Abstract
The use of three gamma annihilation as a new PET molecular imaging modality which can predict tumour hypoxia was proposed by Kacperski and Spyrou in 2004. The positronium and its annihilation, could then serve as an oxygen-sensitive marker. The relative magnitude of three photon annihilation is increased in an oxygen deficient environment. The main questions addressed in this thesis are the potential use of the lanthanum bromide LaBr3:Ce (5%) scintillator detector for three-photon positron annihilation measurements. Also, the optimum source-to-detector distance that achieves good efficiency and sensitivity of the measurements. The other question is finding the best method to prepare in vitro three types of hypoxic samples (mineral water, defibrinated horse blood and serum). In addition, the suitability of the hydrophilic material is examined in terms of hydration behaviour, radiation and physical properties, for use as a phantom that represents the hypoxic tumour in the three-photon positron annihilation measurements. The main critical question is which the best method that could be used to measure the three-photon positron annihilation yields. Also, how does the 3y/2y ratio vary with different oxygen concentrations in different hydrophilic materials? Lanthanum bromide LaBr3: Ce (5%) scintillator detectors have good fast timing resolution, good stopping power and large light output. The LaBr3:Ce (5%) has very good scintillator characteristics, combining high effective Z and density, fast decay time, light emission wavelengths matching that of commonly available photon detectors and excellent energy resolution (~3% at 662 keV). However, it is highly hygroscopic in nature, making it difficult to produce, but its commercial availability has been gradually increasing in recent times. LaBr3: Ce (5%) has come to be accepted for the superior energy resolution it offers. Therefore, LaBr3: Ce (5%) detectors can be considered as the scintillators of choice for determining the yield of 2-and3-y positron annihilation. The characterisation of the detector used was carried out in terms of energy resolution and efficiency. The effect of amplifier parameters on the energy resolution was also studied. The geometrical solid angles subtended by the source-to-detector distances play an important role in the sensitivity and accuracy of the detector efficiency measurements. Therefore, the efficiency measurements were investigated at various distances to optimise the geometrical solid angle for the LaBr3: Ce (5%) detector for the three photon annihilation measurements. The experimental data were compared with the GATE simulated results obtained. The objective to study the factors that affect dissolved oxygen (DO) in three types of samples (mineral water, defibrinated horse blood and serum) was to investigate the 3y/2y ratio in hypoxic, normoxic and hyperoxic conditions of tissues for future application in oncology in the detection and quantification of tumour hypoxia. This was achieved by measuring the DO, pH and temperature before, during and after treating the samples with nitrogen, carbon dioxide and ascorbic acid (AnaeroGen). Two methods for the preparation of the in vitro hypoxic samples were investigated and evaluated. Carbon dioxide proved to be most effective for the reduction of DO in the samples. Blood tended to resist DO reduction since it decreased at a much slower rate than in water and serum. Together with the fact that the oxygen level in blood remained low after the end of exposure to the gases and ascorbic acid suggests that the solubility of oxygen in blood depends upon the concentration of haemoglobin as well as upon ligands such as CO2. CO2 combines with haemoglobin affecting oxygen binding and forms bicarbonate which further decreases the affinity of haemoglobin to oxygen Hydrophilic materials which refer to a group of cross-linked polymers originally developed in the 60s to produce soft contact lenses are characterised by equilibrium water uptake in the range 15-95 %by wet weight when hydrated in water or normal saline solution at 25°C. This ability to absorb controlled amounts of water makes them suitable human tissue substitutes. Tissue substitute phantoms of known oxygen content are therefore required in order to measure the ratio of 3-to-2 annihilation photons. The hydration behaviour in defibrinated blood and serum of two types of hydrophilic materials, as potential candidates for the construction of phantoms for radiation measurements, was also studied. The results indicate that the hydration rate is generally higher in serum. The hydration rates for blood and serum were quite similar for sample A, which had an equilibrium water content of 38%; the diffusion coefficients were found to be 0. 018 g/h in blood and 0. 019 g/h in serum. For sample B, which had an equilibrium content of 75%, the hydration rate was different for blood and serum; the diffusion coefficients were found to be 0. 055 g/h in blood and 0. 061 g/h in serum. In addition, the linear attenuation coefficient and mass attenuation coefficient were calculated in order to study the transmission and scattering behaviour of the hydrophilic material. The scatter-to-peak ratio was determined by selecting five scattering angles to study how the ratio varies with attenuating material. It may be possible that the combination of the scatter-to-peak ratio method for determining the depth of a positron-emitting radionuclide source in combination with measurement of the relative ratio of 3-to-2 photon annihilations may suggest a new technique which can locate hypoxic tumours without the necessity of further tomography just by using the information in the photon annihilation spectra recorded. Finally, the relative 3/2 photon annihilation yield was obtained for the spectrum of the point source 22Na positron emitter by using a LaBr3: Ce(5%) detector. The relative 3y/2y yields obtained for the peak-to-peak method in different hydrophilic (A, B, C, and D) materials was 0.9 ± 0.5 x 10-2 , 0.2 ± 0.3 x 10-2, 0.1± 0.9 x 10-2 and 0.7 ± 0.8 x 10-2, respectively. The highest relative yield of 3y/2y photon annihilation was obtained in hydrophilic A1 and D1 samples which have low percentage of water uptake 38% and 57% respectively. It was concluded that oxygen transmissibility, free water content and free-to-bound water ratio are increased when the water content of hydrophilic material is increased. In the other experiment, the highest relative 3y/2y yields was obtained by using 0. 5 mm aluminium (as reference material) with hydrophilic samples A and B and founded to be 0.122 ± 0.011 and 0.065 ± 0.00041, respectively.