Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Collaborative Specialization

Molecular Imaging

Supervisor

Ronald, John A

2nd Supervisor

Foster, Paula J

Co-Supervisor

Co-Supervisor

Abstract

Magnetic Particle Imaging (MPI), a novel imaging technology, offers hotspot visualization and quantification of superparamagnetic iron oxide (SPIO) labelled cells in vivo. Bioluminescence imaging (BLI), with the sensitive reporter Akaluc, can provide complementary information on cell viability and proliferation. Here, we combined MPI, and Akaluc BLI for a more holistic picture of cancer cell fate in mice. Breast cancer cells labelled with Akaluc and the SPIO Synomag-D, were injected into the mammary fat pad (MFP) of mice and imaged on BLI and MPI for 2-weeks. Over this period, BLI signal increased due to tumour progression, while MPI signal decreased due to probe dilution in proliferating cells. Both modalities detected metastases, however, they were visualized in different locations. Overall, Akaluc BLI complemented MPI, providing sensitive detection of distant metastases, and longitudinal measures of cell viability. This multimodal approach should improve our understanding of metastasis, and aid development of novel therapeutics.

Summary for Lay Audience

The purpose of this thesis is to combine two imaging tools to help visualize cancer cells injected into mice. Magnetic particle imaging or MPI, is a new imaging system which can directly detect and quantify iron particles. Cells can be labelled with these iron particles and tracked throughout the body. However, when cells divide, the amount of iron within each cell gets diluted, and may get dispersed throughout the body. Additionally, dead cells will continue to produce a signal. For these reasons MPI cannot be used to study cell proliferation or viability. We believe that bioluminescence imaging or BLI would nicely complement MPI as it can be used to measure both proliferation and viability over long durations. One major limitation of BLI however, is that the light used in BLI gets absorbed by various tissues, reducing the signal which can be detected. This makes it very difficult to see areas deep inside the body. A solution to this is to use a reporter which produces near infrared light (NIR), as it is absorbed in lower amounts than visible light. Recently the BLI reporter Akalumine was developed, which when in contact with the enzyme Akaluc, produces NIR light. This project combines MPI with Akaluc BLI to track cancer cells injected into mice. Described in chapter 2, breast cancer cells were labelled with both iron particles and Akaluc, and then injected into mice. Following this, MPI and BLI scans were taken for 2-weeks. MPI and BLI signals were compared to determine the strengths and limitations of each, as well as to determine how they complemented each other. Chapter 3 highlights the limitations of this work, and the future directions of this project.

Available for download on Wednesday, June 01, 2022

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