Non-invasive Imaging of Endothelial Progenitor Cells in Tumor Neovascularization Using a Novel Dual-modality Paramagnetic/Near-Infrared Fluorescence Probe

• Type of Material: Article
• Authors: Xin-Yi Wang, Southeast University, China; Shenghong Ju, Southeast University, China; Cong Li, Fudan University; Xin-Gui Peng, Southeast University, China; Alex F. Chen, University of Pittsburgh; Hui Mao, Emory University; Gao-Jun Teng, Southeast University, China
• Language: English
• Date: 2012-11-30
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Wang et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0050575
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 11
• Start Page: e50575
• End Page: e50575
• Grant/Funding Information: This work was supported by Major State Basic Research Development Program of China (973 Program, No. 2010CB933903) and National Nature Science Foundation of China (NSFC, No. 30830039, No. 81071125).
• Keywords: Liver transplantation; UMBILICAL-CORD BLOOD; Near-infrared spectroscopy; Multidisciplinary Sciences; PRECURSOR CELLS; MULTIDISCIPLINARY SCIENCES; PERIPHERAL-BLOOD; ANTIANGIOGENIC THERAPY; STEM-CELLS; GROWTH; ENZYME/PRODRUG CANCER-THERAPY; Relaxation time; In vivo imaging; Liver; Fluorescence imaging; ANGIOGENESIS; Magnetic resonance imaging; Fluorescence microscopy; CYTOSINE DEAMINASE; VASCULAR NORMALIZATION; Science & Technology; Science & Technology - Other Topics
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Radiology

Abstract

Objective: Bone-marrow derived endothelial progenitor cells (EPCs) play an important role in tumor neovasculature. Due to their tumor homing property, EPCs are regarded as promising targeted vectors for delivering therapeutic agents in cancer treatment. Consequently, non-invasive confirmation of targeted delivery via imaging is urgently needed. This study shows the development and application of a novel dual-modality probe for in vivo non-invasively tracking of the migration, homing and differentiation of EPCs. Methods: The paramagnetic/near-infrared fluorescence probe Conjugate 1 labeled EPCs were systemically transplanted into mice bearing human breast MDA-MB-231 tumor xenografts. Magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescence optical imaging were performed at different stages of tumor development. The homing of EPCs and the tumor neovascularization were further evaluated by immunofluorescence. Results: Conjugate 1 labeled EPCs can be monitored in vivo by MRI and NIR fluorescence optical imaging without altering tumor growth for up to three weeks after the systemic transplantation. Histopathological examination confirmed that EPCs were recruited into the tumor bed and then incorporated into new vessels two weeks after the transplantation. Tumor size and microvessel density was not influenced by EPCs transplantation in the first three weeks. Conclusions: This preclinical study shows the feasibility of using a MRI and NIR fluorescence optical imaging detectable probe to non-invasively monitor transplanted EPCs and also provides strong evidence that EPCs are involved in the development of endothelial cells during the tumor neovascularization.