Rey A.M.,Catedra de Radioquimica
Current Medicinal Chemistry | Year: 2010
Radiometals have become increasingly important because of their use both for diagnostic molecular imaging and therapy in Nuclear Medicine. The focus is on the study of biochemical processes at cellular and sub-cellular level in order to detect metabolic abnormalities associated with various diseases. For that purpose, molecules that selectively accumulate in the organ or tissue of interest by a specific mechanism such as receptor binding or interaction with biomolecules are labeled with 99mTc, 68Ga, 153Sm, 186/188Re, 177Lu, among others and used as radiopharmaceuticals. However, considerable effort is necessary to combine these radionuclides with biomolecules relevant to different pathological conditions. Intensive research on the coordination chemistry of these metals has led to novel labeling methods that yield stable compounds which retained the original biological activity of the ligand. Chemical aspects and clinical applications will be reviewed in this paper. © 2010 Bentham Science Publishers Ltd.
Giglio J.,Catedra de Radioquimica |
Fernandez S.,Catedra de Radioquimica |
Pietzsch H.-J.,Helmholtz Center Dresden |
Dematteis S.,Catedra de Inmunologia |
And 3 more authors.
Nuclear Medicine and Biology | Year: 2012
The evaluation of oxygenation status of solid tumors is an important field of radiopharmaceutical research. With the aim to develop new potential 99mTc-radiopharmaceuticals for imaging hypoxia, we have synthesized two novel isocyanide derivatives of metronidazole, which has demonstrated high affinity for hypoxic tumors in vitro and in vivo. Methods: Metronidazole derivatives 4-isocyano-N-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]butanamide (M1) and 1-(4-isocyanobutanoyl)-4-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]piperazine (M2) were synthesized, and labeling was performed through preparation of their corresponding 99mTc-(4+1) complexes, 99mTc-NS3M1 and 99mTc-NS3M2. The structure of the technetium complexes was corroborated by preparation and characterization of the corresponding rhenium complexes. We have studied the main physicochemical properties (stability, lipophilicity and plasma protein binding). Biological behavior in HCT-15 cells both in oxia and in hypoxia was assessed. Biodistribution in normal mice and in animals bearing induced 3LL Lewis murine lung carcinoma was also studied. Results: Metronidazole derivatives were successfully synthesized. Labeling with high radiochemical purity was achieved for both ligands. 99mTc complexes were stable in labeling milieu and human plasma. However, presence of the piperazine linker in M2 resulted in higher lipophilicity and protein binding. Although cell uptake in hypoxic conditions was observed for both radiotracers, 99mTc-NS3M2 biodistribution was considered unsuitable for a potential radiopharmaceutical due to high liver uptake and poor blood clearance. However, 99mTc-NS3M1 demonstrated a very favorable in vivo profile both in normal mice and in mice bearing induced tumors. Conclusion: Selective uptake and retention in tumor together with favorable tumor/muscle ratio make 99mTc-NS3M1 a promising candidate for further evaluation as potential hypoxia imaging agent in tumors. © 2012 Elsevier Inc..