Multidimensional in silico evaluation of fluorine-18 radiopharmaceuticals: integrating pharmacokinetics, ADMET, and clustering for diagnostic stratification.

Fluorine-18-labeled radiopharmaceuticals are central to PET-based oncology imaging, yet comparative evaluations of their mechanistic behavior and diagnostic potential remain fragmented. In this study, we present a multidimensional in silico framework integrating pharmacokinetic modeling, structural ADMET prediction, and unsupervised clustering to systematically evaluate five widely used F-labeled PET radiopharmaceuticals: [F]FDG, [F]FET, [F]DOPA, [F]FMISO, and [F]FLT. Each radiopharmaceutical was simulated using a harmonized three-compartment model in COPASI to capture uptake dynamics under both normal and pathological conditions.