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The use of spin traps and spin scavengers for imaging oxidative damage
[Thesis]. Manchester, UK: The University of Manchester; 2019.
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Abstract
Spin traps and scavengers have been used to detect free radicals for decades. They react with free radical molecules forming adducts that either prolong the free radical signal (spin traps) or void it (spin scavengers). This reactivity has been exploited in electron spin resonance (ESR), a technique that despite its low sensitivity it is still considered the gold standard to detect free radicals. In this thesis the aim was to test if spin traps and spin scavengers could be adapted to other analytical modalities with more sensitivity and/or quantification capabilities. The infrastructures available allowed us to consider positron emission tomography (PET) and mass spectrometry (LC-MS and imaging). Firstly the molecules were evaluated in in vitro competition experiments using LC-MS. A simple method to evaluate oxidative damage products was developed, and commercially available spin traps and scavengers were tested. The experimental results agreed with the literature pointing towards DMPO (5,5-dimethyl-1-pyrroline- N oxide) like molecules as suitable tracers. In the second results chapters three F-18 PET tracers with spin trap or scavenger reactivity were produced and tested in cell uptake experiments. The experiments were negative for uptake. The third part of the thesis was planned for investigation of the mechanism of action of the successful PET tracer but also to develop a technique that would allow the identification of radical damaged biomolecules with mass spectrometry imaging. Only a very low intensity peak could be assigned to a possible radical oxidation. The main conclusion of these experiments is that the mass spectrometry imaging (MSI) used might not have enough sensitivity and mass resolution to study these low intensity peaks. The hypothesis that spin traps and spin scavengers could be exploited with other techniques was explored in this thesis in different ways without promising results.