title: 153Sm and 166Ho complexes with tetraaza macrocycles containing pyridine and methylcarboxylate or methylphosphonate pendant arms.
abstract: A set of tetraaza macrocycles containing pyridine and methylcarboxylate (ac(3)py14) or methylphosphonate (MeP(2)py14 and P(3)py14) pendant arms were prepared and their stability constants with La(3+), Sm(3+), Gd(3+) and Ho(3+) determined by potentiometry at 25 degrees C and 0.10 M ionic strength in NMe(4)NO(3). The metal:ligand ratio for (153)Sm and (166)Ho and for ac(3)py14, MeP(2)py14 and P(3)py14, as well as the pH of the reaction mixtures, were optimized to achieve a chelation efficiency higher than 98%. These radiocomplexes are hydrophilic and have a significant plasmatic protein binding. In vitro stability was studied in physiological solutions and in human serum. All complexes are stable in saline and PBS, but 20% of radiochemical impurities were detected after 24 h of incubation in serum. Biodistribution studies in mice indicated a slow rate of clearance from blood and muscle, a high and rapid liver uptake and a very slow rate of total radioactivity excretion. Some bone uptake was observed for complexes with MeP(2)py14 and P(3)py14, which was enhanced with time and the number of methylphosphonate groups. This biological profile supports the in vitro instability found in serum and is consistent with the thermodynamic stability constants found for these complexes.
authors.affiliation: Instituto Tecnológico e Nuclear, Estrada Nacional 10, 2686-953 Sacavém, Portugal. fmarujo@itn.mces.pt
authors.forename: Fernanda
authors.initials: F
authors.lastname: Marques
authors.forename: Krassimira P
authors.initials: KP
authors.lastname: Guerra
authors.forename: Lurdes
authors.initials: L
authors.lastname: Gano
authors.forename: Judite
authors.initials: J
authors.lastname: Costa
authors.forename: M Paula
authors.initials: MP
authors.lastname: Campello
authors.forename: Luís M P
authors.initials: LM
authors.lastname: Lima
authors.forename: Rita
authors.initials: R
authors.lastname: Delgado
authors.forename: Isabel
authors.initials: I
authors.lastname: Santos
mesh_terms: D001798:Blood Proteins / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D006695:Holmium / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000737:chemistry*; D011522:Protons; D011725:Pyridines / Q000737:chemistry*; D012493:Samarium / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D002264:Carboxylic Acids; D008024:Ligands; D009943:Organophosphorus Compounds; D011522:Protons; D011725:Pyridines; C032627:methylphosphonic acid; D012493:Samarium; C023666:pyridine; D006695:Holmium