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

Tc-99m-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different Ga-68-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using mu-PET. Seven macrocyclic phosphorus-containing ligands and EDTMP were labelled in nanomolar scale with n.c.a. Ga-68 in Na-HEPES buffer at pH similar to 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the Ga-68-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of Ga-68-EDTMP and Ga-68-DOTP was > 83%. For the Ga-68-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than Ga-68-DOTP and Ga-68-EDTMP. mu-PET studies in vivo were performed with Ga-68-EDTMP and Ga-68-DOTP with Wistar rats. While Ga-68-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 Ga-68(3+) a is released from the complex and forms gallium hydroxide or it is transchelated to Ga-68-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 Ga-68.