A novel application of advanced elemental imaging offers cutting edge in vitro assays with more predictive power on the efficacy of anticancer drugs in preclinical development compared to two dimensional cell culture models. We propose LA-ICP-MS analysis of multicellular spheroids, which are increasingly being used as three dimensional (3D) models of
tumors, for improving the in vitro evaluation of anticancer metallodrugs. The presented strategy is very well suited for screening drug-
tumor penetration, a key issue for drug efficacy. A major advantage of
tumor spheroid models is that they enable us to create a tissue-like structure and function. With respect to 2D culture on the one hand and in vivo models on the other, multicellular spheroids thus show intermediate complexity, still allowing high repeatability and adequate through-put for drug research. This strongly argues for the use of spheroids as bridging models in preclinical anticancer drug development. Probing the lateral
platinum distribution within these
tumor models allows visualizing the penetration depth and targeting of
platinum-based complexes. In the present study, we show for the first time that spatially-resolved
metal accumulation in
tumor spheroids upon treatment with
platinum compounds can be appropriately assessed. The optimized LA-ICP-MS setup allowed discerning the
platinum localization in different regions of the
tumor spheroids upon compound treatment at biologically relevant (low micromolar) concentrations. Predominant
platinum accumulation was observed at the periphery as well as in the center of the spheroids. This corresponds to the proliferating outermost layers of cells and the necrotic core, respectively, indicating enhanced
platinum sequestration in these regions.