Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686272
Title: Development of fluorine-18 labelled phosphonium cations for imaging apoptosis
Author: Haslop, Anna
ISNI:       0000 0004 5918 3577
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Abstract:
This thesis details the development and testing of a new library of phosphonium cation-based tracers for imaging apoptosis. The research aims to utilise the favourable conditions of the CuAAC reaction to readily radiolabel a series of phosphonium cations bearing an 18F labelled triazole moiety. The synthesis of the alkyne-phosphonium salts required for both reference compounds and the 18F labelled tracer, focusing on the carbon chain length and the functionalisation of the phenyl rings is described (Chapter 3). The reference compounds for seven newly proposed tracers were also successfully synthesised and discussed in Chapter 3. A fully automated set-up was designed and implemented to synthesise the library of novel 18F labelled phosphonium cations and is discussed in Chapter 4. The Advion NanoTekĀ® LF micro-fluidic system was implemented to successfully synthesise the well-known 18F precursor, [18F]fluoroethylazide. Following this, the CuAAC reaction and purification via semi-prep HPLC afforded all seven tracers in high radiochemical purity. The range of lipophilicities was also determined by measuring the log D of each tracer. The synthesis of producing two or more tracers in one reaction vial is then described. The final two results chapters detail the in vitro and in vivo analysis that was carried out. Cellular assays were used to determine the uptake of the tracer which was found to be in relation with the tracer's lipophilicity. Treatment with Cisplatin and the protonophore, CCCP was investigated and the results seen lead to the in vivo assessment of two of the tracers. Chapter 6 discusses the results obtain from the metabolic stability, biodistribution and PET/CT scanning studies for both tracers and compares the findings.
Supervisor: Long, Nicholas ; Plisson, Christophe ; Gee, Antony Sponsor: Biotechnology and Biological Sciences Research Council ; GlaxoSmithKline ; Imanova
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.686272  DOI: Not available
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