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Imaging Metabolic Signatures in High Grade Serous Ovarian Cancer



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Chia, Ming Li 


High Grade Serous Ovarian Cancer (HGSOC) can be classified by gene copy number signatures into 7 subtypes that have differing prognoses and treatment sensitivities and that show differences in the activities of various signalling pathways. An ongoing clinical study has demonstrated the feasibility of imaging hyperpolarized 13C pyruvate metabolism in ovarian cancer and has demonstrated inter and intra-tumoural metabolic heterogeneity, where metabolic differences were observed between patients and between different tumour deposits within the same patient. Here I compared the use of 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized [1-13C]pyruvate metabolism and positron emission tomography (PET) measurements of 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) uptake for detecting metabolic heterogeneity between HGSOC patient-derived xenografts (PDXs) that had different copy number signatures.

I showed that differences in glycolytic metabolism between the subtypes, as defined by their copy number signatures, could be detected using hyperpolarized [1-13C]pyruvate but not with [18F]FDG PET. Dynamic Contrast Enhanced MRI measurements showed that the metabolic differences between the subtypes were not due to differences in tumour perfusion. I also investigated whether differences in tumour metabolism could help to predict and detect early treatment response. I compared the use of metabolic imaging techniques (hyperpolarized [1-13C]pyruvate imaging, [18F]FDG PET/CT) with cell death imaging techniques (diffusion-weighted 1H MRI (DWI) and 2H MRSI measurements of [2,3-2H2]fumarate metabolism, measurement of circulating tumour DNA (ctDNA)) to detect early evidence of response to standard-of-care chemotherapy (Carboplatin). Both hyperpolarized [1-13C]pyruvate and [18F]FDG-PET detected response to treatment with Carboplatin, in a Carboplatin-sensitive tumour, before there was a change in tumour volume. Both metabolic imaging techniques were successful in discriminating responding from non-responding tumours. The techniques for detecting cell death were not as sensitive for detecting treatment response, which may reflect a slow accumulation of dead cells post treatment, a lack of knowledge of when the rate of cell death increases post treatment and also because of immune clearance of dead cells. These studies have shown that imaging with hyperpolarized [1-13C]pyruvate has the potential to be used in the clinic to detect the early response of HGSOC patients to treatment.

Finally, I explored the potential of imaging glyoxalase-1 (Glo-1) activity with [2-13C]Methylglyoxal for detecting metabolic heterogeneity between breast and ovarian cancer PDXs. However, Glo-1 activity did not differ between ovarian or breast cancer subtypes and therefore while 13C MRSI with [2-13C]Methylglyoxal has the potential to detect the presence of disease it may not be useful for differentiating between different HGSOC or breast cancer subtypes.





Brindle, Kevin


high grade serous ovarian cancer, Hyperpolarized pyruvate, Metabolic imaging


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Cancer Research UK (S_4111)
CRUK Studentship (S_4111) CRUK Core funding