175Yb labeled polyaminophosphonates as potential agents for bone pain palliation

Abstract

Ytterbium-175 ( T 1/2=4.2 d, E β(max) =480 keV) has radionuclidic properties suitable to be used in palliative therapy of bone metastases. 175Yb can be produced in moderate specific activity and good radionuclidic purity by thermal neutron bombardment of natural Yb target. The analysis of the neutron irradiated sample exhibited the presence of 96.2% 175Yb along with 2.1% 169Yb and 1.7% 177Lu at 6 h post-EOB. Four polyaminomethylene phosphonic acid ligands, ethylenediamine tetramethylene phosphonic acid, propylenediamine tetramethylene phosphonic acid, triethylenetetramine hexamethylene phosphonic acid and diethylenetriamine pentamethylene phosphonic acid were synthesized and radiolabeled with 175Yb. Complexation parameters were optimized to achieve maximum yields (92–99%). All complexes were found to retain their stability at room temperature even after 10 d of preparation. Biodistribution studies of the complexes carried out in Wistar rats showed significant bone uptake (3–4.4%/g in tibia at 3 h post-injection) with rapid clearance from blood and minimum uptake in soft tissues for all the complexes (bone/blood ratio ∼40–150 and bone/muscles ratio ∼40–400 at 3 h post-injection). These studies suggest that 175Yb complexes with the phosphonate ligands have potential for use in palliative treatment of painful bone metastases.