding and receptor dimerization.直接测量 VEGF-VEGFR2 结合亲和力揭示了配体结合与受体二聚化之间的偶联。
J Biol Chem. 2019 Jun 7;294(23):9064-9075. doi: 10.1074/jbc.RA119.007737. Epub 2019 Apr 25.
8
Pharmacokinetic analysis reveals limitations and opportunities for nanomedicine targeting of endothelial and extravascular compartments of tumours.药代动力学分析揭示了纳米医学靶向肿瘤内皮和血管外腔的局限性和机遇。
J Drug Target. 2019 Jun-Jul;27(5-6):690-698. doi: 10.1080/1061186X.2019.1566339. Epub 2019 Feb 4.
9
Design, Synthesis, and Biological Evaluation of Axitinib Derivatives.阿昔替尼衍生物的设计、合成与生物评价。
Molecules. 2018 Mar 23;23(4):747. doi: 10.3390/molecules23040747.
10
Fast indirect fluorine-18 labeling of protein/peptide using the useful 6-fluoronicotinic acid-2,3,5,6-tetrafluorophenyl prosthetic group: A method comparable to direct fluorination.使用有用的6-氟烟酸-2,3,5,6-四氟苯基辅助基团对蛋白质/肽进行快速间接氟-18标记：一种可与直接氟化相媲美的方法。
J Labelled Comp Radiopharm. 2017 Mar;60(3):168-175. doi: 10.1002/jlcr.3487. Epub 2017 Feb 1.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3222-6. doi: 10.1016/j.bmcl.2011.04.049. Epub 2011 Apr 20.
4
F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging.F 标记的 GRPR 激动剂和拮抗剂：前列腺癌成像中的比较研究。
Theranostics. 2011;1:220-9. doi: 10.7150/thno/v01p0220.
5
VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment.VEGF-PET 成像技术是一种无创生物标志物，可显示舒尼替尼治疗期间肿瘤的差异变化。
Cancer Res. 2011 Jan 1;71(1):143-53. doi: 10.1158/0008-5472.CAN-10-1088. Epub 2010 Nov 17.
6
Automated radiochemical synthesis of [18F]FBEM: a thiol reactive synthon for radiofluorination of peptides and proteins.[18F]FBEM的自动化放射化学合成：一种用于肽和蛋白质放射性氟化的硫醇反应性合成子。
Appl Radiat Isot. 2011 Feb;69(2):410-4. doi: 10.1016/j.apradiso.2010.09.023. Epub 2010 Oct 8.
7
scVEGF microbubble ultrasound contrast agents: a novel probe for ultrasound molecular imaging of tumor angiogenesis.scVEGF 微泡超声对比剂：一种用于肿瘤血管生成超声分子成像的新型探针。
Invest Radiol. 2010 Oct;45(10):579-85. doi: 10.1097/RLI.0b013e3181efd581.
8
ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [68Ga]PET imaging of VEGF receptors in angiogenic vasculature.ScVEGF-PEG-HBED-CC 和 scVEGF-PEG-NOTA 缀合物：用于血管生成血管中 VEGF 受体的 [68Ga]PET 成像的易于标记重组蛋白的比较。
Nucl Med Biol. 2010 May;37(4):405-12. doi: 10.1016/j.nucmedbio.2010.02.001. Epub 2010 Apr 7.
9
Synthesis and preclinical evaluation of [(11)C]PAQ as a PET imaging tracer for VEGFR-2.[(11)C]PAQ作为VEGFR-2的PET成像示踪剂的合成及临床前评估
Eur J Nucl Med Mol Imaging. 2009 Aug;36(8):1283-95. doi: 10.1007/s00259-009-1111-3. Epub 2009 Mar 14.
10
Quantitative PET imaging of VEGF receptor expression.血管内皮生长因子受体表达的定量正电子发射断层成像
Mol Imaging Biol. 2009 Jan-Feb;11(1):15-22. doi: 10.1007/s11307-008-0172-1. Epub 2008 Sep 11.