Abstract
The glucose derivative 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) is still the most used radiotracer for positron emission tomography, as it visualizes glucose utilization and energy demand. In general, 2-[18F]FDG is said to be trapped intracellularly as 2-[18F]FDG-6-phosphate, which cannot be further metabolized. However, increasingly, this dogma is being questioned because of publications showing metabolism beyond 2-[18F]FDG-6-phosphate and even postulating 2-[18F]FDG imaging to depend on the enzyme hexose-6-phosphate dehydrogenase in the endoplasmic reticulum. Therefore, we aimed to study 2-[18F]FDG metabolism in the human cancer cell lines HT1080, HT29 and Huh7 applying HPLC. We then compared 2-[18F]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-[18F]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-[18F]FDG-6-phosphate were 2-[18F]FDMannose-6-phosphate, 2-[18F]FDG-1,6-bisphosphate and 2-[18F]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-[18F]FDG-6-phosphate in cancer cell lines and a comprehensive understanding of 2-[18F]FDG metabolism might help to improve cancer research and tumor diagnosis.
Highlights
Introduction distributed under the terms andThe radioactively labelled glucose derivative 2-[18 F]fluoro-2-deoxy-D-glucose (2-[18 F]FDG) is still the most used tracer in positron emission tomography (PET) [1,2]
We found that—except for HT29—metabolism beyond 2-[18 F]FDG-6-P was not pronounced under glucose conditions
We could show that the extent of 2-[18 F]FDG metabolism is not the same in different cancer cell lines and that glucose deprivation significantly enhances radiometabolite formation and total intracellular accumulation dependent on the cell line
Summary
Introduction distributed under the terms andThe radioactively labelled glucose derivative 2-[18 F]fluoro-2-deoxy-D-glucose (2-[18 F]FDG) is still the most used tracer in positron emission tomography (PET) [1,2]. This ineffective way to generate energy causes cells to consume more glucose [3]. Higher glucose utilization might occur naturally in healthy tissues such as brain (potentially complicating diagnosis), or at sites of inflammation (causing false-positive results in cancer diagnosis) [1,2]. Because of their metabolic makeup, some cancers by nature show low 2-[18 F]FDG avidity [4], calling for more specific, receptor-based tracers
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