title: Structural Characterization of Sm(III)(EDTMP).
abstract: Samarium-153 ethylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid) ((153)Sm-EDTMP, or samarium lexidronam), also known by its registered trademark name Quadramet, is an approved therapeutic radiopharmaceutical used in the palliative treatment of painful bone metastases. Typically, patients with prostate, breast, or lung cancer are most likely to go on to require bone pain palliation treatment due to bone metastases. Sm(EDTMP) is a bone-seeking drug which accumulates on rapidly growing bone, thereby delivering a highly region-specific dose of radiation, chiefly through β particle emission. Even with its widespread clinical use, the structure of Sm(EDTMP) has not yet been characterized at atomic resolution, despite attempts to crystallize the complex. Herein, we prepared a 1:1 complex of the cold (stable isotope) of Sm(EDTMP) under alkaline conditions and then isolated and characterized the complex using conventional spectroscopic techniques, as well as with extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional structure calculations, using natural abundance Sm. We present the atomic resolution structure of [Sm(III)(EDTMP)-8H](5-) for the first time, supported by the EXAFS data and complementary spectroscopic techniques, which demonstrate that the samarium coordination environment in solution is in agreement with the structure that has long been conjectured.
authors.affiliation: Pharmaceutical Orthopaedic Research Lab, 2-020J Katz Group Centre for Pharmacy & Health Research, Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta , Edmonton, Alberta, Canada T6G 2E1.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anatomy & Cell Biology, University of Saskatchewan , Saskatoon, Saskatchewan, Canada S7N 5E5.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pushie
authors.affiliation: Department of Anatomy & Cell Biology, University of Saskatchewan , Saskatoon, Saskatchewan, Canada S7N 5E5.
authors.forename: D M L
authors.initials: DM
authors.lastname: Cooper
authors.affiliation: Pharmaceutical Orthopaedic Research Lab, 2-020J Katz Group Centre for Pharmacy & Health Research, Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta , Edmonton, Alberta, Canada T6G 2E1.
authors.forename: M R
authors.initials: MR
authors.lastname: Doschak
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009942:Organometallic Compounds / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011789:Quantum Theory; D013050:Spectrometry, Fluorescence / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D056928:X-Ray Absorption Spectroscopy / Q000379:methods
chemical_list: D018712:Analgesics, Non-Narcotic; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C061972:samarium Sm-153 lexidronam
keywords: DFT; EXAFS; Quadramet; lexidronam; molecular dynamics; solvation