Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue

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Título

Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue

Tema

TECNECIO-COMPLEJOS
TEJIDO HIPOXICO
BIBLIOGRAFIA NACIONAL QUIMICA
2012

Abstract

An important issue in the development of metal-based radiopharmaceuticals is the selection of the labelling strategy in order to couple the metal to the pharmacophore without losing the biological activity. With the aim to evaluate the correlation between ligand denticity and biological behaviour of the corresponding 99mTc complexes, we designed a tridentate and a bidentate 5-nitroimidazole derivatives suitable for 99mTc(I) tricarbonyl complexation and with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis. Ligands were synthesized using metronidazol, a pharmaceutical containing the bioreductive pharmacophore as starting material. The chelating units were connected to the pharmacophore using the click reaction of Huisgen. Both 99mTc complexes were obtained in high yield and were hydrophilic and stable in labelling milieu. The complex obtained from the tridentate ligand exhibited high stability in human plasma, low protein binding and a favourable biodistribution characterized by low blood and liver uptake, fast elimination and negligible uptake in other organs or tissues. Selective uptake and retention in tumour together with favourable tumour/muscle ratio makes this 99mTc-complex a promising candidate for further evaluation as potential hypoxia imaging agent in tumours. The bidentate ligand, on the other hand, yielded a less stable 99mTc-complex that experimented hydrolysis in vitro and decomposition in human plasma and showed high protein binding, high blood and liver uptake and moderate excretion. Although selective uptake and retention in tumour was also observed physicochemical and biological behaviour are inadequate for in vivo use, demonstrating that denticity of the ligand is particularly important and that tridentate ligands are preferable in order to prepare 99mTc-tricarbonyl complexes for Nuclear Medicine imaging

Autor

Fernández, Soledad
Cerecetto, Hugo

Fuente

Bioorganic and Medicinal Chemistry v. 20, 2012. -- p. 4040-48

Editor

Elsevier

Fecha

2012

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Artículo

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http://dx.doi.org/10.1016/j.bmc.2012.05.010

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Original Format

PDF
Fecha de agregación
August 10, 2012
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
Etiquetas
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Citación
Fernández, Soledad, “Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed September 15, 2019, http://riquim.fq.edu.uy/items/show/58.
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