Synthesis, stabilization and formulation of [177Lu]Lu-AMBA, a systemic radiotherapeutic agent for Gastrin Releasing Peptide receptor positive tumors

Appl Radiat Isot. 2008 Apr;66(4):497-505. doi: 10.1016/j.apradiso.2007.11.007. Epub 2007 Nov 19.

Abstract

A robust formulation was developed for [(177)Lu]Lu-AMBA ((177)Lu-DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)), a Bombesin-like agonist with high affinity for Gastrin Releasing Peptide (GRP) receptors. During optimization of labeling, the effect of several radiostabilizers was evaluated; a combination of selenomethionine and ascorbic acid showed superiority over other tested radiostabilizers. The resulting two-vial formulation maintains a radiochemical purity (RCP) of >90% for at least 2 days at room temperature. The method of stabilization should be useful for other methionine-containing peptide radiopharmaceuticals in diagnostic and therapeutic applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Stability
  • Freezing
  • Humans
  • Hydrogen-Ion Concentration
  • Ligands
  • Lutetium / chemistry*
  • Lutetium / therapeutic use
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / therapeutic use
  • Radiation-Protective Agents / chemistry
  • Radioisotopes / chemistry*
  • Radioisotopes / therapeutic use
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / therapeutic use
  • Receptors, Bombesin
  • Reducing Agents / chemistry
  • Selenomethionine / chemistry

Substances

  • DO3A-CH2CO-G-4-aminobenzoyl-Q-W-A-V-G-H-L-M-NH2
  • Ligands
  • Oligopeptides
  • Radiation-Protective Agents
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Reducing Agents
  • Lutetium
  • Selenomethionine