| Summary: | <p><b>Chapter One</b> introduces molecular imaging and the modalities available for oncological imaging.
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 radiolabelling of biomolecules. Finally, the chemistry and radioisotopes of copper are
described, and copper bis(thiosemicarbazonato) complexes introduced in the context of PET
imaging.</p>
<p><b>Chapter Two</b> describes the synthesis and characterisation of novel carboxylate- and maleimidefunctionalised 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.</p>
<p><b>Chapter Three</b> introduces molecular imaging 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 tumourline dependency.</p>
<p><b>Chapter Four</b> presents the synthesis of copper bis(thiosemicarbazonates), radiolabelled either at
the metal (<sup>64</sup>Cu) or at the ligand (<sup>18</sup>F or <sup>123</sup>I) for mechanistic studies. The physicochemical
characteristics of the copper complexes were measured and the complexes evaluated for their in
vitro hypoxia selectivity.</p>
<p><b>Chapter Five</b> describes in vitro and in vivo studies of the orthogonally radiolabelled complexes,
inclusive of control experiments with [<sup>64</sup>Cu]CuATSM, 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.</p>
<p><b>Chapter Six</b> contains full experimental details for the work described in this thesis.</p>
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