Abstract
The aim of the research documented in this thesis was to investigate molecular imaging using a MARS spectral scanner. This scanner is a photon-counting computed tomography (CT) system that simultaneously measures 5-8 energies. It operates in the clinical diagnostic energy range (30-120 keV) and at high spatial resolution (50-200 µm). The technique enables differentiation of multiple high atomic number (high-Z) materials and human tissues (calcium and water) from data obtained in a single exposure.
Four potential clinical applications were investigated. In each application, a high-Z pharmaceutical was used to identify and quantify disease-related tissue. They were: (1) iodine, a clinically available contrast, was used to segment healthy and disease-related tissue in an ex-vivo lung mouse model of chronic tuberculosis. Lung segmentation was validated using micro-CT. (2) Gold nanoparticles functionalised with monoclonal antibodies were used to target two different cancer cell types (breast and lymphoma) in a cross-over study. Compared to the control nanoparticles, uptake of gold nanoparticles targeted to specific cancer cells increased five-fold, demonstrating highly specific and quantitative molecular imaging. (3) Hafnia (hafnium oxide) nanoparticles targeted to bone microcracks were investigated in ex-vivo and murine models. An increase in accumulation of the targeted hafnia nanoparticles compared to the non-targeted nanoparticles was observed. (4) Hafnia nanoparticles packed inside probiotics were imaged within the gastrointestinal (GI) tract in-vivo. A key finding was that the bio-functionalised hafnia nanoparticles withstood the harsh environment of the GI tract, thus, have the potential to be used as a patient-friendly, orally delivered contrast. In summary, spectral photon-counting CT for quantitative molecular imaging was shown to be feasible using MARS scanners. MARS imaging was able to assess pathology at high resolution and evaluate novel nanoparticle-based contrast agents and delivery of anti-cancer drugs. Targeted nanoparticle contrast provides highly specific three-dimensional imaging of various diseases. In addition, quantifying drug delivery could provide a means to accelerate the development of new drug therapies, for example, for infectious disease and cancer. More precise diagnosis, monitoring of therapy efficacy, and the development of new and more effective drugs could also be made possible.