Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797242
Title: Molecular probes for understanding disease using PET and fluorescence imaging
Author: Morgan, Timaeus Edmund Francis
ISNI:       0000 0004 8503 1390
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2019
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Abstract:
During the course of this PhD, several libraries of potential PET imaging agents were synthesised for testing their affinity and selectivity for sphingosine-1-phosphate 5 receptors (S1P5). These receptors are located within oligodendrocytes and are proposed to have a major role in the re-myelination of neurons. Imaging of these receptors could lead to new treatments and diagnostic tools for the management of demyelinating disorders, such as multiple sclerosis (MS). The libraries of compounds were subject to biological evaluation and two lead compounds, fluorobenzamides 89 and 94, were identified as being the most potent and selective for S1P5 receptors. The synthesis of a further compound that was described in the literature as having high affinity for S1P5 was adapted to allow for the preparation of precursor 124 for 11C-labelling. The radiosynthesis of compound [11C]33 was then optimised. An improved synthesis of AB5186, an imaging agent for the translocator protein (TSPO),was developed. TSPO has been shown to be involved in inflammatory processes and is a biomarker for many inflammatory diseases. Evaluation of AB5186 led to the synthesis of a higher affinity compound LW223 (155), which was not sensitive to the single nucleotide polymorphism present in TSPO. A synthesis of LW223 (155) was developed that allowed for the production of two potential precursors for radiofluorination. Investigation of the radiochemistry showed a chloro-precursor was the most efficient for 18F-labelling. Finally, an investigation into a polymer-supported nitrite reagent approach for the synthesis of benzotriazole derived α-amino acids allowed the preparation of a variety of functionalised compounds in relatively few steps. Further derivatisation of these compounds led to the discovery of a benzotriazole derived α-amino acid 212 with strong fluorescence in the visible region.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.797242  DOI:
Keywords: QD Chemistry
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