Bioorganic & Medicinal Chemistry Letters 2011-01-01

Synthesis and biological characterisation of novel dithiocarbamate containing 5-nitroimidazole (99m)Tc-complexes as potential agents for targeting hypoxia.

Javier Giglio, Soledad Fernández, Ana Rey, Hugo Cerecetto

Index: Bioorg. Med. Chem. Lett. 21(1) , 394-7, (2011)

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Abstract

With the aim to develop new potential (99m)Tc-radiopharmaceuticals for imaging hypoxia based on the formation of Tc-nitrido complexes, two novel dithiocarbamate containing metronidazole derivatives (L1 and L2) have been prepared and characterised. The synthesis of L1 and L2 was achieved in excellent yield and high purity. Labelling with (99m)Tc was successfully performed using a low ligand concentration (approximately 2-3mg) and the desired products were obtained with high radiochemical purity (>90%). Lipophilicity, plasma protein binding, and biodistribution in normal- and tumour-bearing-CD1 mice studies were performed to asses the potentiality for nuclear medicine oncology. According to the physicochemical and biological behaviour both in healthy animals and in animals bearing solid tumours complex dtcTc1 could be considered as a starting point for the development of new radiopharmaceuticals for imaging hypoxia.Copyright © 2010 Elsevier Ltd. All rights reserved.