Positron emission tomography imaging of tumors expressing the human chemokine receptor CXCR4 in mice with the use of 64Cu-AMD3100

Mol Imaging Biol. 2012 Feb;14(1):106-14. doi: 10.1007/s11307-010-0466-y.


Purpose: 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.

Procedures: 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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CHO Cells
  • Carcinoma, Lewis Lung / diagnostic imaging
  • Carcinoma, Lewis Lung / metabolism
  • Cell Line, Tumor
  • Copper Radioisotopes* / chemistry
  • Copper Radioisotopes* / pharmacokinetics
  • Cricetinae
  • Cricetulus
  • Female
  • Heterocyclic Compounds* / chemistry
  • Heterocyclic Compounds* / pharmacokinetics
  • Humans
  • Liver Neoplasms, Experimental / diagnostic imaging
  • Liver Neoplasms, Experimental / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Imaging / methods
  • Neoplasms, Experimental / diagnostic imaging*
  • Neoplasms, Experimental / metabolism
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / metabolism
  • Positron-Emission Tomography / methods*
  • Radiation Dosage
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptors, CXCR4 / biosynthesis*
  • Receptors, CXCR4 / genetics
  • Tissue Distribution
  • Transfection
  • Transplantation, Heterologous


  • CXCR4 protein, human
  • Copper Radioisotopes
  • Heterocyclic Compounds
  • Radiopharmaceuticals
  • Receptors, CXCR4
  • plerixafor