Synthesis and biological evaluation of a novel decadentate ligand DEPA

Bioorg Med Chem Lett. 2008 Nov 1;18(21):5792-5. doi: 10.1016/j.bmcl.2008.09.063. Epub 2008 Sep 19.

Abstract

An efficient and short synthetic route to a novel decadentate ligand 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-bis-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid (DEPA) with both macrocyclic and acyclic binding moieties is reported. A reproducible and scalable synthetic method to a precursor molecule of DEPA, 1,4,7-tris(tert-butoxycarbonylmethyl)tetraazacyclododecane was developed. DEPA was evaluated as a chelator of (177)Lu, (212)Bi, and (213)Bi for potential use in an antibody-targeted cancer therapy, radioimmunotherapy (RIT) using Arsenazo III based spectroscopic complexation kinetics, in vitro serum stability, and in vivo biodistribution studies.

Publication types

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

MeSH terms

  • Chelating Agents / chemical synthesis*
  • Chelating Agents / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / pharmacology
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Ligands
  • Reproducibility of Results

Substances

  • 7-(2-(bis-carboxymethyl-amino)ethyl)-4,10-bis-carboxymethyl-1,4,7,10-tetraazacyclododec-1-yl-acetic acid
  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Ligands
  • Glycine