A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

Abstract

Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade.

Multimodality cellular and molecular imaging of concomitant tumour enhancement in a syngeneic mouse model of breast cancer metastasis

“…By engineering cells to express a luciferase reporter, bioluminescence imaging (BLI) can provide a direct readout of cell viability in dividing cell populations. Overall, as recently described 18 , combining our highly sensitive cellular MRI tools and BLI yields complementary information on the fate of metastatic cancer cells in preclinical models. As others have pointed to a role of the immune system in CTR/CTE and differences in primary tumour effects have been seen across models of the same cancer type 8 , the purpose of this study was to apply our multimodality imaging tools to study whether CTR/CTE effects are present in the syngeneic 4T1 immune competent mouse model of breast cancer metastasis.…”

Characterization of an Orthotopic Rat Model of Glioblastoma Using Multiparametric Magnetic Resonance Imaging and Bioluminescence Imaging

“…In fact, many rats displayed a decrease in BLI signal while tumor volume continued to increase or remained stable. Previous studies have reported a linear relationship between tumor volume and BLI signal for glioma models, whereas other studies have shown a lack of a relationship ( 35 – 39 ). In particular, Jost et al reported a small subset of animals ( n = 2) showing decreased BLI signal despite increasing tumor volume and contributed it to hemorrhage and necrosis ( 39 ).…”

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

“…While we acknowledge that there is potential for immune cell uptake of the iron oxide nanoparticles that may be released by dead cancer cells, we believe that the majority of the signal voids that remain present are live cancer cells retaining iron. For example, in Parkins et al [39] we investigated this mouse model using luciferase-positive 231BR cells and measured a strong correlation on day 0 between the number of signal voids detected in day 0 brain MR images and the brain signal measured in bioluminescence images, which is only detected from viable cells, providing evidence that signal voids represent live iron-labeled cells. In Hamilton et al [41] we used fluorescence activated cell sorting ( FACS) to successfully isolate live 231BR cells that were GFP-positive and labeled with red fluorescent (Flash Red) MPIO from the brains of mice.…”