Bioanalytic Hybrid System Merging 3-Dimensional Cell Culture and Chromatographic Precision for Unprecedented Preclinical Insights in Molecular Imaging

We introduce a unique bioanalytic hybrid system for the preclinical assessment of radiotracer candidates, combining a 3-dimensional cell culture on an artificial extracellular matrix functioning as a stationary phase and a chromatographiclike system array. Methods: Silk fibroin sponges were applied to simulate an extracellular matrix and to function as a stationary phase. Different cell lines were grown on the silk scaffold and used to investigate radiopharmaceuticals in a small-animal PET/CT system. Results: Our system integrates with the strength of chromatographic systems, allowing high throughput, full automation, and online processing with the complexity of an advanced 3-dimensional cell culture for in vitro modeling of real tissuelike geometry, morphology, and dynamics. Conclusion: This system holds great potential to study newly developed radiotracers for applications in binding studies and assessment of unspecific binding. It might help to decrease the translational gap from in vitro cell cultures to in vivo studies while it aligns with the 3R principle (reduce, replace, refine) of animal testing.