The investigation of alanine/EPR dosimetry, dose enhancement caused by AuNPs and the novel synthesis of bimetallic-nanoparticles via neutron capture

This thesis investigated five key areas, which are each presented as a chapter, with the major aims and findings summarized below: 1.The dose enhancement (DE) levels caused by secondary electron emissions from gold nanoparticles (AuNPs) were investigated by impregnating spherical AuNPs of varying sizes (1.9, 5 & 15 nm) and concentrations (3, 2 and 1 %) within the dosimeter alanine. The AuNP/alanine composites were irradiated alongside control pellets (alanine) with different quality beams (kV and MV X-rays, electrons and protons) and the yield of alanine radicals quantified by Electron Paramagnetic Resonance (EPR) spectroscopy. For X-rays (kV and MV) increasing AuNP concentration yielded increased DE, and was greatest for kV X-rays overall (55 % DE for 3 %, 5nm AuNP /alanine composites, which decreased to 15 % DE for the 1 %-composites). Similarly, the effects of AuNP size on DE levels was clearer for kV X-ray irradiations with a preference for the smaller 1.9 nm sized AuNPs. Whilst MV X-ray irradiations did show the same AuNP size preference, the effects of concentration were more noticeable on DE, which was consistent with the literature. Irradiations with charged particles; electrons (6 MeV) and protons (150 MeV) showed no such dependence on either AuNP concentration or size and consistently yielded DE levels of ≤ 9 % (electrons) and ≤ 5 % (protons). These results agree well with recent Monte Carlo simulations, (which report little to no secondary electron production) and support cell and animal studies for AuNPs irradiated with protons that suggest the higher DE seen (ca.15 to 20 %) is due to other processes, such as; the production of reactive oxygen species (ROS) generated from the aqueous media in cells. 2.The suitability of IRGANOX®1076 as a near-tissue equivalent radiation dosimeter was investigated for various radiotherapy beam types; kV and MV X-rays, electrons and protons over clinically-relevant doses. Pellets consisting of solid solutions of IRGANOX®1076 in wax (IWSS) were manufactured, which yielded a single EPR peak after exposure to ionising radiations, and was attributed to the phenoxyl radical obtained by net loss of H•. Whilst, irradiation of solid IRGANOX®1076 produced a doublet signal, consistent with the formation of the phenol cation radical, obtained by electron loss. The IWSS pellets gave reliable dose measurements for exposures as low as 2 Gy, and a linear dose response for all types of radiations examined. Post- measurements for proton irradiations (up to 77 days) indicate good signal stability with minimal signal fading (between 1.6 to 3.8 %), and no significant change with the orientation of the sample. Overall, IWSS pellets are ideal for applications in radiotherapy dosimetry, and can easily be prepared in wax and moulded to different shapes. 3.Alanine is well known to have an EPR angular dependant response which alters its peak amplitudes. It is understood that water bound within alanine affects the EPR cavities resonance and promotes radical transformations causing signal variation. Means to overcome this include; averaging several measurements at different angles within the cavity, and using an internal EPR standard. This work examined an alternative method using alanine pellets manufactured with the binder (paraffin wax) as the bulk material (approximately 90 %) with alanine dispersed within (approximately 10 %). The sensitivity of the amplitude EPR signal when rotated within the cylindrical axis of the EPR cavity was investigated, with alanine-wax pellets showing a deviation range of; 1.14 to 2.06 % (3 days post-irradiation), which was comparable to commercial alanine pellets; 0.95 to 1.91 %. After approximately 30 days post-irradiation, the wax-alanine pellets remained stable, without being stored in a controlled environment; 1.56 to 1.93 %, whilst the commercial pellets deviation range had increased; 2.04 to 3.18 % despite being kept in a controlled environment. This simple method offers an alternative means to overcome EPR signal variation, without having to store the wax-samples in a highly controlled environment. 4.Currently alanine dosimeters are limited in their potential use in radiotherapy, mainly by poor sensitivity at low radiation doses (< 5 Gy), which was addressed in this work by implementation of a new protocol called ‘spiking’. A set of alanine dosimeters were ‘spiked’ with a large dose of radiation, (approximately 30 Gy of 6 MV X-rays) then subjected to additional doses ranging between 0.5 and 10 Gy. The radical yield obtained following exposure to ionising radiation was measured by EPR spectroscopy and quantified using the central peak of the alanine radical species. After subtraction of the contribution from the 'spike' dose, a linear correlation between both the dose and the area of the central EPR signal was obtained for doses of 0.5 Gy (regression value of 0.9890), and for the central peak’s amplitude (regression value of 0.9895). Overall, this method allowed quantification of doses as low as 0.5 Gy, and offers many advantages as a technique; it is easy to perform, requires no complex EPR signal analysis, and (by the addition of a large spike dose) is not susceptible to baseline distortions at low doses (<10 Gy), and may extend the current usage of alanine dosimeters in radiotherapy. 5.Finally, the novel formation of the bimetallic nanoparticle (BiMetNP); AuHgNP by neutron capture was investigated. Neutron bombardment of AuNPs was completed at ANSTO, with gamma spectrum analysis confirming the formation of the unstable 198Au isotope. After a sufficient decay time, inductively coupled plasma mass spectroscopy (ICP-MS) positively identified the stable 198Hg isotope, thus confirming the formation of the BiMetNP product. Analysis of the γ-decay of the unstable 198Au isotope was perfumed and quantified over time (1 to 10 hours) using thermo luminescent dosimeters (TLD100s), OSL (optically stimulated luminescence) nanoDots® and Gafchromic films (EBT3 and RTQA2-1010), with good agreement between all techniques. These confirm that neutron bombardment of a mono-metallic-nanoparticle offers an alternative means to synthesize alloy-type BiMetNP products, which are not readily formed using current wet-chemistry methods (which favour a core and layer BiMetNP product). Furthermore, the γ- decay of the 198Au isotope has potential as a theranostics agent, capable of emitting a localised radiation dose at a tumour site, whilst simultaneously allowing real time imaging.