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.
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.
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.
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.
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This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases and the National Institute of Biomedical Imaging and Bioengineering. We wish to thank Dr. David McDermott from NIAID, NIH, for providing reagents and advice.
Conflict of Interest Statement
The authors declare that they have no conflict of interest.
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Weiss, I.D., Jacobson, O., Kiesewetter, D.O. et al. Positron Emission Tomography Imaging of Tumors Expressing the Human Chemokine Receptor CXCR4 in Mice with the Use of 64Cu-AMD3100. Mol Imaging Biol 14, 106–114 (2012) doi:10.1007/s11307-010-0466-y