Detection of leukotriene receptor CysLT1R in inflammatory diseases by molecular imaging with near-infrared fluorescence-based contrast agents

Mol Imaging. 2011 Apr;10(2):81-90.

Abstract

As leukotriene D4 receptor CysLT1R upregulation is an early event in inflammatory processes, specific detection of CysLT1R via molecular imaging might be a promising diagnostic tool for inflammatory diseases. We coupled a specific anti-CysLT1R IgG antibody to near-infrared (NIR) hemicyanine fluorophore DY-734. The fluorophore was also coupled to unspecific rabbit-IgG antibody or corresponding Fab fragments. Expression of CysLT1R in HL-60 human promyelocytic leukemia cells in vitro could be proven by reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, and flow cytometry. Detection of the probes by flow cytometry showed that CysLT1R*DY-734 probe binds distinctly stronger to HL-60 cells than IgG*DY-734. Induction of ear edema in mice was conducted to test signaling of the synthesized probes in vivo. A markedly higher fluorescence intensity was observed in the edematous region than in the healthy region by a whole-body imaging system. Semiquantitative analysis showed that CysLT1R*DY-734 and Fab-CysLT1R*DY-734 probes bind 1.9- and 1.2-fold stronger, respectively, than the unspecific probes. Biodistribution studies revealed an enrichment of full-length IgG probes in liver and spleen, whereas Fab-containing probes are mostly found in liver and kidneys. Taken together, we present an approach that might improve early diagnosis of inflammatory diseases in the long term.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media*
  • Edema / metabolism*
  • Edema / pathology
  • Fluorescence
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism
  • HL-60 Cells
  • Humans
  • Immunoglobulin G / immunology
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Infrared Rays*
  • Male
  • Mice
  • Molecular Imaging / methods*
  • Rabbits
  • Receptors, Leukotriene / metabolism*
  • Tissue Distribution

Substances

  • Contrast Media
  • Fluorescent Dyes
  • Immunoglobulin G
  • Receptors, Leukotriene
  • leukotriene D4 receptor