Chemical and biological evaluation of ¹⁵³Sm and ¹⁶⁶Ho complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid monoethylester) (H₄dotp^O

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• 作者：Michaela Fö ; rsterová ; Zuzana J ; urová ; Fern ; a Marques ; Lurdes Gano ; Př ; emysl Lubal ; Jakub Van&#x11b ; k ; Petr Hermann ; Isabel Santos
• 关键词：Cyclen derivative ; Methylphosphonic acid monoethylester arms ; Samarium and holmium stability constants ; Decomplexation kinetics ; Radiolanthanide complexes ; Biodistribution
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2008
• 期刊代码：53_01620134
• 类别：ch
• 出版时间：July 2008
• 卷：102
• 期：7
• 页码：1531-1540
• 文件大小：260 K

摘要

The novel methylphosphonic acid monoethylester (H₄dotp^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 H₄dota. The stability constants of the Ln(III)-H₄dotp^OEt complexes are surprisingly much lower that those of H₄dota (H₄dota = 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 H₄dota complexes, but still much more inert than complexes of open-chain ligands. Nevertheless, the synthesis of ¹⁵³Sm and ¹⁶⁶Ho 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 H₄dota complexes with the same metals.