Metabolic Imaging of Tumor Dynamics

Metabolic imaging has transformed our understanding of tumour biology by visualising the dynamic interplay between nutrient uptake, intracellular processing and tissue heterogeneity. Techniques such as positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) enable quantification of glucose consumption and trapping, while emerging methods employ hyperpolarised substrates and novel radiotracers to probe pathways including glycolysis, oxidative phosphorylation and the pentose phosphate shunt. By capturing temporal changes in tracer distribution and metabolic flux, clinicians and researchers can assess intratumoural subregions with differing proliferation rates, hypoxia levels and treatment sensitivities. This approach has proven invaluable for early response assessment, guiding adaptive therapy and uncovering metabolic vulnerabilities. Recent advances emphasise the significance of non-canonical metabolic routes—such as endoplasmic reticulum–bound pathways—influencing tracer retention and suggesting new targets for intervention. Collectively, metabolic imaging offers a non-invasive window onto the shifting phenotype of cancers in vivo, with direct implications for personalised oncology and drug development.

Research from Nature Portfolio

Recent studies have revealed an unexpected compartmentalisation of glucose metabolism within the endoplasmic reticulum of cancer cells. One foundational investigation demonstrated that hexose-6-phosphate dehydrogenase drives a distinct pentose phosphate pathway in the endoplasmic reticulum, diverting 2-[18F]FDG away from mitochondria and reshaping its accumulation pattern. Suppression of this enzyme reduced tracer uptake, depleted NADPH and impaired tumour cell viability, pointing to new imaging biomarkers and therapeutic targets. A complementary work examined the combined metabolic stress of metformin treatment and short-term starvation in experimental colon and breast tumours. Dynamic imaging of 2-[18F]FDG uptake captured additive suppression of glycolysis and oxidative phosphorylation, correlating with near-complete tumour growth inhibition. These investigations underscore how modulation of energy pathways can be monitored in real time and how emerging metabolic circuits can refine interpretation of standard imaging readouts.

Metabolic Imaging of Tumor Dynamics publication trend

The graph below shows the total number of articles in metabolic imaging of tumor dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Positron Emission Tomography (PET): A non-invasive imaging modality that detects positron-emitting radiotracers to map biochemical processes in vivo.

2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG): A radioactive glucose analogue used to measure cellular glucose uptake and phosphorylation rates.

Radiometabolite: A metabolic product of a radiotracer formed after enzymatic conversion, which can affect its distribution and imaging signal.

Pentose Phosphate Pathway (PPP): A metabolic route parallel to glycolysis that generates NADPH and ribose-5-phosphate for biosynthesis and antioxidant defence.

References

1. A fingerprint of 2-[18F]FDG radiometabolites – How tissue-specific metabolism beyond 2-[18F]FDG-6-P could affect tracer accumulation. iScience (2023).
2. Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt. Scientific Reports (2016).
3. Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer. Scientific Reports (2016).
4. If It Works, Don’t Touch It? A Cell-Based Approach to Studying 2-[18F]FDG Metabolism. Pharmaceuticals (2021).