title: Non-invasive imaging of endothelial progenitor cells in tumor neovascularization using a novel dual-modality paramagnetic/near-infrared fluorescence probe.
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.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Wang
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Xin-Gui
authors.initials: XG
authors.lastname: Peng
authors.forename: Alex F
authors.initials: AF
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Gao-Jun
authors.initials: GJ
authors.lastname: Teng
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000166:cytology; D002232:Carbocyanines / Q000737:chemistry; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007259:Infrared Rays; D008279:Magnetic Resonance Imaging / Q000379:methods*; D059346:Magnets; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D051379:Mice; D009389:Neovascularization, Pathologic; D061848:Optical Imaging / Q000379:methods*; D051381:Rats; D013194:Staining and Labeling; D033581:Stem Cell Transplantation
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D005682:Gadolinium