• 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

KRAS 基因突变检测用 (2,4)-4-[F]FGln 进行无创性 PDAC 诊断。

KRAS Mutation Detection with (2,4)-4-[F]FGln for Noninvasive PDAC Diagnosis.

机构信息

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.

出版信息

Mol Pharm. 2024 Apr 1;21(4):2034-2042. doi: 10.1021/acs.molpharmaceut.4c00082. Epub 2024 Mar 8.

DOI:10.1021/acs.molpharmaceut.4c00082
PMID:38456403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10989612/
Abstract

Pancreatic ductal adenocarcinoma (PDAC), which has a poor prognosis and nonspecific symptoms and progresses rapidly, is the most common pancreatic cancer type. Inhibitors targeting KRAS G12D and G12C mutations have been pivotal in PDAC treatment. Cancer cells with different KRAS mutations exhibit various degrees of glutamine dependency; in particular, cells with KRAS G12D mutations exhibit increased glutamine uptake. (2,4)-4-[F]FGln has recently been developed for clinical cancer diagnosis and tumor cell metabolism analysis. Thus, we verified the heterogeneity of glutamine dependency in PDAC models with different KRAS mutations by a visual and noninvasive method with (2,4)-4-[F]FGln. Two tumor-bearing mouse models (bearing the KRAS G12D or G12C mutation) were injected with (2,4)-4-[F]FGln, and positron emission tomography (PET) imaging features and biodistribution were observed and analyzed. The SUV in the regions of interest (ROI) was significantly higher in PANC-1 (G12D) tumors than in MIA PaCa-2 (G12C) tumors. Biodistribution analysis revealed higher tumor accumulation of (2,4)-4-[F]FGln and other metrics, such as T/M and T/B, in the PANC-1 mouse models compared to those in the MIAPaCa-2 mouse models. In conclusion, PDAC cells with the KRAS G12D and G12C mutations exhibit various degrees of (2,4)-4-[F]FGln uptake, indicating that (2,4)-4-[F]FGln might be applied to detect KRAS G12C and G12D mutations and provide treatment guidance.

摘要

胰腺导管腺癌（PDAC）预后差，症状不特异，进展迅速，是最常见的胰腺癌类型。针对 KRAS G12D 和 G12C 突变的抑制剂在 PDAC 治疗中至关重要。具有不同 KRAS 突变的癌细胞表现出不同程度的谷氨酰胺依赖性；特别是，具有 KRAS G12D 突变的细胞表现出增加的谷氨酰胺摄取。（2,4）-4-[F]FGln 最近已被开发用于临床癌症诊断和肿瘤细胞代谢分析。因此，我们通过使用（2,4）-4-[F]FGln 以可视化和非侵入性的方法验证了具有不同 KRAS 突变的 PDAC 模型中谷氨酰胺依赖性的异质性。将（2,4）-4-[F]FGln 注射到两个荷瘤小鼠模型（携带 KRAS G12D 或 G12C 突变）中，观察和分析正电子发射断层扫描（PET）成像特征和生物分布。感兴趣区域（ROI）中的 SUV 在 PANC-1（G12D）肿瘤中明显高于 MIA PaCa-2（G12C）肿瘤。生物分布分析显示，与 MIAPaCa-2 小鼠模型相比，PANC-1 小鼠模型中（2,4）-4-[F]FGln 的肿瘤积累更高，以及 T/M 和 T/B 等其他指标更高。总之，具有 KRAS G12D 和 G12C 突变的 PDAC 细胞表现出不同程度的（2,4）-4-[F]FGln 摄取，表明（2,4）-4-[F]FGln 可能用于检测 KRAS G12C 和 G12D 突变并提供治疗指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/25e781ba3088/mp4c00082_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/572d626de0e5/mp4c00082_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/544e54f84334/mp4c00082_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/a6c015a61419/mp4c00082_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/6ab1e13f28d7/mp4c00082_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/95254d40a76c/mp4c00082_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/25e781ba3088/mp4c00082_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/572d626de0e5/mp4c00082_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/544e54f84334/mp4c00082_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/a6c015a61419/mp4c00082_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/6ab1e13f28d7/mp4c00082_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/95254d40a76c/mp4c00082_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43c4/10989612/25e781ba3088/mp4c00082_0006.jpg

相似文献

1
KRAS Mutation Detection with (2,4)-4-[F]FGln for Noninvasive PDAC Diagnosis.KRAS 基因突变检测用 (2,4)-4-[F]FGln 进行无创性 PDAC 诊断。
Mol Pharm. 2024 Apr 1;21(4):2034-2042. doi: 10.1021/acs.molpharmaceut.4c00082. Epub 2024 Mar 8.
2
ADT-1004: a first-in-class, oral pan-RAS inhibitor with robust antitumor activity in preclinical models of pancreatic ductal adenocarcinoma.ADT-1004：一种一流的口服泛RAS抑制剂，在胰腺导管腺癌临床前模型中具有强大的抗肿瘤活性。
Mol Cancer. 2025 Mar 13;24(1):76. doi: 10.1186/s12943-025-02288-9.
3
Loss of heterozygosity for Kras promotes REDD1-dependent, non-canonical glutamine metabolism in pancreatic ductal adenocarcinoma.杂合性缺失促进 Kras 依赖性、非典型谷氨酰胺代谢在胰腺导管腺癌中的发生。
Biochem Biophys Res Commun. 2020 Jun 11;526(4):880-888. doi: 10.1016/j.bbrc.2020.03.137. Epub 2020 Apr 9.
4
PET/MR Imaging of a Lung Metastasis Model of Clear Cell Renal Cell Carcinoma with (2S,4R)-4-[F]Fluoroglutamine.（2S,4R）-4-[F]氟谷氨酸标记的透明细胞肾细胞癌肺转移模型的 PET/MR 成像。
Mol Imaging Biol. 2022 Dec;24(6):959-972. doi: 10.1007/s11307-022-01747-9. Epub 2022 Jun 22.
5
Comparative enzymology of (2S,4R)4-fluoroglutamine and (2S,4R)4-fluoroglutamate.（2S，4R）4-氟谷氨酸和（2S，4R）4-氟谷氨酸的比较酶学。
Comp Biochem Physiol B Biochem Mol Biol. 2012 Sep;163(1):108-20. doi: 10.1016/j.cbpb.2012.05.010. Epub 2012 May 19.
6
In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of F-(2S,4R)-4-Fluoroglutamine.体内正电子发射断层扫描（PET）检测肿瘤谷氨酰胺流量和代谢：F-(2S,4R)-4-氟谷氨酸在人体试验中的应用。
Radiology. 2018 May;287(2):667-675. doi: 10.1148/radiol.2017162610. Epub 2018 Jan 31.
7
MGST1 facilitates novel KRAS inhibitor resistance in KRAS-mutated pancreatic ductal adenocarcinoma by inhibiting ferroptosis.MGST1 通过抑制铁死亡促进 KRAS 突变型胰腺导管腺癌对新型 KRAS 抑制剂的耐药性。
Mol Med. 2024 Nov 5;30(1):199. doi: 10.1186/s10020-024-00972-y.
8
Exploiting Glutamine Consumption in Atherosclerotic Lesions by Positron Emission Tomography Tracer (2,4)-4-F-Fluoroglutamine.利用正电子发射断层扫描示踪剂（2,4）-4-F-氟谷氨酸探测动脉粥样硬化病灶中的谷氨酰胺代谢。
Front Immunol. 2022 Jan 25;13:821423. doi: 10.3389/fimmu.2022.821423. eCollection 2022.
9
First-in-Humans PET Imaging of Mutation Status in Non-Small Cell Lung and Colorectal Cancer Patients Using [F]PFPMD.使用 [F]PFPMD 对非小细胞肺癌和结直肠癌患者进行人类首例 PET 成像以检测突变状态。
J Nucl Med. 2023 Dec 1;64(12):1880-1888. doi: 10.2967/jnumed.123.265715.
10
Loss of Somatostatin Receptor Subtype 2 Promotes Growth of KRAS-Induced Pancreatic Tumors in Mice by Activating PI3K Signaling and Overexpression of CXCL16.生长抑素受体亚型 2 缺失通过激活 PI3K 信号和 CXCL16 的过表达促进小鼠 KRAS 诱导的胰腺肿瘤生长。
Gastroenterology. 2015 Jun;148(7):1452-65. doi: 10.1053/j.gastro.2015.02.009. Epub 2015 Feb 13.

引用本文的文献

1
Construction of a radiogenomics predictive model for KRAS mutation status in patients with non-small cell lung cancer.非小细胞肺癌患者KRAS突变状态的放射基因组学预测模型构建
J Thorac Dis. 2025 Jun 30;17(6):3749-3761. doi: 10.21037/jtd-2024-2003. Epub 2025 Jun 26.
2
Deuterium- and Fluorine-18-Labeled Glutaminea PET Imaging Agent with Enhanced In Vivo Stability.氘和氟-18标记的谷氨酰胺——一种具有增强体内稳定性的正电子发射断层显像剂
ACS Omega. 2025 Jul 3;10(27):29741-29753. doi: 10.1021/acsomega.5c03771. eCollection 2025 Jul 15.

本文引用的文献

1
Oncogenic context shapes the fitness landscape of tumor suppression.致癌环境塑造了肿瘤抑制的适应景观。
Nat Commun. 2023 Oct 12;14(1):6422. doi: 10.1038/s41467-023-42156-y.
2
Discovery of Potent Deuterated Compounds as Potential KRAS Inhibitors in Cancer Therapy.发现强效氘代化合物作为癌症治疗中潜在的KRAS抑制剂。
ACS Med Chem Lett. 2023 Mar 20;14(4):362-364. doi: 10.1021/acsmedchemlett.3c00075. eCollection 2023 Apr 13.
3
Exploiting Glutamine Consumption in Atherosclerotic Lesions by Positron Emission Tomography Tracer (2,4)-4-F-Fluoroglutamine.
利用正电子发射断层扫描示踪剂（2,4）-4-F-氟谷氨酸探测动脉粥样硬化病灶中的谷氨酰胺代谢。
Front Immunol. 2022 Jan 25;13:821423. doi: 10.3389/fimmu.2022.821423. eCollection 2022.
4
KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge.KRAS（G12D）可通过形成盐桥被强效抑制剂靶向。
Cell Discov. 2022 Jan 25;8(1):5. doi: 10.1038/s41421-021-00368-w.
5
Identification of MRTX1133, a Noncovalent, Potent, and Selective KRAS Inhibitor.鉴定 MRTX1133，一种非共价、有效和选择性的 KRAS 抑制剂。
J Med Chem. 2022 Feb 24;65(4):3123-3133. doi: 10.1021/acs.jmedchem.1c01688. Epub 2021 Dec 10.
6
Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancer.通过共同靶向胰腺癌中的 mTORC1/2 复合物克服 KRAS 和 MEK 抑制剂的适应性耐药性。
Cell Rep Med. 2020 Nov 17;1(8):100131. doi: 10.1016/j.xcrm.2020.100131.
7
Targeted inhibition of glutamine metabolism enhances the antitumor effect of selumetinib in KRAS-mutant NSCLC.对谷氨酰胺代谢的靶向抑制增强了司美替尼在KRAS突变型非小细胞肺癌中的抗肿瘤作用。
Transl Oncol. 2021 Jan;14(1):100920. doi: 10.1016/j.tranon.2020.100920. Epub 2020 Nov 1.
8
Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma.胰腺导管腺癌的分子改变与靶向治疗。
J Hematol Oncol. 2020 Oct 2;13(1):130. doi: 10.1186/s13045-020-00958-3.
9
KRAS Inhibition with Sotorasib in Advanced Solid Tumors.索托拉西布治疗晚期实体瘤的 KRAS 抑制作用。
N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.
10
Glutamine reliance in cell metabolism.谷氨酰胺在细胞代谢中的依赖性。
Exp Mol Med. 2020 Sep;52(9):1496-1516. doi: 10.1038/s12276-020-00504-8. Epub 2020 Sep 17.