Targeted zwitterionic near-infrared fluorophores for improved optical imaging

Nat Biotechnol. 2013 Feb;31(2):148-53. doi: 10.1038/nbt.2468. Epub 2013 Jan 6.


The signal-to-background ratio (SBR) is the key determinant of sensitivity, detectability and linearity in optical imaging. As signal strength is often constrained by fundamental limits, background reduction becomes an important approach for improving the SBR. We recently reported that a zwitterionic near-infrared (NIR) fluorophore, ZW800-1, exhibits low background. Here we show that this fluorophore provides a much-improved SBR when targeted to cancer cells or proteins by conjugation with a cyclic RGD peptide, fibrinogen or antibodies. ZW800-1 outperforms the commercially available NIR fluorophores IRDye800-CW and Cy5.5 in vitro for immunocytometry, histopathology and immunoblotting and in vivo for image-guided surgery. In tumor model systems, a tumor-to-background ratio of 17.2 is achieved at 4 h after injection of ZW800-1 conjugated to cRGD compared to ratios of 5.1 with IRDye800-CW and 2.7 with Cy5.5. Our results suggest that introducing zwitterionic properties into targeted fluorophores may be a general strategy for improving the SBR in diagnostic and therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / isolation & purification
  • Cell Line, Tumor
  • Fibrinogen / isolation & purification
  • Fluorescent Dyes / chemistry
  • Humans
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Neoplasms / diagnosis
  • Neoplasms / pathology*
  • Optical Imaging / methods*
  • Peptides, Cyclic / isolation & purification
  • Quaternary Ammonium Compounds* / chemistry
  • Signal-To-Noise Ratio
  • Sulfonic Acids* / chemistry
  • Surgery, Computer-Assisted


  • Antibodies
  • Fluorescent Dyes
  • Peptides, Cyclic
  • Quaternary Ammonium Compounds
  • Sulfonic Acids
  • ZW800-1 compound
  • cyclic arginine-glycine-aspartic acid peptide
  • Fibrinogen