Noninvasive Identification of Viable Cell Populations in Docetaxel-Treated Breast Tumors Using Ferritin-Based Magnetic Resonance Imaging

Abstract

Background: Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics. Methodology/Principal Findings: In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking of BCSC-derived populations. No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R-2* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R-2* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R-2* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24- cells. Conclusions/Significance: These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.