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 (64)Cu-AMD3100 with a specific activity of 11.28Ci/ micromol (417GBq/ micromol) 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. (64)Cu-AMD3100 binding affinity to CXCR4 was found to be 62.7 microM. Biodistribution of (64)Cu-AMD3100 showed accumulation in CXCR4-expressing organs and tissues, a renal clearance pathway, and an anomalous specific accumulation in the liver. We conclude that (64)Cu-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.