Doctor of Philosophy
Foster, Paula J
Introduction: The environment in which a tumour exists and functions is called the tumour microenvironment (TME). In breast cancer, the presence of tumour associated macrophages (TAMs) in the TME is associated with tumour aggressiveness and poor outcomes. Despite evidence for a link between TAM content and outcome, there are few strategies to measure TAMs and no in vivo approach. Iron or fluorine-19 (19F)-based MRI can be used to detect macrophages post intravenous injection of either an iron or perfluorocarbon (PFC) agent. Iron-based MRI is sensitive but difficult to quantify. 19F MRI is specific and signal is proportional to the number of 19F spins. 19F MRI is much less sensitive and consequently, most 19F studies have been performed at high magnetic field strengths and with long scan times. Methods: First, iron- and 19F-MRI were compared for quantification of TAMs in a murine model of breast cancer. Imaging was performed on a clinical 3T (for iron) and a preclinical 9.4T system (for PFC). Next, 19F MRI at 9.4T was employed to compare TAMs in three breast cancer models of varying aggressiveness. Finally, 19F MRI was implemented on a clinical 3T MRI. The detection limits and accuracy of 19F quantification were determined using cell samples. In vivo mouse 19F images of TAMs in mammary fat pad tumours were acquired with varying number of signal averages and a novel 19F analysis method was evaluated. Results: Iron- and 19F-based imaging revealed the same spatial distribution of TAMs in tumours, which was supported by microscopy. However, the quantification of TAMs based on signal loss due to iron, or 19F signal, produced different results. This study revealed that 19F MRI better represents TAM content. We measured significantly more 19F spins/mm3 in the most aggressive 4T1 tumours, consistent with other findings of high numbers of TAMs being associated with tumour progression and metastasis. 19F MRI at 3T could detect and quantify 19F-labeled cells in a murine tumour model. Conclusion: 19F MRI is a useful tool for imaging TAMs in vivo. This could represent an imaging biomarker for the non-invasive detection of TAMs.
Makela, Ashley V., "In Vivo Tracking of Tumour Associated Macrophages in Breast Cancer with Magnetic Resonance Imaging" (2018). Electronic Thesis and Dissertation Repository. 5959.