Theranostics 2014; 4(8):845-857. doi:10.7150/thno.8343 This issue Cite
Research Paper
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
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
*These authors contributed equally to this work.
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.
Keywords: Breast tumor initiating cells, Extra domain-B of fibronectin, Aptides, Superparamagnetic iron oxide nanoparticles, Magnetic resonance imaging.