Metabolic imaging detects low levels of glycolytic activity that vary with levels of c-Myc expression in patient-derived xenograft models of glioblastoma.

Richard Mair, Alan Wright, Susana Ros, De-en Hu, Thomas Calvert Booth, Felix Kreis, Jyotsna Rao, Colin Watts, Kevin Brindle

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29 Citations (Scopus)
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Abstract

13C MRI of hyperpolarized [1-13C]pyruvate metabolism has been used in oncology to detect disease, investigate disease progression, and monitor response to treatment with a view to guiding treatment in individual patients. This technique has translated to the clinic with initial studies in prostate cancer. Here, we use the technique to investigate its potential uses in patients with glioblastoma (GB). We assessed the metabolism of hyperpolarized [1-13C]pyruvate in an orthotopically implanted cell line model (U87) of GB and in patient-derived tumors, where these were produced by orthotopic implantation of cells derived from different patients. Lactate labeling was higher in the U87 tumor when compared with patient-derived tumors, which displayed intertumoral heterogeneity, reflecting the intra- and inter- tumoral heterogeneity in the patients' tumors from which they were derived. Labeling in some patient-derived tumors could be observed before their appearance in morphologic images, whereas in other tumors it was not significantly
greater than the surrounding brain. Increased lactate labeling in tumors correlated with c-Myc–driven expression of hexo- kinase 2, lactate dehydrogenase A, and the monocarboxylate transporters and was accompanied by increased radioresis- tance. Because c-Myc expression correlates with glioma grade, this study demonstrates that imaging with hyperpo- larized [1-13C]pyruvate could be used clinically with patients with GB to determine disease prognosis, to detect early responses to drugs that modulate c-Myc expression, and to select tumors, and regions of tumors for increased radio- therapy dose.
Significance: Metabolic imaging with hyperpolarized [1-13C]pyruvate detects low levels of c-Myc–driven glyco- lysis in patient-derived glioblastoma models, which, when translated to the clinic, could be used to detect occult disease, determine disease prognosis, and target radiotherapy.
Original languageEnglish
Pages (from-to)5408–18
Number of pages11
JournalCancer Research
Volume78
Issue number18
Early online date27 Jul 2018
DOIs
Publication statusPublished - Sept 2018

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