title: Positron emission tomography imaging of tumors expressing the human chemokine receptor CXCR4 in mice with the use of 64Cu-AMD3100.
abstract: OBJECTIVE
  Expression of CXCR4 in cancers has been correlated with poor prognosis and increased metastasis. Quantifying CXCR4 expression non-invasively might aid in prognostication and monitoring therapy. We evaluated a radiolabeled antagonist of CXCR4, ⁶⁴Cu-AMD3100, as a positron-emitting imaging agent.
  
  
  METHODS
  CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of ⁶⁴Cu-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays.
  
  
  RESULTS
  ⁶⁴Cu-AMD3100 accumulated in CXCR4-expressing, but not CXCR4-negative, tumors. For CXCR4-expressing tumors, tumor-to-blood and tumor-to-muscle ratios were 23-41 and 50-59, respectively, depending on tumor type. Excess of unlabeled Cu-AMD3100 or AMD3100 significantly reduced ⁶⁴Cu-AMD3100 accumulation in CXCR4-expressing tumors. Human-absorbed dose calculations predicted a dose limit of 444 MBq.
  
  
  CONCLUSIONS
  CXCR4 can be imaged in tumors using ⁶⁴Cu-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that ⁶⁴Cu-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.
authors.affiliation: Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, 10 Center Drive, Room 11N111, Bethesda, MD 20892, USA.
authors.forename: Ido D
authors.initials: ID
authors.lastname: Weiss
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: John P
authors.initials: JP
authors.lastname: Jacobus
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Szajek
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
mesh_terms: D000818:Animals; D001596:Benzylamines; D016466:CHO Cells; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006224:Cricetinae; D003412:Cricetulus; D000080027:Cyclams; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D014018:Tissue Distribution; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D003301:Copper Radioisotopes; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019275:Radiopharmaceuticals; D019718:Receptors, CXCR4; C088327:plerixafor