{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/333705"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/333705","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Development of 89Zirconium-PET Tracers for Immune Cell Imaging","abstract":"The use of cell-based therapies as a living drug have gained considerable attention for the treatment of a range of conditions such as genetic diseases, autoimmune disorders and cancer. The emergence of genetically engineered T cells expressing chimeric antigen receptors (CAR T-cells), together with modulations of immune checkpoints have brought the rapidly advancing field of immunotherapy into a new, revolutionary spotlight with a renewed interest in cell-based therapies. In vivo imaging and tracking of cells can be used to non-invasively improve the accuracy, efficacy and safety of novel immune-modulatory treatments and cell therapies. Positron Emission Tomography (PET) is a powerful non-invasive imaging technique that can be utilised for spatial and longitudinal tracking of different cell types. The long half-life PET isotope zirconium-89 (t1/2 = 78.4 h) has become increasingly available and [89Zr]Zr-Oxine has recently emerged as a promising candidate for direct cell labelling and longitudinal cell tracking. However, the water insolubility and synthesis method of [89Zr]Zr-Oxine may limit its implementation as a routine clinical imaging tool and little work has been performed looking at alternatives to this compound. The aim of this thesis was to investigate alternative approaches and methods for the direct labelling of cells using zirconium-89. This work also describes the first use of zirconium-89 in Cambridge and the set-up of the infrastructure and methods. First, the sensitivity of detecting 89Zr-labelled cells on clinical PET systems was investigated that can inform on the minimal cellular radioactivity needed for detection in prospective clinical studies. Secondly, a peptide-based approach was developed whereby cell penetrating peptides were tested for 89Zr-labelling, purification, quality control and their in vitro properties. 89Zr-labelled peptides were subsequently employed for direct cell labelling in comparison to [89Zr]Zr-Oxine in preparation for preclinical studies.","abstract_html":"The use of cell-based therapies as a living drug have gained considerable attention for the treatment of a range of conditions such as genetic diseases, autoimmune disorders and cancer. The emergence of genetically engineered T cells expressing chimeric antigen receptors (CAR T-cells), together with modulations of immune checkpoints have brought the rapidly advancing field of immunotherapy into a new, revolutionary spotlight with a renewed interest in cell-based therapies. In vivo imaging and tracking of cells can be used to non-invasively improve the accuracy, efficacy and safety of novel immune-modulatory treatments and cell therapies. Positron Emission Tomography (PET) is a powerful non-invasive imaging technique that can be utilised for spatial and longitudinal tracking of different cell types. The long half-life PET isotope zirconium-89 (t1/2 = 78.4 h) has become increasingly available and [89Zr]Zr-Oxine has recently emerged as a promising candidate for direct cell labelling and longitudinal cell tracking. However, the water insolubility and synthesis method of [89Zr]Zr-Oxine may limit its implementation as a routine clinical imaging tool and little work has been performed looking at alternatives to this compound. The aim of this thesis was to investigate alternative approaches and methods for the direct labelling of cells using zirconium-89. This work also describes the first use of zirconium-89 in Cambridge and the set-up of the infrastructure and methods. First, the sensitivity of detecting 89Zr-labelled cells on clinical PET systems was investigated that can inform on the minimal cellular radioactivity needed for detection in prospective clinical studies. Secondly, a peptide-based approach was developed whereby cell penetrating peptides were tested for 89Zr-labelling, purification, quality control and their in vitro properties. 89Zr-labelled peptides were subsequently employed for direct cell labelling in comparison to [89Zr]Zr-Oxine in preparation for preclinical studies.","abstract_has_math":false,"creators":["Lechermann, Laura"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gallagher, Ferdia"],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-06-26","date_published":"2021-06-26","updated_at":"2026-07-22T22:24:32Z","subjects":["Zirconium-89","Cell Tracking","Positron Emission Tomography","Direct Cell Labelling"],"languages":["eng"],"rights":[],"rights_urls":["https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000227426269","0000000347845230"],"render_values":[{"text":"0000-0002-2742-6269","href":"https://orcid.org/0000-0002-2742-6269","code":true},{"text":"0000-0003-4784-5230","href":"https://orcid.org/0000-0003-4784-5230","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.81125","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gallagher, Ferdia"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["GlaxoSmithKline PhD Studentship Cancer Research UK Scholarship"]},{"key":"dc:creator","label":"Author","values":["Lechermann, Laura"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000227426269","0000000347845230"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2021-06-26"]},{"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/1810/333705"]},{"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":["Zirconium-89","Cell Tracking","Positron Emission Tomography","Direct Cell Labelling"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.81125"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c4b65949-8194-46e8-8896-5f93e6cff782/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The use of cell-based therapies as a living drug have gained considerable attention for the treatment of a range of conditions such as genetic diseases, autoimmune disorders and cancer. The emergence of genetically engineered T cells expressing chimeric antigen receptors (CAR T-cells), together with modulations of immune checkpoints have brought the rapidly advancing field of immunotherapy into a new, revolutionary spotlight with a renewed interest in cell-based therapies. In vivo imaging and tracking of cells can be used to non-invasively improve the accuracy, efficacy and safety of novel immune-modulatory treatments and cell therapies. Positron Emission Tomography (PET) is a powerful non-invasive imaging technique that can be utilised for spatial and longitudinal tracking of different cell types. The long half-life PET isotope zirconium-89 (t1/2 = 78.4 h) has become increasingly available and [89Zr]Zr-Oxine has recently emerged as a promising candidate for direct cell labelling and longitudinal cell tracking. However, the water insolubility and synthesis method of [89Zr]Zr-Oxine may limit its implementation as a routine clinical imaging tool and little work has been performed looking at alternatives to this compound. The aim of this thesis was to investigate alternative approaches and methods for the direct labelling of cells using zirconium-89. This work also describes the first use of zirconium-89 in Cambridge and the set-up of the infrastructure and methods. First, the sensitivity of detecting 89Zr-labelled cells on clinical PET systems was investigated that can inform on the minimal cellular radioactivity needed for detection in prospective clinical studies. Secondly, a peptide-based approach was developed whereby cell penetrating peptides were tested for 89Zr-labelling, purification, quality control and their in vitro properties. 89Zr-labelled peptides were subsequently employed for direct cell labelling in comparison to [89Zr]Zr-Oxine in preparation for preclinical studies."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["ec1e9482951fd9bbe4ba0c86978762b3"]},{"key":"dc:title","label":"Title","values":["Development of 89Zirconium-PET Tracers for Immune Cell Imaging"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gallagher, Ferdia"],"dc:contributor.sponsor":["GlaxoSmithKline PhD Studentship Cancer Research UK Scholarship"],"dc:creator":["Lechermann, Laura"],"dc:creator.authoridentifier":["0000000227426269","0000000347845230"],"dc:date.issued":["2021-06-26"],"dc:description.abstract":["The use of cell-based therapies as a living drug have gained considerable attention for the treatment of a range of conditions such as genetic diseases, autoimmune disorders and cancer. The emergence of genetically engineered T cells expressing chimeric antigen receptors (CAR T-cells), together with modulations of immune checkpoints have brought the rapidly advancing field of immunotherapy into a new, revolutionary spotlight with a renewed interest in cell-based therapies. In vivo imaging and tracking of cells can be used to non-invasively improve the accuracy, efficacy and safety of novel immune-modulatory treatments and cell therapies. Positron Emission Tomography (PET) is a powerful non-invasive imaging technique that can be utilised for spatial and longitudinal tracking of different cell types. The long half-life PET isotope zirconium-89 (t1/2 = 78.4 h) has become increasingly available and [89Zr]Zr-Oxine has recently emerged as a promising candidate for direct cell labelling and longitudinal cell tracking. However, the water insolubility and synthesis method of [89Zr]Zr-Oxine may limit its implementation as a routine clinical imaging tool and little work has been performed looking at alternatives to this compound. The aim of this thesis was to investigate alternative approaches and methods for the direct labelling of cells using zirconium-89. This work also describes the first use of zirconium-89 in Cambridge and the set-up of the infrastructure and methods. First, the sensitivity of detecting 89Zr-labelled cells on clinical PET systems was investigated that can inform on the minimal cellular radioactivity needed for detection in prospective clinical studies. Secondly, a peptide-based approach was developed whereby cell penetrating peptides were tested for 89Zr-labelling, purification, quality control and their in vitro properties. 89Zr-labelled peptides were subsequently employed for direct cell labelling in comparison to [89Zr]Zr-Oxine in preparation for preclinical studies."],"dc:format.checksum.md5":["ec1e9482951fd9bbe4ba0c86978762b3"],"dc:identifier.doi":["10.17863/CAM.81125"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/c4b65949-8194-46e8-8896-5f93e6cff782/download"],"dc:language":["eng"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/333705"],"dc:rights":["https://www.rioxx.net/licenses/all-rights-reserved/"],"dc:subject":["Zirconium-89","Cell Tracking","Positron Emission Tomography","Direct Cell Labelling"],"dc:title":["Development of 89Zirconium-PET Tracers for Immune Cell Imaging"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:32Z"}