title: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, Korea.
authors.forename: YoonSeok
authors.initials: Y
authors.lastname: Choi
authors.forename: Hoe Suk
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Cho
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Yi
authors.forename: Sung-Jong
authors.initials: SJ
authors.lastname: Eun
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jisu
authors.initials: J
authors.lastname: Woo
authors.forename: Seung Hong
authors.initials: SH
authors.lastname: Choi
authors.forename: Taeg-Keun
authors.initials: TK
authors.lastname: Whangbo
authors.forename: ChulSoo
authors.initials: C
authors.lastname: Choi
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D002462:Cell Membrane / Q000378:metabolism; D019587:Dietary Supplements; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D005293:Ferritins / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007501:Iron / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000166:cytology; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D049452:Green Fluorescent Proteins; D000077143:Docetaxel; D005293:Ferritins; D007501:Iron