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

Source: [Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins: Towards Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies](<https://www.sota2.com/research/paper/68fa4bf61e209131ce949a3a>)

Collection index: [llms.txt](<https://www.sota2.com/research/llms.txt>)

Data updated: 2025-10-30T05:01:12.438Z

Authors: Nouran R. R. Zaid, Deni Hardiansyah, Tahir Yusufaly, Arman Rahmim (3,4,5) \_\_INSTITUTION\_4\_\_ Department of Radiology, Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA, (2) Medical Physics, Biophysics, Physics Department, Faculty of Mathematics, Natural Sciences, Universitas Indonesia, Depok, Indonesia, (3) Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada. (4) Departments of Radiology, Physics, University of British Columbia, Vancouver, BC, Canada, (5) School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada)

Published: 2025-09-25T23:48:22.000Z

## Abstract

Physiologically based pharmacokinetic (PBPK) models provide a mechanistic framework for simulating radiopharmaceutical kinetics and estimating patient-specific absorbed doses (ADs). PBPK models incorporate prior knowledge of patient physiology and drug-specific properties, which can enhance the models predictive performance. PBPK models can ultimately be used to predict treatment response and thereby enable theranostic digital twins (TDTs) for personalized treatment planning in radiopharmaceutical therapies (RPTs). To achieve this potential of precision RPT, however, the reliability of the underlying modeling, including the PBPK-based dosimetry, 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. Key methodologies for PBPK model VVUQ are discussed, including goodness-of-fit (GOF) assessment, prediction evaluation, and uncertainty propagation.

## Recorded benchmark results

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## Original sources and implementation

[Original paper](<https://arxiv.org/abs/2509.21697>)

[PDF](<https://arxiv.org/pdf/2509.21697.pdf>)