PRECLINICAL EVALUATION OF METALLODRUGS FOR ANTICANCER THERAPY
In collaboration with national and international research groups, we have investigated complexes with a variety of d-transition metals (Ru, V, Ag, Cu, Ga, In) as prospective metallodrugs for anticancer therapy, with a focus on the study of cell uptake and death mechanisms. Taking advantage of the unique expertise of the radiopharmaceutical sciences group, some of these studies included the evaluation of radioactive counterparts (e.g 67Ga and 111In) for a more straightforward quantification of cellular uptake and in vivo assessment of the biodistribution and stability of the compounds. Profiting from the availability of the nuclear microscopy facility at the CTN/IST, the uptake of a copper complex by PC3 cells was also ascertained by simultaneous application of PIXE (Particle Induced X-ray Emission), RBS (Rutherford Backscattering Spectroscopy) and STIM (Scanning Transmission Ion Microscopy). These techniques, seldom used to evaluate the cellular uptake of anticancer metallodrugs, showed a preferential localization of Cu in the nuclear and perinuclear regions thus giving a clue for possible cellular targets.