{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/37786"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/37786","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Magnetic Resonance Imaging of a Natural Killer Cell Therapy in a Mouse Model of Prostate Cancer","abstract":"Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized 13C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for 13C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: KHYG-1 were toxic to PC-3M in vitro and were successfully labeled with MoldayRhodamine, a superparamagnetic iron oxide nanoparticle (SPIO). A subcutaneous PC-3M tumour model was used to investigate tracking of KHYG-1 in vivo using the bSSFP sequence. Four days after administration, KHYG-1 accumulation in the tumours was detected by histology but not by MRI, although labeled KHYG-1 at high density were visible in MR images. The bSSFP sequence was then optimized for imaging the mouse prostate and the whole mouse body. Tumour development in an orthotopic prostate cancer model was characterized by MRI and histology for tumour growth, metastasis and tumour metabolism. Tumours were visible by MRI day 9 after injection. Using histology, metastasis was detected in the lymph nodes and spleen of the mice. Necrotic regions in the tumours were detected on day 22 by both anatomical imaging and pyruvate spectroscopy and were confirmed by histology. Conclusions: KHYG-1 cell therapy shows promise as a treatment of prostate cancer. A mouse model that developed lymph node metastases was characterized. Based on the accumulation of KHYG-1 in SC tumours 4 days after administration, and the consistent presence of MRI-visible tumours on day 9-13, a treatment time point of 9-13 days is proposed for future NK cell tracking experiments.","abstract_html":"Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized 13C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for 13C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: KHYG-1 were toxic to PC-3M in vitro and were successfully labeled with MoldayRhodamine, a superparamagnetic iron oxide nanoparticle (SPIO). A subcutaneous PC-3M tumour model was used to investigate tracking of KHYG-1 in vivo using the bSSFP sequence. Four days after administration, KHYG-1 accumulation in the tumours was detected by histology but not by MRI, although labeled KHYG-1 at high density were visible in MR images. The bSSFP sequence was then optimized for imaging the mouse prostate and the whole mouse body. Tumour development in an orthotopic prostate cancer model was characterized by MRI and histology for tumour growth, metastasis and tumour metabolism. Tumours were visible by MRI day 9 after injection. Using histology, metastasis was detected in the lymph nodes and spleen of the mice. Necrotic regions in the tumours were detected on day 22 by both anatomical imaging and pyruvate spectroscopy and were confirmed by histology. Conclusions: KHYG-1 cell therapy shows promise as a treatment of prostate cancer. A mouse model that developed lymph node metastases was characterized. Based on the accumulation of KHYG-1 in SC tumours 4 days after administration, and the consistent presence of MRI-visible tumours on day 9-13, a treatment time point of 9-13 days is proposed for future NK cell tracking experiments.","abstract_has_math":false,"creators":["Mallett, Christiane L"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Medical Biophysics","degree_department":null,"school":null,"contributors":[],"advisors":["Paula Foster"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-04-19","date_published":"2013-04-19","updated_at":"2026-07-27T21:55:58Z","subjects":["Natural killer cells","prostate cancer","PC-3M","cell tracking","hyperpolarized carbon 13 spectroscopy","pyruvate","nude mouse","metastasis"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/37786","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Paula Foster"]},{"key":"dc:creator","label":"Author","values":["Mallett, Christiane L"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T21:42:01Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T21:42:01Z"]},{"key":"dc:date.issued","label":"Date","values":["2013-04-19"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medical Biophysics"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph D"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Natural killer cells","prostate cancer","PC-3M","cell tracking","hyperpolarized carbon 13 spectroscopy","pyruvate","nude mouse","metastasis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/37786"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized 13C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for 13C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: KHYG-1 were toxic to PC-3M in vitro and were successfully labeled with MoldayRhodamine, a superparamagnetic iron oxide nanoparticle (SPIO). A subcutaneous PC-3M tumour model was used to investigate tracking of KHYG-1 in vivo using the bSSFP sequence. Four days after administration, KHYG-1 accumulation in the tumours was detected by histology but not by MRI, although labeled KHYG-1 at high density were visible in MR images. The bSSFP sequence was then optimized for imaging the mouse prostate and the whole mouse body. Tumour development in an orthotopic prostate cancer model was characterized by MRI and histology for tumour growth, metastasis and tumour metabolism. Tumours were visible by MRI day 9 after injection. Using histology, metastasis was detected in the lymph nodes and spleen of the mice. Necrotic regions in the tumours were detected on day 22 by both anatomical imaging and pyruvate spectroscopy and were confirmed by histology. Conclusions: KHYG-1 cell therapy shows promise as a treatment of prostate cancer. A mouse model that developed lymph node metastases was characterized. Based on the accumulation of KHYG-1 in SC tumours 4 days after administration, and the consistent presence of MRI-visible tumours on day 9-13, a treatment time point of 9-13 days is proposed for future NK cell tracking experiments."]},{"key":"dc:title","label":"Title","values":["Magnetic Resonance Imaging of a Natural Killer Cell Therapy in a Mouse Model of Prostate Cancer"]}]}],"canonical_facts":{"dc:contributor.advisor":["Paula Foster"],"dc:creator":["Mallett, Christiane L"],"dc:date.accessioned":["2025-07-10T21:42:01Z"],"dc:date.available":["2025-07-10T21:42:01Z"],"dc:date.issued":["2013-04-19"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Purpose: This thesis uses magnetic resonance imaging (MRI) techniques to study natural killer (NK) cell therapy in a nude mouse model of prostate cancer. Cellular MRI, anatomical MRI and hyperpolarized 13C spectroscopy were used to study various aspects of the model. Methods: The cells used were KHYG-1 NK cells and PC-3M prostate cancer cells. Imaging was performed on a clinical 3T GE MR 750 scanner, using a high-performance gradient insert for acquisition with the balanced steady state free precession (bSSFP) sequence, and using the built-in gradients for 13C pyruvate spectroscopy. Pyruvate was hyperpolarized by dynamic nuclear polarization. Results: KHYG-1 were toxic to PC-3M in vitro and were successfully labeled with MoldayRhodamine, a superparamagnetic iron oxide nanoparticle (SPIO). A subcutaneous PC-3M tumour model was used to investigate tracking of KHYG-1 in vivo using the bSSFP sequence. Four days after administration, KHYG-1 accumulation in the tumours was detected by histology but not by MRI, although labeled KHYG-1 at high density were visible in MR images. The bSSFP sequence was then optimized for imaging the mouse prostate and the whole mouse body. Tumour development in an orthotopic prostate cancer model was characterized by MRI and histology for tumour growth, metastasis and tumour metabolism. Tumours were visible by MRI day 9 after injection. Using histology, metastasis was detected in the lymph nodes and spleen of the mice. Necrotic regions in the tumours were detected on day 22 by both anatomical imaging and pyruvate spectroscopy and were confirmed by histology. Conclusions: KHYG-1 cell therapy shows promise as a treatment of prostate cancer. A mouse model that developed lymph node metastases was characterized. Based on the accumulation of KHYG-1 in SC tumours 4 days after administration, and the consistent presence of MRI-visible tumours on day 9-13, a treatment time point of 9-13 days is proposed for future NK cell tracking experiments."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/37786"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Natural killer cells","prostate cancer","PC-3M","cell tracking","hyperpolarized carbon 13 spectroscopy","pyruvate","nude mouse","metastasis"],"dc:title":["Magnetic Resonance Imaging of a Natural Killer Cell Therapy in a Mouse Model of Prostate Cancer"],"dc:type":["thesis"],"thesis:degree_discipline":["Medical Biophysics"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:55:58Z"}