• 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

（R）-和（S）-2-氨基-5-[（18）F]氟-2-甲基戊酸（（R）-、（S）-[(18)F]FAMPe）作为脑肿瘤潜在正电子发射断层显像剂的合成、放射性标记及生物学评价

Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[(18)F]fluoro-2-methylpentanoic Acid ((R)-, (S)-[(18)F]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors.

作者信息

Bouhlel Ahlem, Zhou Dong, Li Aixiao, Yuan Liya, Rich Keith M, McConathy Jonathan

机构信息

†Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.

出版信息

J Med Chem. 2015 May 14;58(9):3817-29. doi: 10.1021/jm502023y. Epub 2015 May 4.

DOI:10.1021/jm502023y
PMID:25843369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4476065/
Abstract

A novel (18)F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[(18)F]fluoro-2-methylpentanoic acid ([(18)F]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [(18)F]FAMPe were obtained in good radiochemical yield (24-52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that (S)-[(18)F]FAMPe enters cells partly via sodium-independent system L transporters and also via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and small animal PET/CT studies in the mouse DBT model of glioblastoma showed that both (R)- and (S)-[(18)F]FAMPe have good tumor imaging properties with the (S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Comparison of the SUVs showed that (S)-[(18)F]FAMPe had higher tumor to brain ratios compared to (S)-[(18)F]FET, a well-established system L substrate.

摘要

一种新型的基于α,α-二取代氨基酸的（18）F标记示踪剂，2-氨基-5-[(18)F]氟-2-甲基戊酸（[(18)F]FAMPe）已被开发用于脑肿瘤成像，其烷基侧链比先前报道的化合物更长，通过系统L氨基酸转运增加脑内摄取。[(18)F]FAMPe的两种对映体均以良好的放射化学产率（24 - 52%，n = 8）和高放射化学纯度（>99%）获得。在小鼠DBT胶质瘤细胞中的体外摄取实验表明，（S）-[(18)F]FAMPe部分通过不依赖钠的系统L转运体进入细胞，也通过其他非系统A转运系统进入细胞，包括识别谷氨酰胺的转运体。在胶质母细胞瘤小鼠DBT模型中的生物分布和小动物PET/CT研究表明，（R）-和（S）-[(18)F]FAMPe均具有良好的肿瘤成像特性，其中（S）-对映体具有更高的肿瘤摄取和肿瘤与脑比值。SUVs的比较表明，与成熟的系统L底物（S）-[(18)F]FET相比，（S）-[(18)F]FAMPe具有更高的肿瘤与脑比值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/da1a188fa979/nihms693311f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/83e3bfe1984b/nihms693311f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/5f52ad9cc126/nihms693311f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/c19b0b1e8dfb/nihms693311f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/16275c45c06e/nihms693311f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/9e958d493c6e/nihms693311f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/f2a3dfe08850/nihms693311f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/8c3cfaa70545/nihms693311f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/f41be4da5281/nihms693311f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/6e4a7bb25d88/nihms693311f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/1d8931775b22/nihms693311f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/9266d62897da/nihms693311f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/da1a188fa979/nihms693311f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/83e3bfe1984b/nihms693311f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/5f52ad9cc126/nihms693311f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/c19b0b1e8dfb/nihms693311f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/16275c45c06e/nihms693311f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/9e958d493c6e/nihms693311f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/f2a3dfe08850/nihms693311f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/8c3cfaa70545/nihms693311f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/f41be4da5281/nihms693311f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/6e4a7bb25d88/nihms693311f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/1d8931775b22/nihms693311f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/9266d62897da/nihms693311f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f27d/4476065/da1a188fa979/nihms693311f12.jpg

相似文献

1
Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[(18)F]fluoro-2-methylpentanoic Acid ((R)-, (S)-[(18)F]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors.（R）-和（S）-2-氨基-5-[（18）F]氟-2-甲基戊酸（（R）-、（S）-[(18)F]FAMPe）作为脑肿瘤潜在正电子发射断层显像剂的合成、放射性标记及生物学评价
J Med Chem. 2015 May 14;58(9):3817-29. doi: 10.1021/jm502023y. Epub 2015 May 4.
2
Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).α-甲基与α-氢取代对用于正电子发射断层扫描（PET）的庚酸[F-18]氟烷基氨基酸的脑摄取及肿瘤成像特性的影响
J Med Chem. 2016 Apr 14;59(7):3515-31. doi: 10.1021/acs.jmedchem.6b00189. Epub 2016 Mar 23.
3
Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model.在脑肿瘤荷瘤动物模型中评估F-18标记的氨基酸衍生物和[18F]FDG作为正电子发射断层扫描（PET）探针的情况。
Nucl Med Biol. 2005 May;32(4):367-75. doi: 10.1016/j.nucmedbio.2005.01.005.
4
Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.¹⁸F 标记的氟丙基色氨酸类似物的合成与生物评价作为肿瘤成像的潜在 PET 探针。
Eur J Med Chem. 2013;70:768-80. doi: 10.1016/j.ejmech.2013.10.054. Epub 2013 Oct 30.
5
Synthesis and preliminary biological evaluation of S-11C-methyl-D-cysteine as a new amino acid PET tracer for cancer imaging.新型氨基酸PET肿瘤显像剂S-11C-甲基-D-半胱氨酸的合成及初步生物学评价
Amino Acids. 2015 Apr;47(4):719-27. doi: 10.1007/s00726-014-1899-4. Epub 2014 Dec 23.
6
18F-AFETP, 18F-FET, and 18F-FDG imaging of mouse DBT gliomas.18F-AFETP、18F-FET 和 18F-FDG 对小鼠 DBT 脑胶质瘤的成像研究。
J Nucl Med. 2013 Jul;54(7):1120-6. doi: 10.2967/jnumed.112.113217. Epub 2013 May 6.
7
Radiosynthesis and biological evaluation of alpha-[F-18]fluoromethyl phenylalanine for brain tumor imaging.alpha-[F-18]氟甲基苯丙氨酸的放射合成与脑肿瘤成像的生物学评价。
Nucl Med Biol. 2013 May;40(4):498-506. doi: 10.1016/j.nucmedbio.2012.12.013. Epub 2013 Mar 23.
8
System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid.靶向氨基酸转运的脑和全身肿瘤PET显像剂2-氨基-3-[(18)F]氟-2-甲基丙酸和3-[(18)F]氟-2-甲基-2-(甲氨基)丙酸。
Nucl Med Biol. 2015 Jan;42(1):8-18. doi: 10.1016/j.nucmedbio.2014.07.002. Epub 2014 Aug 1.
9
Radiosynthesis and Preclinical Evaluation of -[F]FET and [F]FET-OMe as Novel [F]FET Analogs for Brain Tumor Imaging.正电子发射断层扫描放射性药物合成与预临床评价：新型 [F]FET 类似物 -[F]FET 和 [F]FET-OMe 用于脑肿瘤成像。
Mol Pharm. 2024 Jun 3;21(6):2795-2812. doi: 10.1021/acs.molpharmaceut.3c01215. Epub 2024 May 15.
10
(R,S)-anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid: synthesis from racemic 2-benzyloxycyclopentanone and biological evaluation for brain tumor imaging with positron emission tomography.(R,S)-反式-1-氨基-2-[18F]氟环戊基-1-羧酸：从外消旋 2-苄氧基环戊酮合成及正电子发射断层扫描用于脑肿瘤成像的生物学评价。
J Med Chem. 2010 Sep 23;53(18):6603-7. doi: 10.1021/jm100841m.

引用本文的文献

1
Synthetic F labeled biomolecules that are selective and promising for PET imaging: major advances and applications.用于正电子发射断层扫描（PET）成像具有选择性且前景广阔的合成F标记生物分子：主要进展与应用
RSC Med Chem. 2024 Apr 17;15(6):1899-1920. doi: 10.1039/d4md00033a. eCollection 2024 Jun 19.
2
Design, Synthesis, and Biological Evaluation of a Novel [F]-Labeled Arginine Derivative for Tumor Imaging.一种用于肿瘤成像的新型[F]标记精氨酸衍生物的设计、合成及生物学评价
Pharmaceuticals (Basel). 2023 Oct 16;16(10):1477. doi: 10.3390/ph16101477.
3
Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains.

本文引用的文献

1
Glutamine-based PET imaging facilitates enhanced metabolic evaluation of gliomas in vivo.基于谷氨酰胺的正电子发射断层扫描（PET）成像有助于在体内增强对胶质瘤的代谢评估。
Sci Transl Med. 2015 Feb 11;7(274):274ra17. doi: 10.1126/scitranslmed.aaa1009.
2
System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid.靶向氨基酸转运的脑和全身肿瘤PET显像剂2-氨基-3-[(18)F]氟-2-甲基丙酸和3-[(18)F]氟-2-甲基-2-(甲氨基)丙酸。
Nucl Med Biol. 2015 Jan;42(1):8-18. doi: 10.1016/j.nucmedbio.2014.07.002. Epub 2014 Aug 1.
3
《间谍游戏：氟原子在氨基酸侧链中扮演的多样角色》。
Molecules. 2023 Aug 22;28(17):6192. doi: 10.3390/molecules28176192.
4
Radiolabeling and Biological Evaluation of Novel Tc-Nitrido and Tc-Oxo Complexes with 4-Methoxy--Phenylalanine Dithiocarbamate for Tumor Imaging.新型锝-氮化物和锝-氧化物配合物与4-甲氧基-苯丙氨酸二硫代氨基甲酸盐用于肿瘤成像的放射性标记及生物学评价
Pharmaceutics. 2022 Oct 15;14(10):2196. doi: 10.3390/pharmaceutics14102196.
5
The Utility of Conventional Amino Acid PET Radiotracers in the Evaluation of Glioma Recurrence also in Comparison with MRI.传统氨基酸PET放射性示踪剂在评估胶质瘤复发中的应用以及与MRI的比较。
Diagnostics (Basel). 2022 Mar 29;12(4):844. doi: 10.3390/diagnostics12040844.
6
A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma.探讨脑胶质瘤影像诊断与治疗用放射性药物需求的观点。
Theranostics. 2021 Jul 6;11(16):7911-7947. doi: 10.7150/thno.56639. eCollection 2021.
7
F-Branched-Chain Amino Acids: Structure-Activity Relationships and PET Imaging Potential.支链氨基酸：结构-活性关系及正电子发射断层扫描成像潜力。
J Nucl Med. 2019 Jul;60(7):1003-1009. doi: 10.2967/jnumed.118.220483. Epub 2019 Jan 25.
8
Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).α-甲基与α-氢取代对用于正电子发射断层扫描（PET）的庚酸[F-18]氟烷基氨基酸的脑摄取及肿瘤成像特性的影响
J Med Chem. 2016 Apr 14;59(7):3515-31. doi: 10.1021/acs.jmedchem.6b00189. Epub 2016 Mar 23.
Imaging tumour ATB0,+ transport activity by PET with the cationic amino acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine.
用正电子发射断层扫描（PET）和带正电荷的氨基酸 O-2-((2-[18F]氟乙基)甲基-氨基)乙基酪氨酸（[18F]FETME）来观察肿瘤的氨基酸摄取转运活性。
Mol Imaging Biol. 2014 Jun;16(3):412-20. doi: 10.1007/s11307-013-0711-2. Epub 2013 Dec 5.
4
Differences in transport mechanisms of trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in inflammation, prostate cancer, and glioma cells: comparison with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose.反式-1-氨基-3-[18F]氟环丁烷羧酸在炎症、前列腺癌和神经胶质瘤细胞中的转运机制差异：与 L-[甲基-11C]蛋氨酸和 2-脱氧-2-[18F]氟-D-葡萄糖的比较。
Mol Imaging Biol. 2014 Jun;16(3):322-9. doi: 10.1007/s11307-013-0693-0.
5
Comparative evaluation of transport mechanisms of trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid and L-[methyl-¹¹C]methionine in human glioma cell lines.比较研究反式-1-氨基-3-[¹⁸F]氟环丁烷羧酸和 L-[甲基-¹¹C]蛋氨酸在人神经胶质瘤细胞系中的转运机制。
Brain Res. 2013 Oct 16;1535:24-37. doi: 10.1016/j.brainres.2013.08.037. Epub 2013 Aug 27.
6
18F-AFETP, 18F-FET, and 18F-FDG imaging of mouse DBT gliomas.18F-AFETP、18F-FET 和 18F-FDG 对小鼠 DBT 脑胶质瘤的成像研究。
J Nucl Med. 2013 Jul;54(7):1120-6. doi: 10.2967/jnumed.112.113217. Epub 2013 May 6.
7
Fluorine-18 labeled amino acids for oncologic imaging with positron emission tomography.正电子发射断层扫描用氟-18 标记的氨基酸肿瘤显像剂
Curr Top Med Chem. 2013;13(8):871-91. doi: 10.2174/1568026611313080002.
8
Characterization of primary prostate carcinoma by anti-1-amino-2-[(18)F] -fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F] FACBC) uptake.通过抗1-氨基-2-[(18)F]-氟环丁烷-1-羧酸（抗3-[(18)F]FACBC）摄取对原发性前列腺癌进行表征。
Am J Nucl Med Mol Imaging. 2013;3(1):85-96. Epub 2013 Jan 5.
9
(4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies.使用 PET 成像肝细胞癌中 xC 转运体活性的 (4S)-4-(3-18F-氟丙基)-L-谷氨酸：临床前和探索性临床研究。
J Nucl Med. 2013 Jan;54(1):117-23. doi: 10.2967/jnumed.112.108704. Epub 2012 Dec 11.
10
Comparative evaluation of 18F-labeled glutamic acid and glutamine as tumor metabolic imaging agents.18F 标记谷氨酸和谷氨酰胺作为肿瘤代谢显像剂的比较评价。
J Nucl Med. 2012 Oct;53(10):1616-24. doi: 10.2967/jnumed.111.101279. Epub 2012 Aug 30.