If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism
The glucose derivative 2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose (2-[<sup>18</sup>F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[<sup>18</sup>F]FDG is said to be t...
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doaj-38776b11852949319fc0a080de4afbbd2021-09-26T00:55:45ZengMDPI AGPharmaceuticals1424-82472021-09-011491091010.3390/ph14090910If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG MetabolismEva-Maria Klebermass0Mahshid Mahmudi1Barbara Katharina Geist2Verena Pichler3Chrysoula Vraka4Theresa Balber5Anne Miller6Arvand Haschemi7Helmut Viernstein8Nataliya Rohr-Udilova9Marcus Hacker10Markus Mitterhauser11Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDivision of Pharmaceutical Chemistry, Department of Pharmaceutical Sciences, University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, AustriaDivision of Pharmaceutical Technology and Biopharmaceutics, Department of Pharmaceutical Sciences, University of Vienna, 1090 Vienna, AustriaDivision of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaDivision of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, AustriaThe glucose derivative 2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose (2-[<sup>18</sup>F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[<sup>18</sup>F]FDG is said to be trapped intracellularly as 2-[<sup>18</sup>F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[<sup>18</sup>F]FDG-6-phosphate and even postulating 2-[<sup>18</sup>F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[<sup>18</sup>F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[<sup>18</sup>F]FDG metabolism with intracellular tracer accumulation, efflux and the cells’ metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[<sup>18</sup>F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[<sup>18</sup>F]FDG-6-phosphate were 2-[<sup>18</sup>F]FDMannose-6-phosphate, 2-[<sup>18</sup>F]FDG-1,6-bisphosphate and 2-[<sup>18</sup>F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells’ metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[<sup>18</sup>F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[<sup>18</sup>F]FDG metabolism might help to improve cancer research and tumor diagnosis.https://www.mdpi.com/1424-8247/14/9/9102-[<sup>18</sup>F]FDG2-[<sup>18</sup>F]FDG metabolismPET-tracer metabolismmolecular imagingcancer metabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eva-Maria Klebermass Mahshid Mahmudi Barbara Katharina Geist Verena Pichler Chrysoula Vraka Theresa Balber Anne Miller Arvand Haschemi Helmut Viernstein Nataliya Rohr-Udilova Marcus Hacker Markus Mitterhauser |
spellingShingle |
Eva-Maria Klebermass Mahshid Mahmudi Barbara Katharina Geist Verena Pichler Chrysoula Vraka Theresa Balber Anne Miller Arvand Haschemi Helmut Viernstein Nataliya Rohr-Udilova Marcus Hacker Markus Mitterhauser If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism Pharmaceuticals 2-[<sup>18</sup>F]FDG 2-[<sup>18</sup>F]FDG metabolism PET-tracer metabolism molecular imaging cancer metabolism |
author_facet |
Eva-Maria Klebermass Mahshid Mahmudi Barbara Katharina Geist Verena Pichler Chrysoula Vraka Theresa Balber Anne Miller Arvand Haschemi Helmut Viernstein Nataliya Rohr-Udilova Marcus Hacker Markus Mitterhauser |
author_sort |
Eva-Maria Klebermass |
title |
If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism |
title_short |
If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism |
title_full |
If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism |
title_fullStr |
If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism |
title_full_unstemmed |
If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[<sup>18</sup>F]FDG Metabolism |
title_sort |
if it works, don’t touch it? a cell-based approach to studying 2-[<sup>18</sup>f]fdg metabolism |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2021-09-01 |
description |
The glucose derivative 2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose (2-[<sup>18</sup>F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[<sup>18</sup>F]FDG is said to be trapped intracellularly as 2-[<sup>18</sup>F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[<sup>18</sup>F]FDG-6-phosphate and even postulating 2-[<sup>18</sup>F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[<sup>18</sup>F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[<sup>18</sup>F]FDG metabolism with intracellular tracer accumulation, efflux and the cells’ metabolic state and used a graphical Gaussian model to visualize metabolic patterns. The extent of 2-[<sup>18</sup>F]FDG metabolism varied considerably, dependent on the cell line, and was significantly enhanced by glucose withdrawal. However, the metabolic pattern was quite conserved. The most important radiometabolites beyond 2-[<sup>18</sup>F]FDG-6-phosphate were 2-[<sup>18</sup>F]FDMannose-6-phosphate, 2-[<sup>18</sup>F]FDG-1,6-bisphosphate and 2-[<sup>18</sup>F]FD-phosphogluconolactone. Enhanced radiometabolite formation under glucose reduction was accompanied by reduced efflux and mirrored the cells’ metabolic switch as assessed via extracellular lactate levels. We conclude that there can be considerable metabolism beyond 2-[<sup>18</sup>F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[<sup>18</sup>F]FDG metabolism might help to improve cancer research and tumor diagnosis. |
topic |
2-[<sup>18</sup>F]FDG 2-[<sup>18</sup>F]FDG metabolism PET-tracer metabolism molecular imaging cancer metabolism |
url |
https://www.mdpi.com/1424-8247/14/9/910 |
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