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.

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential ^99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [¹⁸F]Fluoromisonidazole (FMISO) is also presented.