title: 64Cu-AMD3100--a novel imaging agent for targeting chemokine receptor CXCR4.
abstract: 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.
authors.affiliation: Positron Emission Tomography Radiochemistry Group, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD 20892, USA.
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Ido D
authors.initials: ID
authors.lastname: Weiss
authors.forename: Lawrence
authors.initials: L
authors.lastname: Szajek
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
mesh_terms: D000818:Animals; D001596:Benzylamines; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry*; D000080027:Cyclams; D003952:Diagnostic Imaging / Q000379:methods; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001596:Benzylamines; D003301:Copper Radioisotopes; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019275:Radiopharmaceuticals; D019718:Receptors, CXCR4; C088327:plerixafor