177Lu labelled polyaminophosphonates as potential agents for bone pain palliation

Polyphosphonate ligands labelled with radioisotopes decaying by moderate energy beta emission have shown utility as palliative agents for painful bone metastasis. Lu-177 (T-1/2 =6.71 d, E-beta max=497 keV) has radionuclidic properties suitable for use in palliative therapy of bone metastasis. Lu-177 was produced at a high specific activity and excellent radionuclidic purity by thermal neutron bombardment of a target prepared from natural Lu. Three polyaminomethylene phosphonate ligands, abbreviated as EDTMP, DTPMP and TTHMP, were synthesized and radiolabelled with Lu-177. Complexation parameters were optimized to achieve maximum yields (97-99.5%.). All the complexes were found to retain their stability at room temperature even 14 days after preparation. Biodistribution studies of the complexes were carried out in Wistar rats. All the complexes showed significant bone uptake (6-6.5%/g in tibia at 3 h post-injection (p.i.)) with rapid clearance from blood and minimum uptake in soft tissues. These studies reveal that Lu-177 complexes with the synthesized ligands have a potential use in palliative treatment of painful bone metastasis. ((C) 2002 Lippincott Williams & Wilkins).