UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Development of a neutrophil elastase specific radiotracer for imaging of inflammation

Maher, Sinéad; (2025) Development of a neutrophil elastase specific radiotracer for imaging of inflammation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of SineadMaherPhD_Thesis.pdf]
Preview
Text
SineadMaherPhD_Thesis.pdf - Accepted Version

Download (6MB) | Preview

Abstract

Inflammatory processes play a key role in protecting the body by fighting infection and injury. However, the same processes that are beneficial for the resolution of acute disease, can become detrimental when dysregulated in a wide variety of chronic diseases such as cardiovascular disease, chronic obstructive pulmonary disease, autoimmune disease, cancers and neurodegenerative disorders. In particular, neutrophils, the first cells involved in acute immune response, have been shown to play a role in pathogenesis through the formation of neutrophil extracellular traps. This process, termed NETosis, has been associated with chronic inflammation. Despite the frequent occurrence of severe inflammation in many chronic diseases, there is currently no diagnostic test available to detect associated processes, such as NETosis, in vivo in a non-invasive manner. The aim of the research presented in this thesis was to address this gap by developing a radiotracer for imaging of NETosis with positron emission tomography (PET). The enzyme neutrophil elastase, the most abundant protein in a NET, was selected as surrogate biomarker. The study was initiated with a review of current neutrophil elastase ligands to identify scaffolds with properties that are suitable for PET tracer development. Molecular docking permitted the analysis on the effect of fluorination on the binding affinity for NE. Selected fluorinated molecules were synthesised, and their affinity was assessed in vitro using a fluorometric binding assay that was set up for this purpose. The synthesis of a NE-specific PET tracer was subsequently carried out. This involved the application of sulfonium salt chemistry to the radiosynthesis of small drug-like molecules bearing peptide bonds. The synthetic strategy was tested using a known amide-containing radiotracer, [18F]FNDP, before being translated to the targeted NE ligand. The main outcome of the work is a high affinity NE-specific PET tracer candidate, which – going forward – can undergo preclinical characterisation and is expected to underpin a PET tracer discovery programme.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Development of a neutrophil elastase specific radiotracer for imaging of inflammation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
Keywords: Chemistry, PET, Neutrophil Elastase, Inflammation, Imaging agent
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10206240
Downloads since deposit
79Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item