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Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose

2013; Nature Portfolio; Volume: 20; Issue: 1 Linguagem: Inglês

10.1038/nm.3416

1546-170X

Tiago B. Rodrigues, Eva Serrão, Brett W. C. Kennedy, De‐En Hu, Mikko I. Kettunen, Kevin M. Brindle,

Atomic and Subatomic Physics Research

One of the most likely substrates for metabolic imaging of response to treatment in cancer is glucose, but until now, using hyperpolarized 13C-labelled glucose has been problematic because of the short lifetime of the hyperpolarization in this molecule. Using [U-13C, U-2H]glucose, Tiago Rodrigues et al. now show that they are able to image its glycolytic conversion to lactate in two mouse tumor models in vivo, and that in one model, flux is markedly reduced after treatment with the chemotherapeutic drug etoposide. In this study, we monitored glycolysis in mouse lymphoma and lung tumors by measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate using 13C magnetic resonance spectroscopy and spectroscopic imaging. We observed labeled lactate only in tumors and not in surrounding normal tissue or other tissues in the body and found that it was markedly decreased at 24 h after treatment with a chemotherapeutic drug. We also detected an increase in a resonance assigned to 6-phosphogluconate in the pentose phosphate pathway. This technique could provide a new way of detecting early evidence of tumor treatment response in the clinic and of monitoring tumor pentose phosphate pathway activity.