Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins : Toward Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies - 19/11/25

Doi : 10.1016/j.cpet.2025.08.004

Nouran R.R. Zaid, PhD ^a,^⁎ , Deni Hardiansyah, Dr.sc.hum ^b, Tahir Yusufaly, PhD ^a, Arman Rahmim, PhD, DABSNM ^c,^d
^a Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA
^b Medical Physics and Biophysics Research Group, Department of Physics, Faculty of Mathematics and Natural Sciences (FMIPA), Universitas Indonesia, Indonesia
^c Department of Radiology, Physics and Biomedical Engineering, University of British Columbia, Vancouver, Canada
^d Integrative Oncology, BC Cancer Research Institute, Vancouver, Canada

^∗Corresponding author. Department of Radiology and Radiological Science, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21287.Department of Radiology and Radiological ScienceJohns Hopkins University1550 Orleans StreetBaltimoreMD21287

Résumé

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.

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Keywords : Radiopharmaceutical therapy, Theranostics, PBPK models, Digital twins, Verification, Validation, Uncertainty quantification, Personalized dosimetry

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Key points

Introduction

Physiologically based pharmacokinetic modeling in radiopharmaceutical therapies

Framework and Parameterization of Physiologically Based Pharmacokinetic Models

Approaches to Building Physiologically Based Pharmacokinetic Models

Verification, validation, and uncertainty quantification for physiologically based pharmacokinetic models in radiopharmaceutical therapies

Uncertainty Quantification

Extending PBPK modeling to dynamic theranostic digital twins: emerging verification, validation, and uncertainty quantification challenges

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Vol 21 - N° 1

P. 101-115 - janvier 2026 Retour au numéro

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An Overview of Physiologically Based Pharmacokinetic (PBPK) and Population Pharmacokinetic (PopPK) Models : Applications to Radiopharmaceutical Therapies for Analysis and Personalization
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Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins : Toward Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies - 19/11/25

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