title: Chemical and biological evaluation of 153Sm and 166Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H4 dotp OEt).
abstract: The novel methylphosphonic acid monoethylester (H(4)dotp(OEt)) has been synthesized and characterized and their complexes with Sm(III) and Ho(III) ions were studied. Dissociation constants of the ligand are lower than those of H(4)dota. The stability constants of the Ln(III)-H(4)dotp(OEt) complexes are surprisingly much lower that those of H(4)dota (H(4)dota=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) probably due to a lower coordination ability of the phosphonate monoester groups. Acid-assisted decomplexation studies have shown that both complexes are less kinetically inert than the H(4)dota complexes, but still much more inert than complexes of open-chain ligands. Nevertheless, the synthesis of (153)Sm and (166)Ho complexes with this ligand led to stable complexes both in vitro and in vivo. A very low binding of these complexes to hydroxyapatite (HA) and calcified tissues was observed confirming the assumption that a fully ionized phosphonate group(s) is necessary for a strong bone affinity. Both complexes show similar behaviour in vivo and, in general, follow the biodistribution trend of the H(4)dota complexes with the same metals.
authors: Department of Inorganic Chemistry, Faculty of Science, Universita Karlova (Charles University), Hlavova 2030, 128 40 Prague 2, Czech Republic.
authors: Michaela
authors: M
authors: Försterová
authors: Zuzana
authors: Z
authors: Jandurová
authors: Fernanda
authors: F
authors: Marques
authors: Lurdes
authors: L
authors: Gano
authors: Premysl
authors: P
authors: Lubal
authors: Jakub
authors: J
authors: Vanek
authors: Petr
authors: P
authors: Hermann
authors: Isabel
authors: I
authors: Santos
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D004355:Drug Stability; D004952:Esters / Q000737:chemistry / Q000493:pharmacokinetics; D006695:Holmium / Q000493:pharmacokinetics*; D006801:Humans; D008024:Ligands; D063065:Organophosphonates / Q000737:chemistry / Q000493:pharmacokinetics*; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012493:Samarium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D004952:Esters; D008024:Ligands; D063065:Organophosphonates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012493:Samarium; D006695:Holmium