The influence of chemical structure of phosphonic acids labeled with gallium-68 on their pharmacokinetic properties in animals

Abstract

Abstract 68 Ga-labeled phosphonates are of great interest due to their possibility to serve promising agents in nuclear medicine for bone tissue PET imaging. It is known that multidentate aminophosphonate ligands could form much stable chelates with different radiometals as compared to diphosphonates. In this work we studied the pharmacokinetic properties of 68Ga-labeled complexes with two, four and five phosphonate groups (68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP, respectively) in normal Wistar rats after intravenous administration. It was shown that the structure of phosphonates had a great influence on the biodistribution of 68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP. Complexes with higher number of aminomethylenephosphonate groups (68Ga-EDTMP and 68Ga-DTPMP) had higher bone uptake than diphosphonate 68Ga-HEDP. In blood 68Ga-HEDP had lower activity than 68Ga-EDTMP and 68Ga-DTPMP, indicating poor stability of diphosphonate-based complex. In other soft organs and tissues 68Ga-EDTMP and 68Ga-DTPMP uptake was slightly lower as compared with 68Ga-HEDP. In conclusion, 68Ga-EDTMP and 68Ga-DTPMP have the potential to be suitable radiotracers for bone tissue PET imaging.