title: MRI of breast tumor initiating cells using the extra domain-B of fibronectin targeting nanoparticles.
abstract: The identification of breast tumor initiating cells (BTICs) is important for the diagnosis and therapy of breast cancers. This study was undertaken to evaluate whether the extra domain-B of fibronectin (EDB-FN) could be used as a new biomarker for BTICs and whether EDB-FN targeting superparamagnetic iron oxide nanoparticles (SPIONs) could be used as a magnetic resonance imaging (MRI) contrast agent for BTIC imaging in vitro and in vivo. BTICs (NDY-1) exhibited high EDB-FN expression, whereas non-BTICs (MCF-7, BT-474, SUM-225, MDA-MB-231) did not exhibit EDB-FN expression. Furthermore, Cy3.3-labeled EDB-FN specific peptides (APTEDB) showed preferential binding to the targeted NDY-1 cells. To construct an EDB-FN targeted imaging probe, APTEDB was covalently attached to a thermally cross-linked SPION (TCL-SPION) to yield APTEDB-TCL-SPION. In the in vitro MRI of cell phantoms, selective binding of APTEDB-TCL-SPION to NDY-1 cells was evident, but little binding was observed in MCF-7 cells. After the intravenous injection of APTEDB-TCL-SPION into the NDY-1 mouse tumor xenograft model, a significant decrease in the signal within the tumor was observed in the T2*-weighted images; however, there was only a marginal change in the signal of non-targeting SPIONs such as APTscramble-TCL-SPION or TCL-SPION. Taken together, we report for the first time that EDB-FN was abundantly expressed in BTICs and may therefore be useful as a new biomarker for identifying BTICs. Our study also suggests that APTEDB-TCL-SPION could be used as an MRI contrast agent for BTIC imaging.
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea ; 2. Department of Radiology, Yanbian University Hospital, 1327 JuZi Street, Yanji City, JiLin Province 133000, China.
authors: Yujin
authors: Y
authors: Sun
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Hoe Suk
authors: HS
authors: Kim
authors: 3. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors: Jinho
authors: J
authors: Park
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Mulan
authors: M
authors: Li
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Lianji
authors: L
authors: Tian
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: YoonSeok
authors: Y
authors: Choi
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Byung Ihn
authors: BI
authors: Choi
authors: 3. KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors: Sangyong
authors: S
authors: Jon
authors: 1. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea.
authors: Woo Kyung
authors: WK
authors: Moon
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003911:Dextrans; D005260:Female; D005353:Fibronectins / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057446:Hydrodynamics; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010316:Particle Size; D017434:Protein Structure, Tertiary
chemical_list: D003911:Dextrans; D005353:Fibronectins; D058185:Magnetite Nanoparticles; C065507:ferumoxides
keywords: Aptides; Breast tumor initiating cells; Extra domain-B of fibronectin; Magnetic resonance imaging.; Superparamagnetic iron oxide nanoparticles