Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins: Towards Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies
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arXiv
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| Autores principales: | , , , |
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| Formato: | Preprint |
| Publicado: |
2025
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| _version_ | 1866908616580136960 |
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| author | Zaid, Nouran R. R. Hardiansyah, Deni Yusufaly, Tahir Rahmim, Arman |
| author_facet | Zaid, Nouran R. R. Hardiansyah, Deni Yusufaly, Tahir Rahmim, Arman |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2509_21697 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins: Towards Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies Zaid, Nouran R. R. Hardiansyah, Deni Yusufaly, Tahir Rahmim, Arman Medical Physics 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. |
| title | Verification, Validation, and Uncertainty Quantification (VVUQ) of Physiologically Based Pharmacokinetic Models for Theranostic Digital Twins: Towards Reliable Model-Informed Treatment Planning for Radiopharmaceutical Therapies |
| topic | Medical Physics |
| url | https://arxiv.org/abs/2509.21697 |