Investigating Cellular Imaging Techniques for Cancer Cell Tracking
Abstract
Introduction: Breast cancer remains a leading cause of mortality among women due to the propensity of breast tumours to spread and metastasize to distant sites, including the brain. Early detection of metastatic disease has been challenging, and typical methods of treatment often fail. A significant roadblock in advancing the detection and treatment of breast cancer brain metastases is the lack of representative experimental preclinical models and methods of studying its progression in vivo. Methods: First, we use iron-based cellular MRI to noninvasively track the progression of a brain metastatic breast cancer cell line in murine models with varying immune competencies. We then employ longitudinal BLI and MPI to visualize the tumour progression of a patient-derived xenograft (PDX) model of breast cancer brain metastasis. Finally, we used MPI to evaluate the magnetic performance of iron oxide particles following cell labeling with a brain metastatic breast cancer cell line to optimize cellular detection and cell tracking techniques. Results: Cellular MRI revealed significant differences in tumour progression throughout the brain and body between murine models. We then developed a novel method for labeling PDX cells with iron oxide particles and use MPI and BLI to provide measures of iron content and cellular viability. Finally, we demonstrate that cell labeling can change the magnetic performance of iron agents used for cell tracking with MPI. Conclusion: Comprehensive analysis of cancer cell arrest, clearance, and tumour progression with cellular imaging is important for understanding the metastatic cascade of a model of breast cancer brain metastasis in both cell lines and PDX models. Furthermore, we provide evidence that iron oxide particles are valuable tracers for MPI cell tracking, but their MPI performance may be altered following cell labeling.