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

摘要

~(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 pH4. 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)GaNOTA-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 macro-cyclic ligands with phosphonate groups that are not required for complexing ~(68)Ga.