title: 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.
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Srivastava
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Nidhi
authors.initials: N
authors.lastname: Chadha
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism; D002614:Chelating Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D015195:Drug Design; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D009928:Organ Specificity; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C586272:10-(2-aminoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-tris(methylenephosphonic acid); D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals
keywords: DOTMP; Diagnostic agent; Ga; PET; Phosphonate; SPECT; Tc