Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors

Nucl Med Biol. 2006 May;33(4):489-94. doi: 10.1016/j.nucmedbio.2006.01.006. Epub 2006 May 2.


The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For 111In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of d-Lys(8) which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more 111In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that 111In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Drug Delivery Systems / methods
  • Drug Design
  • Female
  • Isotope Labeling / methods
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Proteins / metabolism*
  • Organ Specificity
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / metabolism*
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacokinetics
  • Peptides / chemical synthesis
  • Peptides / pharmacokinetics
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacokinetics*
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Chemokine / metabolism
  • Tissue Distribution


  • 111indium-DTPA-Ac-TZ14011
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Peptides
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • Receptors, Chemokine
  • Pentetic Acid