Comparison of different phosphorus-containing ligands complexing ⁶⁸Ga for PET-imaging of bone metabolism

Abstract

Abstract 99m Tc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68 Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphorus-containing ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68 Ga in Na-HEPES buffer at pH∼4. Except for DOTP, all ligands were labelled with >92% yield. Binding of the 68 Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68 Ga-EDTMP and 68 Ga-DOTP was >83%. For the 68 Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than 68 Ga-DOTP and 68 Ga-EDTMP. μ-PET studies in vivo were performed with 68 Ga-EDTMP and 68 Ga-DOTP with Wistar rats. While 68 Ga-EDTMP-PET showed uptake on bone structures, an excess amount of the ligand (>1.5 mg EDTMP/kg body weight) had to be used, otherwise the 68 Ga 3+ is released from the complex and forms gallium hydroxide or it is transchelated to 68 Ga-transferrin. As a result, the main focus of further phosphonate structures has to be on complex formation in high radiochemical yields with macrocyclic ligands with phosphonate groups that are not required for complexing 68 Ga.