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.
","abstract_html":"<p>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 <sup>13</sup>C 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 <sup>13</sup>C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized [1-<sup>13</sup>C]pyruvate metabolism and positron emission tomography (PET) measurements of 2-Deoxy-2-[<sup>18</sup>F]fluoroglucose ([<sup>18</sup>F]FDG) uptake for detecting metabolic heterogeneity between HGSOC patient-derived xenografts (PDXs) that had different copy number signatures.</p> <p>I showed that differences in glycolytic metabolism between the subtypes, as defined by their copy number signatures, could be detected using hyperpolarized [1-<sup>13</sup>C]pyruvate but not with [<sup>18</sup>F]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-<sup>13</sup>C]pyruvate imaging, [<sup>18</sup>F]FDG PET/CT) with cell death imaging techniques (diffusion-weighted <sup>1</sup>H MRI (DWI) and <sup>2</sup>H MRSI measurements of [2,3-<sup>2</sup>H<sub>2</sub>]fumarate metabolism, measurement of circulating tumour DNA (ctDNA)) to detect early evidence of response to standard-of-care chemotherapy (Carboplatin). Both hyperpolarized [1-<sup>13</sup>C]pyruvate and [<sup>18</sup>F]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-<sup>13</sup>C]pyruvate has the potential to be used in the clinic to detect the early response of HGSOC patients to treatment.</p> <p>Finally, I explored the potential of imaging glyoxalase-1 (Glo-1) activity with [2-<sup>13</sup>C]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 <sup>13</sup>C MRSI with [2-<sup>13</sup>C]Methylglyoxal has the potential to detect the presence of disease it may not be useful for differentiating between different HGSOC or breast cancer subtypes.</p>","abstract_has_math":false,"creators":["Chia, Ming Li"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Brindle, Kevin"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-12-01","date_published":"2023-12-01","updated_at":"2026-07-22T22:24:18Z","subjects":["high grade serous ovarian cancer","Hyperpolarized pyruvate","Metabolic imaging"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/f9e49c24-c578-4d6b-afcd-5d9d22eeba59/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.105465","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Brindle, Kevin"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["CRUK Studentship (S_4111) CRUK Core funding"]},{"key":"dc:creator","label":"Author","values":["Chia, Ming Li"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2023-12-01"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/363358"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["high grade serous ovarian cancer","Hyperpolarized pyruvate","Metabolic imaging"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/f9e49c24-c578-4d6b-afcd-5d9d22eeba59/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.17863/CAM.105465"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d458cca7-d8f9-41b4-a61f-1511bba1fd29/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["3873ce219f13fe4e636950f35eab1313","87eda9de84448d1f82354d60eee3eb5f"]},{"key":"dc:title","label":"Title","values":["Imaging Metabolic Signatures in High Grade Serous Ovarian Cancer"]}]}],"canonical_facts":{"dc:contributor.advisor":["Brindle, Kevin"],"dc:contributor.sponsor":["CRUK Studentship (S_4111) CRUK Core funding"],"dc:creator":["Chia, Ming Li"],"dc:date.issued":["2023-12-01"],"dc:description.abstract":["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.
"],"dc:format.checksum.md5":["3873ce219f13fe4e636950f35eab1313","87eda9de84448d1f82354d60eee3eb5f"],"dc:identifier.doi":["https://doi.org/10.17863/CAM.105465"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d458cca7-d8f9-41b4-a61f-1511bba1fd29/download"],"dc:language":["eng"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/363358"],"dc:rights":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/f9e49c24-c578-4d6b-afcd-5d9d22eeba59/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"dc:subject":["high grade serous ovarian cancer","Hyperpolarized pyruvate","Metabolic imaging"],"dc:title":["Imaging Metabolic Signatures in High Grade Serous Ovarian Cancer"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:18Z"}