Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656366
Title: Synthesising nucleoside analogues for imaging proliferation in cancer and other biomedical applications
Author: Doepner, Andreas
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Abstract:
Rapidly proliferating cells, such as cancerous cells, show increased reliance on deoxyribonucleic acid (DNA) salvage pathways for producing nucleotides required for DNA synthesis. As such targeting these salvage pathways using radiolabelled nucleosides can provide a means of imaging the extent of proliferation within a tissue using positron emission tomography (PET). This permits the detection of malignant growths. Thiothymidine and 2'-deoxy-2',2'-difluoro nucleoside analogues are currently being evaluated for theoretically superior properties in comparison to 3'-deoxy-3'-[18F]-fluorothymidine (FLT), the current standard PET proliferation marker. Investigations towards the design and synthesis of radiolabelled analogues of these nucleosides for evaluation as PET tracers were carried out. Synthesis and radiosynthesis of the 2',2'-difluoro nucleoside analogue i was completed using a Stille coupling to introduce the carbon-11 radiolabel. The synthesis of ii, a precursor to a carbon-11 methylated gemcitabine analogue and iii, an intermediate in the synthesis of thiothymidine nucleosides are also reported. [Molecular diagram appears here. To view, please open pdf attachment] Based on the synthetic route developed for accessing iv an analogue of ii suitable for radiolabelling with fluorine-18, a series of difluoro nucleoside analogues with potential uses in PET, HIV therapy and fluorescent imaging were also synthesised v-viii. [Molecular diagram appears here. To view, please open pdf attachment].
Supervisor: Barrett, Anthony; Abaogye, Eric Sponsor: Engineering and Physical Sciences Research Council ; Department of Health ; Cancer Research UK ; Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.656366  DOI: Not available
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