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本文引用的文献

1
Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study.临床前TSPO配体PET用于可视化人胶质瘤异种移植瘤：一项初步研究。
PLoS One. 2015 Oct 30;10(10):e0141659. doi: 10.1371/journal.pone.0141659. eCollection 2015.
2
Facile synthesis of SSR180575 and discovery of 7-chloro-N,N,5-trimethyl-4-oxo-3(6-[(18)F]fluoropyridin-2-yl)-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, a potent pyridazinoindole ligand for PET imaging of TSPO in cancer.SSR180575的简便合成及7-氯-N,N,5-三甲基-4-氧代-3(6-[(18)F]氟吡啶-2-基)-3,5-二氢-4H-哒嗪并[4,5-b]吲哚-1-乙酰胺的发现，一种用于癌症中TSPO的PET成像的有效哒嗪并吲哚配体。
Bioorg Med Chem Lett. 2014 Sep 15;24(18):4466-4471. doi: 10.1016/j.bmcl.2014.07.091. Epub 2014 Aug 8.
3
Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma.新型TSPO-PET配体2-(5,7-二乙基-2-(4-(2-[(18)F]氟乙氧基)苯基)吡唑并[1,5-a]嘧啶-3-基)-N,N-二乙酰胺([(18)F]VUIIS1008)在胶质瘤中的临床前影像学评估
Mol Imaging Biol. 2014 Dec;16(6):813-20. doi: 10.1007/s11307-014-0743-2.
4
Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.线粒体转位蛋白与诊断配体复合物的结构。
Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725.
5
Synthesis and structure-activity relationships of 5,6,7-substituted pyrazolopyrimidines: discovery of a novel TSPO PET ligand for cancer imaging.5,6,7-取代吡唑并嘧啶的合成及构效关系：一种新型 TSPO PET 配体用于癌症成像的发现。
J Med Chem. 2013 Apr 25;56(8):3429-33. doi: 10.1021/jm4001874. Epub 2013 Apr 3.
6
Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC.原氨酸和谷氨酰胺代谢的重编程有助于致癌转录因子 c-MYC 调控的增殖和代谢反应。
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8983-8. doi: 10.1073/pnas.1203244109. Epub 2012 May 21.
7
Quantitative preclinical imaging of TSPO expression in glioma using N,N-diethyl-2-(2-(4-(2-18F-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide.使用 N,N-二乙基-2-(2-(4-(2-18F-氟乙氧基)苯基)-5,7-二甲基吡唑并[1,5-a]嘧啶-3-基)乙酰胺对胶质瘤中 TSPO 表达的定量临床前成像。
J Nucl Med. 2012 Feb;53(2):287-94. doi: 10.2967/jnumed.111.095653. Epub 2012 Jan 17.
8
Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth.致癌性 K-Ras 将葡萄糖和谷氨酰胺代谢解偶联，以支持癌细胞生长。
Mol Syst Biol. 2011 Aug 16;7:523. doi: 10.1038/msb.2011.56.
9
Development and validation of a higher-throughput equilibrium dialysis assay for plasma protein binding.用于血浆蛋白结合的高通量平衡透析测定法的开发与验证。
J Lab Autom. 2011 Feb;16(1):56-67. doi: 10.1016/j.jala.2010.06.002. Epub 2011 Jan 12.
10
Quantitative, preclinical PET of translocator protein expression in glioma using 18F-N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline.使用 18F-N-氟乙酰基-N-(2,5-二甲氧基苄基)-2-苯氧基苯胺对胶质瘤中转位蛋白表达进行定量、临床前 PET 研究。
J Nucl Med. 2011 Jan;52(1):107-14. doi: 10.2967/jnumed.110.081703. Epub 2010 Dec 13.

TSPO正电子发射断层显像（PET）配体[F]VUIIS1009A和[F]VUIIS1009B的评估：用于癌症成像的示踪剂

Evaluation of TSPO PET Ligands [F]VUIIS1009A and [F]VUIIS1009B: Tracers for Cancer Imaging.

作者信息

Tang Dewei, Li Jun, Buck Jason R, Tantawy Mohamed Noor, Xia Yan, Harp Joel M, Nickels Michael L, Meiler Jens, Manning H Charles

机构信息

Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.

出版信息

Mol Imaging Biol. 2017 Aug;19(4):578-588. doi: 10.1007/s11307-016-1027-9.

DOI:10.1007/s11307-016-1027-9
PMID:27853987
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5634614/
Abstract

PURPOSE

Positron emission tomography (PET) ligands targeting translocator protein (TSPO) are potential imaging diagnostics of cancer. In this study, we report two novel, high-affinity TSPO PET ligands that are 5,7 regioisomers, [F]VUIIS1009A ([F]3A) and [F]VUIIS1009B ([F]3B), and their initial in vitro and in vivo evaluation in healthy mice and glioma-bearing rats.

PROCEDURES

VUIIS1009A/B was synthesized and confirmed by X-ray crystallography. Interactions between TSPO binding pocket and novel ligands were evaluated and compared with contemporary TSPO ligands using 2D H-N heteronuclear single quantum coherence (HSQC) spectroscopy. In vivo biodistribution of [F]VUIIS1009A and [F]VUIIS1009B was carried out in healthy mice with and without radioligand displacement. Dynamic PET imaging data were acquired simultaneously with [F]VUIIS1009A/B injections in glioma-bearing rats, with binding reversibility and specificity evaluated by radioligand displacement. In vivo radiometabolite analysis was performed using radio-TLC, and quantitative analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.

RESULTS

Both VUIIS1009A (3A) and VUIIS1009B (3B) were found to exhibit exceptional binding affinity to TSPO, with observed IC values against PK11195 approximately 500-fold lower than DPA-714. However, HSQC NMR suggested that VUIIS1009A and VUIIS1009B share a common binding pocket within mammalian TSPO (mTSPO) as DPA-714 and to a lesser extent, PK11195. [F]VUIIS1009A ([F]3A) and [F]VUIIS1009B ([F]3B) exhibited similar biodistribution in healthy mice. In rats bearing C6 gliomas, both [F]VUIIS1009A and [F]VUIIS1009B exhibited greater binding potential (k /k )in tumor tissue compared to [F]DPA-714. Interestingly, [F]VUIIS1009B exhibited significantly greater tumor uptake (V ) than [F]VUIIS1009A, which was attributed primarily to greater plasma-to-tumor extraction efficiency.

CONCLUSIONS

The novel PET ligand [F]VUIIS1009B exhibits promising characteristics for imaging glioma; its superiority over [F]VUIIS1009A, a regioisomer, appears to be primarily due to improved plasma extraction efficiency. Continued evaluation of [F]VUIIS1009B as a high-affinity TSPO PET ligand for precision medicine appears warranted.

摘要

目的

靶向转运体蛋白（TSPO）的正电子发射断层扫描（PET）配体是癌症潜在的成像诊断剂。在本研究中，我们报告了两种新型的、高亲和力的TSPO PET配体，即5,7区域异构体[F]VUIIS1009A（[F]3A）和[F]VUIIS1009B（[F]3B），以及它们在健康小鼠和荷胶质瘤大鼠中的初步体外和体内评估。

程序

合成VUIIS1009A/B并通过X射线晶体学进行确认。使用二维H-N异核单量子相干（HSQC）光谱评估TSPO结合口袋与新型配体之间的相互作用，并与当代TSPO配体进行比较。在有或没有放射性配体置换的健康小鼠中进行[F]VUIIS1009A和[F]VUIIS1009B的体内生物分布研究。在荷胶质瘤大鼠中注射[F]VUIIS1009A/B的同时获取动态PET成像数据，通过放射性配体置换评估结合的可逆性和特异性。使用放射性薄层色谱法进行体内放射性代谢物分析，并使用代谢物校正的动脉输入函数对PET数据进行定量分析。通过组织学和免疫组织化学对成像进行验证。

结果

发现VUIIS1009A（3A）和VUIIS1009B（3B）对TSPO均表现出卓越的结合亲和力，观察到的针对PK11195的IC值比DPA-714低约500倍。然而，HSQC核磁共振表明，VUIIS1009A和VUIIS1009B在哺乳动物TSPO（mTSPO）中与DPA-714共享一个共同的结合口袋，在较小程度上与PK11195共享。[F]VUIIS1009A（[F]3A）和[F]VUIIS1009B（[F]3B）在健康小鼠中表现出相似的生物分布。在荷C6胶质瘤的大鼠中，与[F]DPA-714相比，[F]VUIIS1009A和[F]VUIIS1009B在肿瘤组织中均表现出更高的结合潜力（k /k ）。有趣的是，[F]VUIIS1009B表现出比[F]VUIIS1009A显著更高的肿瘤摄取（V ），这主要归因于更高的血浆到肿瘤的提取效率。

结论

新型PET配体[F]VUIIS1009B在胶质瘤成像方面表现出有前景的特性；其相对于区域异构体[F]VUIIS1009A的优势似乎主要归因于血浆提取效率的提高。继续评估[F]VUIIS1009B作为用于精准医学的高亲和力TSPO PET配体似乎是有必要的。