Improvement of CXCR4 tracer specificity for PET imaging

J Control Release. 2012 Jan 30;157(2):216-23. doi: 10.1016/j.jconrel.2011.09.076. Epub 2011 Sep 22.


Tumors expressing the chemokine receptor CXCR4 have been reported to be more aggressive and to produce more metastatic seeding in specific organs, such as the bone marrow. However, evaluation of tumors for CXCR4 expression requires testing of ex vivo biopsy samples, and is not routinely done in cancer management. In prior work to address this issue, we and others have developed tracers for positron emission tomography (PET) that targeted CXCR4, but in addition to binding to CXCR4 these tracers also bound to red blood cells (and to other unrelated targets) in vivo. Here we report two new tracers based on the CXCR4 peptide antagonist 4F-benzoyl-TN14003 (T140) that bind to CXCR4, but not to undesired targets. These tracers, NOTA-NFB and DOTA-NFB, show slight reductions in both 1) binding affinities for CXCR4 and 2) inhibition of CXCL12 induced migration, compared to T140, in vitro. Both NOTA-NFB and DOTA-NFB specifically accumulate in CXCR4-positive, but not CXCR4-negative, tumor xenografts in mice and allow clear visualization of CXCR4 expression by PET. Evaluation of NOTA-NFB and DOTA-NFB for their potential to mobilize immune cells and progenitor cells from the bone marrow to the peripheral blood revealed slightly reduced, but still comparable, results to the parent molecule T140. The tracers reported here may allow the evaluation of CXCR4 expression in primary tumors and metastatic nodules, and enable better informed, more personalized treatment for patients with cancer.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • CHO Cells
  • Chemokine CXCL12 / metabolism
  • Cricetinae
  • Cricetulus
  • Hematopoietic Stem Cell Mobilization
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / metabolism
  • Organometallic Compounds / pharmacology*
  • Peptides / pharmacology*
  • Positron-Emission Tomography / methods*
  • Radioactive Tracers*
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism*


  • 4-fluorobenzoyl-TN-14003
  • Biomarkers, Tumor
  • Chemokine CXCL12
  • Organometallic Compounds
  • Peptides
  • Radioactive Tracers
  • Receptors, CXCR4