Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins: Toward Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies.

Physiologically based pharmacokinetic (PBPK) models provide a mechanistic framework for simulating radiopharmaceutical kinetics and estimating patient-specific absorbed doses. PBPK models incorporate prior knowledge of patient physiology and drug-specific properties. PBPK models can ultimately be used to predict treatment response and thereby enable theranostic digital twins for personalized treatment planning in radiopharmaceutical therapies (RPTs). To achieve this potential of precision RPTs, however, the reliability of the underlying modeling must be established through rigorous verification, validation, and uncertainty quantification (VVUQ). This review outlines the role of VVUQ in ensuring the credibility and clinical applicability of PBPK models in radiotheranostics.