Synthesis and biological evaluation of newly designed phosphonate based bone-seeking agent.

Abstract A cyclic tetraaza based bifunctional triphosphonate ligand 10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(methylenephosphonic acid) (DO3MP-EA) was synthesized as bone-seeking theranostic agent. The compound was characterized by spectroscopic techniques and labelled with 99m Tc with more than 97% purity. Blood clearance of 99mTc labelled compound a quick wash out from the circulation. The compound was excreted mainly via kidneys and accumulation of 99m Tc-DO3MP-EA in bone was 9.53 ± 1.06% of injected dose per gram of bone at 1 h. The preliminary CADD analysis confirms the efficacy of DO3MP-EA (G Score −7.005) as better binding agent for osteocalcin (pdb 1Q8H) rather than other known clinical agents. Subsequently stability constant of chelate with Ga(III) was found to be 18.6 which confirms its efficacy as 68 Ga labelled PET radiopharmaceutical for bone.