Comparing the Fate of Brain Metastatic Breast Cancer Cells in Different Immune Compromised Mice with Cellular Magnetic Resonance Imaging

Abstract

25Metastasis is the leading cause of mortality in breast cancer patients, with brain metastases becoming increasingly 26 prevalent. Studying this disease is challenging due to the limited experimental models and methods available. Here, 27 we used iron-based cellular MRI to track the fate of a mammary carcinoma cell line (MDA-MB-231-BR) in vivo to 28 characterize the growth of brain metastases in the nude and severely immune-compromised NOD/SCID/ILIIrg-/-29 (NSG) mouse. 30Nude and NSG mice received injections of iron-labeled MDA-MB-231-BR cells. Images were acquired with a 3T 31MR system and assessed for signal voids and metastases. The percentage of signal voids and the number and volume 32 of metastases were quantified. Ex vivo imaging of the liver, histology, and immunofluorescence labeling was 33 performed. 34On day 0, iron-labeled cells were visualized as signal voids throughout the brain. The percentage of voids decreased 35 significantly between day 0 and endpoint. At endpoint, there was no difference in the number of brain metastases or 36 tumour burden in NSG mice compared to nudes. Tumour volumes in nude mice were significantly larger than in 37 NSG mice. Body images indicated that the NSG mice had metastases in the liver, lungs, and lymph nodes. 38Characterization of the NSG and nude mouse is necessary to study breast cancer brain metastasis in vivo. Here, we 39 show that the 231BR cell line grew differently in NSG mice compared to nude mice. This work demonstrates the 40 role that imaging can play toward credentialing these models that cannot be done with other in vitro or 41 histopathologic methods alone. 42 43

A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation

“…The addition of the magnetic plate for labeling was likely ineffective due to the fact that the majority of these cells are in suspension during labeling, which differs from most studies which have labeled adherent cells. Previous work by our group has shown that this concentration of MPIO effectively labels immortalized cancer cells for the purposes of cell tracking (38), however, the methods of labeling described in this work varies from the traditional labeling protocol of adherent cells due to the differences in homogeneity and complex cell culture required to grow PDX cells. Future work will investigate labeling trials with different iron particles and whether this changes the visualization of these cells in vivo with MPI or MRI.…”

A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation

“…The addition of the magnetic plate for labeling was likely ineffective due to the fact that the majority of these cells are in suspension during labeling, which differs from most studies which have labeled adherent cells. Previous work by our group has shown that this concentration of MPIO effectively labels immortalized cancer cells for the purposes of cell tracking [ 30 ]. However, the methods of labeling described in this work varies from the traditional labeling protocol of adherent cells due to the differences in homogeneity and complex cell culture required to grow PDX cells.…”