Targeting of alpha(nu)beta(3)-integrins expressed on tumor tissue and neovasculature using fluorescent small molecules and nanoparticles

Nanomedicine (Lond). 2010 Jul;5(5):715-26. doi: 10.2217/nnm.10.38.


Aim: 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.

Materials & 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms / diagnosis
  • Contrast Media / chemistry
  • Female
  • Fluorescent Dyes* / chemistry
  • Fluorocarbons* / chemistry
  • Humans
  • Indoles* / chemistry
  • Integrin alphaVbeta3 / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles* / chemistry
  • Neoplasms / diagnosis*
  • Neovascularization, Pathologic / diagnosis*
  • Peptides* / chemistry
  • Peptides, Cyclic* / chemistry
  • Spectroscopy, Near-Infrared / methods
  • Whole-Body Counting


  • Contrast Media
  • Fluorescent Dyes
  • Fluorocarbons
  • Indoles
  • Integrin alphaVbeta3
  • Peptides
  • Peptides, Cyclic
  • cypate-cyclic(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)