title: Targeting of alpha(nu)beta(3)-integrins expressed on tumor tissue and neovasculature using fluorescent small molecules and nanoparticles.
abstract: OBJECTIVE
  Receptor-specific small molecules and nanoparticles are widely used in molecular imaging of tumors. Although some studies have described the relative strengths and weaknesses of the two approaches, reports of a direct comparison and analysis of the two strategies are lacking. Herein, we compared the tumor-targeting characteristics of a small near-infrared fluorescent compound (cypate-peptide conjugate) and relatively large perfluorocarbon-based nanoparticles (250 nm diameter) for imaging alpha(nu)beta(3)-integrin receptor expression in tumors.
  
  
  METHODS
  Near-infrared fluorescent small molecules and nanoparticles were administered to living mice bearing subcutaneous or intradermal syngeneic tumors and imaged with whole-body and high-resolution optical imaging systems.
  
  
  RESULTS
  The nanoparticles, designed for vascular constraint, remained within the tumor vasculature while the small integrin-avid ligands diffused into the tissue to target integrin expression on tumor and endothelial cells. Targeted small-molecule and nanoparticle contrast agents preferentially accumulated in tumor tissue with tumor-to-muscle ratios of 8 and 7, respectively, compared with 3 for nontargeted nanoparticles.
  
  
  CONCLUSIONS
  Fluorescent small molecular probes demonstrate greater overall early tumor contrast and rapid visualization of tumors, but the vascular-constrained nanoparticles are more selective for detecting cancer-induced angiogenesis. A combination of both imaging agents provides a strategy to image and quantify integrin expression in tumor tissue and tumor-induced neovascular systems.
authors.affiliation: Department of Radiology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Akers
authors.forename: Zongren
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mikhail
authors.initials: M
authors.lastname: Berezin
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Ye
authors.forename: Anthony
authors.initials: A
authors.lastname: Agee
authors.forename: Kevin
authors.initials: K
authors.lastname: Guo
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Fuhrhop
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Wickline
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lanza
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000175:diagnosis*; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014915:Whole-Body Counting
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D005466:Fluorocarbons; D007211:Indoles; D039302:Integrin alphaVbeta3; D010455:Peptides; D010456:Peptides, Cyclic; C553662:cypate-cyclic(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)