Preparation and biological evaluation of 153Sm-DOTMP as a potential agent for bone pain palliation

Abstract

Designing ideal radiopharmaceuticals for use as bone pain palliative agents requires the use of a moderate energy beta emitter as the radionuclide and a polyaminophosphonic acid as the carrier molecule. Cyclic polyaminophosphonic acid ligands are known for endowing higher thermodynamic stability and kinetic inertness of the radiolabelled agent when complexed with radiolanthanides. To use Sm (T1/2=46.27 h, Ebeta,max=0.81 MeV, Egamma=103 keV) as the radioisotope, obtainable at an adequate specific activity and high radionuclidic purity by irradiation of a natural Sm2O3 target, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) as the carrier ligand. The radiolabelling yields under optimized conditions were near quantitative with the additional merit of using a relatively low ligand:metal ratio of 2:1 unlike the 250-fold excess of ligands used in the case of the established agent, Sm-EDTMP. Radiochemical purity was retained with insignificant dissociation on storage up to 10 d at room temperature. Biodistribution studies in Wistar rats demonstrated selective skeletal uptake (4.52%+/-0.49% of injected activity per gram in tibia at 30 min post-injection) with rapid blood clearance and minimal uptake in any of the major organs. No leaching of skeletal activity was observed up to 48 h post-injection. Scintigraphic studies carried out in rabbits also showed significant skeletal accumulation and almost no retention of activity in other vital organs/tissues.