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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Thursday, February 20, 2025
A type of metabolic imaging using carbon-13 (13C) magnetic resonance spectroscopy may distinguish between high–oxidative phosphorylation (OXPHOS) and low-OXPHOS subtypes of high-grade serous ovarian cancer, according to a recent study in xenografts. Previously, the high-OXPHOS subtype has been shown to be more chemosensitive, and the low-OXPHOS subtype, more drug-resistant. The research was conducted by Kevin M. Brindle, PhD, of the University of Cambridge, United Kingdom, and published in Oncogene.
“Imaging of hyperpolarized [1-13C] pyruvate metabolism has the potential to be used clinically to distinguish low-OXPHOS and high-OXPHOS tumor deposits in high-grade serous ovarian cancer patients and to detect their differential responses to treatment,” the investigators commented.
The researchers grew organoids derived from ascites from patients with stage 3 or 4 high-grade serous ovarian cancer. Then they created xenografts by subcutaneously implanting some of the organoids in immunocompromised female mice and analyzing the resulting tumors. They performed two types of metabolic imaging on tumor extracts: 13C magnetic resonance spectroscopy measurements of hyperpolarized [1-13C] pyruvate metabolism, and PET measurements of [18F] FDG uptake.
The PET measurements could not distinguish the low-OXPHOS from the high-OXPHOS subtype, but the 13C magnetic resonance spectroscopy of pyruvate metabolism could. In the latter type of imaging, the low-OXPHOS subtype had higher lactate dehydrogenase activity, monocarboxylate transporter 4 expression, and lactate labeling than the high-OXPHOS subtype.
High-OXPHOS xenografts have previously been shown to be sensitive to carboplatin treatment, whereas low-OXPHOS xenografts have been shown to be resistant to such treatment. When the researchers treated xenografts with carboplatin, both metabolic imaging techniques could detect the difference in responses between subtypes before any change in tumor volume—PET as early as 1 week after the start of treatment and 13C magnetic resonance spectroscopy after 3 weeks.
Disclosure: The study authors reported no conflicts of interest.
