177Lu-DOTMP: A viable agent for palliative radiotherapy of painful bone metastasis

Abstract

The suitable nuclear decay characteristics [T 1/2=6.73 d, E β (max)=497 keV, E γ=113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production with adequate specific activity and radionuclidic purity using a moderate flux reactor are important attributes towards 177Lu to be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study describes the preparation of 177Lu complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and its preliminary biological evaluation in animal models with an aim to proposing it as a viable radiopharmaceutical for bone pain palliation. The choice DOTMP as the polyaminophosphonic acid carrier ligand is based on the enhanced thermodynamic stability and kinetic inertness of the metal-ligand complexes with macrocyclic chelators. 177Lu was produced with a specific activity of ∼12 GBq/mg (∼324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu2O3 target at a thermal neutron flux of ∼6×1013 n/cm2s for 21 d. 177Lu-DOTMP complex was prepared in high yield and excellent radiochemical purity (>99%) using DOTMP synthesized and characterized in-house. The complex exhibited excellent in-vitro stability at room temperature. Biodistribution studies in Wistar rats showed rapid skeletal accumulation of the injected activity [(1.60±0.19) per gram in femur at 3 h post-injection] with fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic studies carried out in normal Wistar rats and New Zealand white rabbits also demonstrated significant accumulation of the agent in skeleton and almost no retention in any other vital organs.