JBIC Journal of Biological Inorganic Chemistry

, Volume 9, Issue 7, pp 859–872 | Cite as

153Sm and 166Ho complexes with tetraaza macrocycles containing pyridine and methylcarboxylate or methylphosphonate pendant arms

  • Fernanda Marques
  • Krassimira P. Guerra
  • Lurdes Gano
  • Judite Costa
  • M. Paula Campello
  • Luís M. P. Lima
  • Rita Delgado
  • Isabel Santos
Original Article

Abstract

A set of tetraaza macrocycles containing pyridine and methylcarboxylate (ac3py14) or methylphosphonate (MeP2py14 and P3py14) pendant arms were prepared and their stability constants with La3+, Sm3+, Gd3+ and Ho3+ determined by potentiometry at 25 °C and 0.10 M ionic strength in NMe4NO3. The metal:ligand ratio for 153Sm and 166Ho and for ac3py14, MeP2py14 and P3py14, 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 MeP2py14 and P3py14, 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.

Keywords

Lanthanides Pendant arms Radiopharmaceuticals Stability constants Tetraaza macrocycles 

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Copyright information

© SBIC 2004

Authors and Affiliations

  • Fernanda Marques
    • 1
  • Krassimira P. Guerra
    • 2
  • Lurdes Gano
    • 1
  • Judite Costa
    • 2
    • 3
  • M. Paula Campello
    • 1
  • Luís M. P. Lima
    • 2
  • Rita Delgado
    • 2
    • 4
  • Isabel Santos
    • 1
  1. 1.Instituto Tecnológico e NuclearSacavémPortugal
  2. 2.Instituto de Tecnologia Química e BiológicaUNLOeirasPortugal
  3. 3.Faculdade de FarmáciaUniversidade de LisboaLisbonPortugal
  4. 4.Instituto Superior TécnicoLisbonPortugal

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