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

Katie M Parkins,Ashley V Makela,John A Ronald,Paula J Foster,Yuanxin Chen,Amanda M Hamilton

doi:10.1038/srep35889

Katie M Parkins, Ashley V Makela + Show 4 more

Open Access

https://doi.org/10.1038/srep35889

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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.

Highlights

Human epicardium-derived cells (EPDCs) into the infarcted heart of immune compromised mice[10]
firefly luciferase (FLuc) bioluminescence imaging (BLI) requires adenosine triphosphate (ATP) as a cofactor and so the BLI signal is directly proportional to the number of viable cells at a particular location[11]
Given its high sensitivity and ability to provide measures of cellular viability, in this study we evaluated whether BLI can be used in conjunction with cellular MRI to follow cancer cell fate from their initial arrest in the brain to the formation of overt tumors in a well-established mouse model of breast cancer metastasis

Summary

Introduction

Human epicardium-derived cells (EPDCs) into the infarcted heart of immune compromised mice[10]. FLuc BLI requires adenosine triphosphate (ATP) as a cofactor and so the BLI signal is directly proportional to the number of viable cells at a particular location[11] This has been shown to provide corresponding information to tumour volume measurements with more structure-based imaging such as CT or MRI. We demonstrate that BLI complements well with our sensitive cellular MRI technologies, allowing us for the first time to get direct longitudinal measures of whole-brain single cell arrest, tumour volumes, and cancer cell viability, providing a more holistic view of transplanted cancer cell fate in living subjects Combining of these imaging technologies should be broadly applicable to numerous preclinical models of experimental metastasis

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