A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging

Bioorg Med Chem Lett. 2014 Mar 1;24(5):1386-8. doi: 10.1016/j.bmcl.2014.01.031. Epub 2014 Jan 21.

Abstract

We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.

Keywords: Bivalent effect; CXCR4; DOTA; Radiogallium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Gallium Radioisotopes / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Ligands
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / metabolism
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / metabolism*

Substances

  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Ligands
  • Peptides
  • Radiopharmaceuticals
  • Receptors, CXCR4
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid