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

^99mTc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different ⁶⁸Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphoruscontaining ligands and EDTMP were labelled in nanomolar scale with n.c.a. ⁶⁸Ga in Na-HEPES buffer at pH ∼ 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the ⁶⁸Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of ⁶⁸Ga-EDTMP and ⁶⁸Ga-DOTP was > 83%. For the ⁶⁸Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than ⁶⁸Ga-DOTP and ⁶⁸Ga-EDTMP. μ-PET studies in vivo were performed with ⁶⁸Ga-EDTMP and ⁶⁸Ga-DOTP with Wistar rats. While ⁶⁸Ga-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 ⁶⁸Ga³⁺ is released from the complex and forms gallium hydroxide or it is transchelated to ⁶⁸Ga-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 ⁶⁸Ga.