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• W2034978826 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." @default.
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• W2034978826 date "2012-07-01" @default.
• W2034978826 modified "2023-09-23" @default.
• W2034978826 title "Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue" @default.
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• W2034978826 doi "https://doi.org/10.1016/j.bmc.2012.05.010" @default.
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