13- and 14-membered macrocyclic ligands containing methylcarboxylate or methylphosphonate pendant arms: Chemical and biological evaluation of their ¹⁵³Sm and ¹⁶⁶Ho complexes as p

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• 作者：Fernanda Marques ; Lurdes Gano ; M. Paula Campello ; Sara Lacerda ; Isabel Santos ; Luí ; s M.P. Lima ; Judite Costa ; Patrí ; cia Antunes and Rita Delgado
• 关键词：Lanthanides ; Macrocycles ; Biological studies ; Radiopharmacy
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2006
• 期刊代码：53_01620134
• 类别：ch
• 出版时间：February 2006
• 卷：100
• 期：2
• 页码：270-280
• 文件大小：389 K

摘要

The stability constants of La³⁺, Sm³⁺ and Ho³⁺ complexes with 13- and 14-membered macrocycles having methylcarboxylate (trita and teta) or methylphosphonate (tritp and tetp) arms were determined. All the ligands were labelled with ¹⁵³Sm and ¹⁶⁶Ho in order to evaluate the effect of the macrocyclic cavity size and type of appended arms on their in vitro and in vivo behaviour. The radiolabelling efficiency was found to be higher than 98%for all the complexes, except for those of tetp. All radiocomplexes studied are hydrophilic with an overall negative charge and low plasmatic protein binding. Good in vitro stability in physiological media and human serum was found for all complexes, except the ¹⁵³Sm/¹⁶⁶Ho–teta, which are unstable in phosphate buffer (pH 7.4). In vitro hydroxyapatite (HA) adsorption studies indicated that ¹⁵³Sm/¹⁶⁶Ho–tritp complexes bind to HA having the ¹⁶⁶Ho complex the highest degree of adsorption (>80%, 10 mg). Biodistribution studies in mice demonstrated that ¹⁵³Sm/¹⁶⁶Ho–trita complexes have a fast tissue clearance with more than 95%of the injected activity excreted after 2 h, value that is comparable to the corresponding dota complexes. In contrast, the ¹⁵³Sm–teta complex has a significantly lower total excretion. ¹⁵³Sm/¹⁶⁶Ho–tritp complexes are retained by the bone, particularly ¹⁶⁶Ho–tritp that has 5–6%(%I.D./g) bone uptake and also a high rate of total excretion. Thus, these studies support the potential interest of ¹⁵³Sm/¹⁶⁶Ho–trita complexes for therapy when conjugated to a biomolecule and the potential usefulness of the ¹⁶⁶Ho–tritp complex in bone pain palliation.