In vivo imaging of ligand receptor binding with Gaussia luciferase complementation

Nat Med. 2011 Dec 4;18(1):172-7. doi: 10.1038/nm.2590.


Studies of ligand-receptor binding and the development of receptor antagonists would benefit greatly from imaging techniques that translate directly from cell-based assays to living animals. We used Gaussia luciferase protein fragment complementation to quantify the binding of chemokine (C-X-C motif) ligand 12 (CXCL12) to chemokine (C-X-C motif) receptor 4 (CXCR4) and CXCR7. Studies established that small-molecule inhibitors of CXCR4 or CXCR7 specifically blocked CXCL12 binding in cell-based assays and revealed differences in kinetics of inhibiting chemokine binding to each receptor. Bioluminescence imaging showed CXCL12-CXCR7 binding in primary and metastatic tumors in a mouse model of breast cancer. We used this imaging technique to quantify drug-mediated inhibition of CXCL12-CXCR4 binding in living mice. We expect this imaging technology to advance research in areas such as ligand-receptor interactions and the development of new therapeutic agents in cell-based assays and small animals.

Publication types

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

MeSH terms

  • Animals
  • Benzylamines
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Chemokine CXCL12 / analysis*
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / metabolism
  • Cyclams
  • Female
  • HEK293 Cells
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Ligands
  • Luciferases / analysis
  • Luciferases / metabolism*
  • Luminescent Measurements / methods*
  • Mice
  • Molecular Imaging / methods*
  • Neoplasms, Experimental / metabolism
  • Protein Binding / drug effects
  • Receptors, CXCR / analysis*
  • Receptors, CXCR / antagonists & inhibitors
  • Receptors, CXCR / metabolism
  • Receptors, CXCR4 / analysis*
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism


  • Benzylamines
  • Chemokine CXCL12
  • Cyclams
  • Heterocyclic Compounds
  • Ligands
  • Receptors, CXCR
  • Receptors, CXCR4
  • Luciferases
  • plerixafor