Foster, Clive Edwin (1996) Tailored metal complexes for imaging applications. Doctoral thesis, Durham University.
The short-lived PET radionuclide (^134)La(t(_1/2)=6.7 minutes) is well suited to the repeated evaluation of blood perfusion, thus providing a method of following changes in tumour behaviour, in response to therapy. Ligands, both acyclic and macrocyclic, have been synthesised, and the complexes formed with (^134)La(^3+) evaluated in vitro and in vivo. Other lanthanide complexes have also been evaluated for potential use in magnetic resonance imaging and photoimmunoassay studies. A preliminary crystal structure determination of a lanthanum tetrabenzylphosphinate complex reveals the presence of one water molecule in the inner co-ordination sphere. The development of monoclonal antibodies with a specificity for the surface features of tumour cells presents a method for the localisation of a radionuclide at the tumour. Copper-64 (t(_1/2)=12.7 hours) uniquely combines the decay properties required for imaging and therapy. Ligands have been developed for derivatising antibody molecules with radioactive copper, whilst retaining specificity for the target antigen. Three modified proteins have been evaluated in vivo, and show a high tumour uptake compared with blood, but modest uptake compared with the liver, suggestive of some degree of protein denaturation during labelling. A more subtle approach has been developed, exploiting the affinity of biotin for avidin. Higher selectivity at much shorter post-administration time is potentially attainable by the use of a multi-step procedure. A copper binding ligand incorporating biotin has been synthesised. The (^64)Cu complex of the conjugate shows specificity for the protein avidin both in vitro and in vivo. The prognosis of patients with hepatoma or liver metastases is poor. A lipophilic copper complex has been synthesised and retention in the liver demonstrated in vivo. Measurements with three cell lines in vitro suggest that the complex is more readily taken up by tumour cells (and cells from metastases) compared to normal cells.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||09 Oct 2012 11:51|