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

In vivo imaging of ligand receptor binding with Gaussia luciferase complementation.

Author information

1
Center for Molecular Imaging, Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Abstract

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.

PMID:
22138753
PMCID:
PMC3253890
DOI:
10.1038/nm.2590
[Indexed for MEDLINE]
Free PMC Article

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