Synthesis and in vitro evaluation of 68Ga-DOTA-4-FBn-TN14003, a novel tracer for the imaging of CXCR4 expression

Bioorg Med Chem. 2012 Feb 15;20(4):1502-10. doi: 10.1016/j.bmc.2011.12.052. Epub 2012 Jan 2.


The expression of the chemokine receptor CXCR4 in tumors is associated with tumor aggressiveness and poor prognosis for the patient and contributes to metastatic seeding. Therefore it is of high interest to find a specific PET tracer for the imaging of CXCR4 expression in tumors. The aim of this study was the synthesis, (68)Ga labeling and first evaluation of DOTA-4-FBn-TN14003 as a potential PET tracer for this purpose. DOTA-4-FBn-TN14003 was synthesized using solid phase peptide synthesis and radiolabeling of this versatile precursor was performed with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator. (68)Ga-DOTA-4-FBn-TN14003 was reproducibly obtained in isolated radiochemical yields of 72.5±4.9% with an excellent radiochemical purity of >99.5%. Specific activities of up to 29.8±3.1 GBq/μmol were achieved. In competition binding assays with SDF-1α, human T cell lymphoma Jurkat cells expressed high levels of CXCR4 whereas human breast cancer MDA-MB-231 cells expressed significantly lower levels of this chemokine receptor. The inhibition constants (IC(50)) of Ga-DOTA-4-FBn-TN14003 and 4-FBn-TN14003 to CXCR4 were determined in a competition assay against (125)I-SDF-1α using Jurkat as well as MDA-MB-231 cells. The IC(50) values of Ga-DOTA-4-FBn-TN14003 (1.99±0.31 nM) and 4-FBn-TN14003 (4.07±1.00 nM) proved to be comparable, indicating negligible influence of the metal complex. These results suggest (68)Ga-DOTA-4-FBn-TN14003 as a promising agent for the imaging of CXCR4 expression in tumors and metastases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Drug Stability
  • Gene Expression
  • Humans
  • Molecular Structure
  • Neoplasms / diagnosis*
  • Neoplasms / metabolism
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Radiopharmaceuticals
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*


  • 68Ga-DOTA-4-FBn-TN14003
  • Organometallic Compounds
  • Peptides
  • Radiopharmaceuticals
  • Receptors, CXCR4
  • TN14003