Radiolabeling and evaluation of two 177Lu-labeled bis-phosphonates

Introduction: Bone pain palliation therapy is a mandate in handling end-stage cancer patients. The development of new ligands with higher stability, better pharmacokinetics and lower unwanted tissue uptakes (liver and GI) is still ongoing. Methods: In this work Lu-177 labeled (3-amino-1-hydroxypropane-1,1-di-yl)-bis-(phosphonate) (177Lu-pamidronate; 177Lu-PAM ), and (3-amino-1-hydroxybutane-1,1-di-yl)-bis-(phosphonate) (177Lu-alendronate; 177Lu-ALN)  complexes were prepared successfully using related ligands and 177LuCl3 at 25ºC & 60ºC at various ligand:metal ratios for 60-360 min. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 1013 n.cm-2s-1) of natural Lu2O3 samples. Radiochemical purities of 177Lu- complexes were checked by ITLC and HPLC. Stability studies of final preparation in the presence of human serum were evaluated along with protein binding studies as well as hydroxyapatite (HA) binding test. The biodistribution of 177Lu-complexes and 177LuCl3 in mice were determined for 7 d. Results: The complexes were obtained in high radiochemical purity ITLC (> 97%) and HPLC (> 99.9%). Satisfactory stability in presence of human serum and final formulations were obtained ( 90% in 48 h).HA binding assay demonstrated > 98% binding from 5-20 mg. The complex protein binding was about 50-58%. Conclusion: Biodistribution of both complexes demonstrated low bone uptake ratios at all time intervals, for far inferior to 177Lu-EDTMP.

Keywords:

Lu-177 , Pamidronate , Alendronate , Palliation therapy , Biodistribution , Pharmacokinetics