Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Paula Foster

Abstract

Most breast cancer related deaths are caused by the spread or metastasis of the primary tumor to distant sites in the body. The lymph nodes are one of the first places where metastases can be detected and are frequently examined for macroscopic metastases to help determine course of treatment for patients. However, little is known about the significance of microscopic metastases and disseminated individual cancer cells within the nodes. The goal of this work was to use MRI to monitor the development of primary tumors and lymphatic metastases in models of breast cancer.

In this thesis, we examined the MRI appearance of lymph nodes in several different strains of immune compromised mice (nude, CB -17 SCID, NOD/SCID IL2Rnull) and compared the appearance to immune competent C57/Bl6 strain. We found that immune deficiencies influenced the MRI appearance of nodes and that the nude strain had highly variable lymph node appearance and volume. We also compared orthotopic transplantation models of breast cancer that used both the nude and CB-17 SCID strains using MRI. We found that MRI was most reliable for detecting metastases in the lymph nodes of SCID mice and that the variability of the appearance of nodes in nude mice can lead to their misclassification. We then used the SCID orthotopic breast cancer model to monitor the appearance and retention of iron oxide nanoparticle labeled cancer cells in both the primary tumor and lymph nodes. We found that iron-labeled cells are still detected within the primary tumor after 28 days post-implantation and that these labeled cells almost exclusively migrated to the lymph nodes.

The development of improved methods for monitoring the development of the primary tumor and metastases and the roles that different cells populations have in these processes will allow for more accurate knowledge of how cancer cell heterogeneity impacts disease progression. These tools will allow for more effective monitoring of the treatment effect of new drugs on primary tumors and metastatic dissemination.


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