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Abstract High grade serous ovarian cancer displays two metabolic subtypes; a high OXPHOS subtype that shows increased expression of genes encoding electron transport chain components, increased oxygen consumption, and increased chemosensitivity, and a low OXPHOS subtype that exhibits glycolytic metabolism and is more drug resistant. We show here in patient-derived organoids and in the xenografts obtained by their subcutaneous implantation that the low OXPHOS subtype shows higher lactate dehydrogenase activity and monocarboxylate transporter 4 expression than the high OXPHOS subtype and increased lactate labeling in 13 C magnetic resonance spectroscopy (MRS) measurements of hyperpolarized 1- 13 Cpyruvate metabolism. There was no difference between the subtypes in PET measurements of 2-deoxy-2-fluorine-18fluoro-D-glucose ( 18 FFDG) uptake. Both metabolic imaging techniques could detect the early response to Carboplatin treatment in drug-sensitive high OXPHOS xenografts and no response in drug-resistant in low OXPHOS xenografts. 13 C magnetic resonance spectroscopic imaging of hyperpolarized 1- 13 Cpyruvate metabolism has the potential to be used clinically to distinguish low OXPHOS and high OXPHOS tumor deposits in HGSOC patients and to detect their differential responses to treatment.
Chia et al. (Fri,) studied this question.