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Superparamagnetic Iron Oxide Nanoparticles: foundations for novel bioconjugate species and multimodal contrast agents

Roberts, Geraint Rhys Dafydd 2018. Superparamagnetic Iron Oxide Nanoparticles: foundations for novel bioconjugate species and multimodal contrast agents. PhD Thesis, Cardiff University.
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Abstract

The properties of superparamagnetic iron oxide nanoparticles (SPION) have led to them being a major area of research within the ‘nano-revolution’. A number of SPION species have been used in disease imaging, including multimodal contrast agents active in positron emission tomography (PET) and magnetic resonance imaging (MRI), as well as bioconjugate species where biomolecules have been immobilised on the nanoparticle’s surface. The western world faces an epidemic of conditions for which monoclonal antibodies (mAbs)have become seen as a ‘magic bullet’. However, the expense of mAb therapy, possible side effects and the desire to maximise treatment success require improvements in patient stratification and selection. Chapter 1 introduces the field of biomedical imaging and immunotherapy and describes how research into immunoPET and PET/MRI imaging overlap in the following chapters. Chapter 2 describes the development of reliable, reproducible methods of synthesising SPION and introducing a number of biocompatible coatings with useful functionalities. These techniques underlie the chemistry to be discussed in Chapter 3- the immobilisation of biomolecules on the surface of SPION. Typical linker chemistry is discussed, with the relative merits of different approaches expanded upon. The effect of initial reaction stoichiometry on enzymatic activity is explored as a model for later experiment design. Chapter 4 incorporates several of the aspects examined in earlier chapters to describe the synthesis of radiolabelled SPION bioconjugated to the clinically approved antibody trastuzumab to give a novel immunoPET contrast agent. Fluorescence activated cell sorting (FACS) analysis and fluorescence microscopy confirm the in vitro validation of these agents. In vivo experiments show how these agents require further development before reaching a human clinical context. Chapter 5 relates the effort to synthesise novel coordination systems based on the hypoxiaselective imaging agent 64Cu-ATSM. The co-ordination chemistry of these systems with several metals is described.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Funders: Ser Cymru
Date of First Compliant Deposit: 19 April 2018
Last Modified: 02 May 2019 02:31
URI: http://orca-mwe.cf.ac.uk/id/eprint/110803

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