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2-[F]FDG放射性代谢物的指纹图谱——2-[F]FDG-6-P之外的组织特异性代谢如何影响示踪剂积累。

A fingerprint of 2-[F]FDG radiometabolites - How tissue-specific metabolism beyond 2-[F]FDG-6-P could affect tracer accumulation.

作者信息

Patronas Eva-Maria, Balber Theresa, Miller Anne, Geist Barbara Katharina, Michligk Antje, Vraka Chrysoula, Krisch Maximilian, Rohr-Udilova Nataliya, Haschemi Arvand, Viernstein Helmut, Hacker Marcus, Mitterhauser Markus

机构信息

Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna 1090, Austria.

Division of Pharmaceutical Technology and Biopharmaceutics, Department of Pharmaceutical Sciences, University of Vienna, Vienna 1090, Austria.

出版信息

iScience. 2023 Oct 6;26(11):108137. doi: 10.1016/j.isci.2023.108137. eCollection 2023 Nov 17.

DOI:10.1016/j.isci.2023.108137
PMID:37867937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10585399/
Abstract

Studies indicate that the radiotracer 2-[F]fluoro-2-deoxy-D-glucose (2-[F]FDG) can be metabolized beyond 2-[F]FDG-6-phosphate (2-[F]FDG-6-P), but its metabolism is incompletely understood. Most importantly, it remains unclear whether downstream metabolism affects tracer accumulation Here we present a fingerprint of 2-[F]FDG radiometabolites over time in cancer cells, corresponding tumor xenografts and murine organs. Strikingly, radiometabolites representing glycogen metabolism or the oxPPP correlated inversely with tracer accumulation across all examined tissues. Recent studies suggest that not only hexokinase, but also hexose-6-phosphate dehydrogenase (H6PD), an enzyme of the oxidative pentose phosphate pathway (oxPPP), determines 2-[F]FDG accumulation. However, little is known about the corresponding enzyme glucose-6-phosphate dehydrogenase (G6PD). Our mechanistic experiments on the role of the oxPPP propose that 2-[F]FDG can be metabolized via both G6PD and H6PD, but data from separate enzyme knockdown suggest diverging roles in downstream tracer metabolism. Overall, we propose that tissue-specific metabolism beyond 2-[F]FDG-6-P could matter for imaging.

摘要

研究表明，放射性示踪剂2-[F]氟-2-脱氧-D-葡萄糖（2-[F]FDG）可以代谢生成2-[F]FDG-6-磷酸（2-[F]FDG-6-P）以上的产物，但其代谢过程尚未完全清楚。最重要的是，尚不清楚下游代谢是否会影响示踪剂的蓄积。在此，我们展示了癌细胞、相应肿瘤异种移植模型和小鼠器官中2-[F]FDG放射性代谢产物随时间变化的图谱。引人注目的是，代表糖原代谢或磷酸戊糖途径（oxPPP）的放射性代谢产物与所有检测组织中的示踪剂蓄积呈负相关。最近的研究表明，不仅己糖激酶，而且氧化磷酸戊糖途径（oxPPP）中的一种酶——6-磷酸己糖脱氢酶（H6PD），也决定了2-[F]FDG的蓄积。然而，对于相应的酶葡萄糖-6-磷酸脱氢酶（G6PD）却知之甚少。我们关于oxPPP作用的机制实验表明，2-[F]FDG可以通过G6PD和H6PD进行代谢，但来自单独酶敲低实验的数据表明它们在下游示踪剂代谢中的作用不同。总体而言，我们认为2-[F]FDG-6-P以上的组织特异性代谢可能对成像很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/fe4abdedc139/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/550db1f0ad36/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/1ad878ebe3a7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/e438066c24c0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/bde30955ddb5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/2806efc2df76/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/fa1378d04ef7/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/23a5bd53b40f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/fe4abdedc139/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/550db1f0ad36/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/1ad878ebe3a7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/e438066c24c0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/bde30955ddb5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/2806efc2df76/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/fa1378d04ef7/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/23a5bd53b40f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/10585399/fe4abdedc139/gr7.jpg

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