Table 1 |.
Isotope tracing studies in patients with cancer
| Study | Cancer | Tracer(s) | Key conclusions |
|---|---|---|---|
| Fan et al., 2009 (ref. 19) | NSCLC | [U-13C]glucose | Labelling of glycolytic and TCA cycle intermediates in tumours exceeds labelling in lung Labelling patterns in TCA cycle intermediates are consistent with PC |
| Maher et al., 2012 (ref. 39) | Glioma, brain metastases | [U-13C]glucose | Glycolysis, TCA cycle turnover, anaplerosis and glutamine synthesis are active in these tumours in vivo Relatively low labelling of acetyl-CoA feeding the TCA cycle, suggesting that tumours oxidize other fuels in addition to glucose |
| Mashimo et al., 2014 (ref. 43) | Glioma, brain metastases | [1,2-13C]acetate | Blood acetate provides an acetyl-CoA source for the TCA cycle in human glioblastoma and NSCLC metastases to the brain |
| Sellers et al., 2016 (ref. 27) | NSCLC | [U-13C]glucose | Tumours express high levels of PC, and labelling provides strong evidence of enhanced PC contribution to the TCA cycle in tumours relative to adjacent lung |
| Hensley et al., 2016 (ref. 36) | NSCLC | [U-13C]glucose | Treatment-naive NSCLCs display extensive metabolic heterogeneity Regional metabolic heterogeneity exists within the same tumour Some metabolic characteristics correlate with regional perfusion assessed by MRI |
| Faubert et al., 2017 (ref. 33) | NSCLC | [U-13C]glucose, [U-13C]lactate | Lactate from the blood enters lung tumours and contributes to TCA cycle metabolism |
| Courtney et al., 2018 (ref. 37) | ccRCC | [U-13C]glucose, [U-13C]acetate | The contribution of glucose to the TCA cycle is low in ccRCC relative to adjacent kidney and tumours from the lung and brain |
| Gonsalves et al., 2020 (ref. 42) | Multiple myeloma | [5-13C]glutamine, [U-13C]glutamine | The contribution of glutamine to the TCA cycle in CD138+ bone marrow cells is higher in multiple myeloma than in the premalignant lesion MGUS |
| Johnston et al., 2021 (ref. 35) | Extracranial solid tumours in children | [U-13C]glucose | Intra-operative [U-13C]glucose infusions are safe and informative in children as young as 4 months Glucose provides carbon to the TCA cycle in neuroblastoma, sarcoma and other paediatric malignancies |
| Ghergurovich et al., 2021 (ref. 38) | Triple-negative breast cancer | [1,2-13C]glucose | Isotope labelling indicates metabolism of glucose within tumours to amino acids and pentose phosphate pathway intermediates Within tumours, ribose phosphate is largely produced by the oxidative rather than non-oxidative pentose phosphate pathway |
ccRCC, clear cell renal cell carcinoma; CD138, cluster of differentiation 138 (also known as syndecan-1); MGUS, monoclonal gammopathy of undetermined significance; NSCLC, non-small-cell lung cancer; PC, pyruvate carboxylase; TCA, tricarboxylic acid.