Ricketts, K.P.M.; (2012) Nanoparticles for tumour diagnostics. Doctoral thesis , UCL (University College London).

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Abstract

X-ray fluorescence techniques have proven beneficial for identifying and quantifying trace elements in biological tissues. A novel approach has been developed that employs x-ray fluorescence with an aim to locate the presence of nanoparticles, such as gold, which are embedded into tissues. The nanoparticles can be functionalised to act as markers for tumour characteristics to map the disease state, and then imaged to inform cancer therapy regimes. The uptake of nanoparticles by cancer cells could also enable detection of small clusters of infiltrating cancer cells which are currently missed by commonly used imaging modalities. The novel system, consisting of an energy resolving silicon drift detector with high spectral resolution, and a synchrotron source, showed potential in both quantification of and sensitivity to nanoparticle concentrations typically found in tumours. A linear relationship between fluorescence intensity and nanoparticle concentration was found down to 0.001 mgAu/ml, the detection limit of the system. A successful translation using a more clinically available bench-top x-ray tube was demonstrated, and found not to degrade the linearity or detection limit. The achieved system sensitivity suggests clinical usefulness in measuring tumour uptake in vivo. A set of bio-phantoms consisting of collagen type 1 gel, populated with colorectal cancer cells (HT29) and healthy murine fibroblast cells (3T3) that have been incubated with gold nanoparticles (GNPs), were created. The bio-samples were successfully used to (i) demonstrate GNP uptake in cells, and (ii) demonstrate the use of the novel benchtop system in measuring GNP uptake in cells. Translation to a 2D imaging technique was undertaken, using polycapillary optic technology to acquire positional information of gold XRF emissions, and energy resolving single channel and pixellated detectors. The GNP-imaging capabilities of the XRF technique were demonstrated using Perspex phantoms incorporating different GNP concentrations. Details of phantoms with concentrations as low as 0.025 mgAu/ml have been successfully imaged, with potential to image lower concentrations. It can be inferred from feasibility data collected that the x-ray fluorescence technique can be combined with x-ray diffraction methods to form a novel multi-modality system that is sensitive to GNP distribution and can discriminate biological tissue. Future work will develop this combined system to locate tumours and provide information on tumour characteristics.

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