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Title: New copper-64 complexes for imaging hypoxia
Author: Theobald, Mark Brian Michael
ISNI:       0000 0004 2721 4439
Awarding Body: Oxford University
Current Institution: University of Oxford
Date of Award: 2010
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Chapter One gives an overview of medical imaging techniques, focusing on and comparing the nuclear imaging techniques of single photon emission computed tomography (SPECT) and positron emission tomography (PET). The applications of copper radioisotopes in nuclear medicine are presented, in particular the development of copper bis(thiosemicarbazonate) complexes for use as hypoxia imaging agents. Hypoxia and current strategies for its diagnosis are also discussed. Chapter Two describes the introduction of a new linker to bis(thiosemicarbazone) ligands along with the subsequent synthesis and characterisation of the zinc(II) and copper(II) complexes. The functionalisation with a simple amino acid as a comparison with a different linker group is discussed, along with the radiolabelling with copper-64, in vitro and in vivo uptake experiments. The synthesis and characterisation of new ligands incorporating two linker groups is described, with the in vitro hypoxia uptake investigated Chapter Three presents a series of novel asymmetric ligands replacing one thione sulphur donor in the N2S2 bis(thiosemicarbazone) donor set with alternative donors. The synthesis and properties of the zinc(II), copper(II) and nickel(II) complexes are described and compared against those of the analogous bis(thiosemicarbazonate) complexes. The radiolabelling with copper-64 of these compounds is discussed as well as in vitro and in vivo uptake experiments. Chapter Four discusses the synthesis and characterisation of new compounds with further modifications to the bis(thiosemicarbazone) core structure. New groups are introduced to one of the ligands investigated in Chapter 3 to increase its functionality and some investigations with other radiochemically relevant metals are carried out. Symmetric N4 donor ligands and their complexes are also discussed along with preliminary investigations into N-methylated thiosemicarbazone ligands. Chapter Five describes the functionalisation of bis(thiosemicarbazone) ligands with fluorophores to allow the subcellular distribution of the copper(II) complex to be explored. The use of two photon fluorescence and fluorescence lifetime imaging microscopy (FLIM) to distinguish between the bis(thiosemicarbazone) ligand and copper(II) complex in vitro is discussed. Chapter Six gives a summary of the results described in Chapters Two to Five. Chapter Seven contains full experimental details of the work presented in this thesis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available