64Cu-AMD3100-A novel imaging agent for targeting chemokine receptor CXCR4

CXCR4 is a chemokine receptor which has been shown to be exploited by various tumors for increased survival, invasion, and homing to target organs. We developed a one step radiosynthesis for labeling the CXCR4-specific antagonist AMD3100 with Cu-64 to produce Cu-64-AMD3100 with a specific activity of 11.28 Ci/mu mol (417 GBq/mu mol) at the end of radiosynthesis. Incorporation of Cu(II) ion into AMD3100 did not change its ability to inhibit cellular migration in response to the (only) CXCR4 ligand, SDF-1/CXCL12. Cu-64-AMD3100 binding affinity to CXCR4 was found to be 62.7 mu M. Biodistribution of Cu-64-AMD3100 showed accumulation in CXCR4-expressing organs and tissues, a renal clearance pathway, and an anomalous specific accumulation in the liver. We conclude that Cu-64-AMD3100 exhibits promise as a potential PET imaging agent for visualization of CXCR4-positive tumors and metastases and might be used to guide and monitor anti-CXCR4 tumor therapy. (c) Published by Elsevier Ltd.