Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558314
Title: Radiolabelled copper complexes for cancer imaging
Author: Hueting, Rebekka
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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Abstract:
Chapter One introduces molecular irnaging and the modalities available for oncological irnaging. The radioisotopes and imaging agents for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are discussed together with the bifunctional chelator approach for radio labelling of biomolecules. Finally, the chemistry and radioisotopes of copper are described, and copper bis(thiosemicarbazonato) complexes introduced in the context of PET irnaging. Chapter Two describes the synthesis and characterisation of novel carboxylate- and maleirnide- functionalised bis(thiosemicarbazonates) and their conjugation to biologically active molecules. Radiolabelling of a chelator-bombesin conjugate demonstrated site-specific labelling at room temperature and preliminary in vitro and in vivo studies confirmed its potential as an imaging agent. Bioconjugation to a model protein and subsequent radiolabelling was also investigated. Chapter Three introduces molecular irnaging of hypoxia with a focus on CuATSM. An overview of the currently accepted mechanism of hypoxia selectivity is presented. The emphasis is placed on the relationship between oxygenation status, uptake and retention which display cell- and tumour- line dependency. Chapter Four presents the synthesis of copper bis(thiosemicarbazonates), radiolabelled either at the metal (64CU) or at the ligand e8F or 123n for mechanistic studies. The physicochemical characteristics of the copper complexes were measured and the complexes evaluated for their in vitro hypoxia selectivity. Chapter Five describes in vitro and in vivo studies of the orthogonally radiolabelled complexes, inclusive of control experiments with [64Cu]CuATS~, the radiolabelled proligand and [64CU]CU2+ salts. In vitro cellular assays, as well as in vivo biodistribution studies including dynamic PET and SPECT were performed. Stability studies contrasting the in vitro and in vivo behaviour were carried out. The collective data suggest that the currently proposed redox trapping mechanism might not provide a full understanding of the factors governing biodistribution and tumour uptake. Chapter Six contains full experimental details for the work described in this thesis.
Supervisor: Gouverneur, Veronique ; Dilworth, Jonathan R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.558314  DOI: Not available
Keywords: Inorganic chemistry ; Co-ordination chemistry ; Oncology ; Organic chemistry ; bis(thiosemicarbazones) ; copper-64 ; hypoxia ; orthogonal radiolabelling
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