In Vivo Imaging of Ligand Receptor Binding with Gaussia Luciferase Complementation

Studies of ligand-receptor binding and 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 binding of chemokine CXCL12 to receptors CXCR4 and CXCR7. Small molecule inhibitors of CXCR4 or CXCR7 specifically blocked CXCL12 binding in cell-based assays, and these studies revealed differences in kinetics for 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 also 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 including ligand-receptor interactions and development of new therapeutic agents in cell-based assays and small animals.