Isolation of a 177Hf complex formed by beta-decay of a 177Lu-labeled radiotherapeutic compound and NMR structural elucidation of the ligand and its Lu and Hf complexes

Inorg Chem. 2009 Apr 6;48(7):3114-24. doi: 10.1021/ic802328a.

Abstract

(177)Lu-AMBA (AMBA = DO3A-CH(2)CO-G-[4-aminobenzoyl]-QWAVGHLM-NH(2)) is being developed for the radiotherapeutic treatment of tumors that express the gastrin-releasing peptide receptor (GRP-R). In this study we investigated the fate of the (177)hafnium ((177)Hf) that forms upon the decay of (177)Lu while the latter is complexed with AMBA. When decayed solutions of (177)Lu-AMBA were analyzed, it was found that (177)Hf is retained in the DO3A monoamide chelator, forming a pair of interconverting isomers. We report the synthesis and full characterization of (nat)Lu-AMBA and the studies performed to demonstrate its correspondence to radioactive (177)Lu-AMBA. We also report the synthesis and characterization of Hf-AMBA and, by NMR studies, show structural analogies between Hf-AMBA, its parent compound Lu-AMBA, and the unmetallated AMBA ligand. In the NMR spectra of both the metallated and unmetallated AMBA ligand, a stacking interaction between the amino benzoyl residue in the linker and a tryptophan in the truncated bombesin [BBN(7-14)-NH(2)] peptide targeting group was found.

MeSH terms

  • Crystallography, X-Ray
  • Hafnium / chemistry*
  • Isotopes / chemistry
  • Ligands
  • Lutetium / chemistry*
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*

Substances

  • Isotopes
  • Ligands
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Lutetium
  • Hafnium