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MINI REVIEW article

Front. Nucl. Med.

Sec. Dosimetry and Radiation Safety

Volume 5 - 2025 | doi: 10.3389/fnume.2025.1695332

This article is part of the Research TopicInsights into Dosimetry and Investigation of Dose Effects in Molecular Radiotherapy (MRT)View all articles

Population Pharmacokinetic Modeling in Radiopharmaceutical Therapy: A Review

Provisionally accepted
  • 1Universitas Indonesia, Depok, Indonesia
  • 2Badan Riset dan Inovasi Nasional Republik Indonesia, Central Jakarta, Indonesia
  • 3Universitat Ulm, Ulm, Germany

The final, formatted version of the article will be published soon.

Population pharmacokinetic (PopPK) has emerged as a robust framework for characterizing interindividual variability in the absorbed dose estimates in radiopharmaceutical therapy (RPT). By enabling the analysis of biokinetic data from heterogeneous patient populations, PopPK allows individualized absorbed dose estimates while simultaneously leveraging population-level information. This review presents and evaluates the current applications of PopPK, such as nonlinear mixed-effects modeling (NLMEM) and Bayesian fitting methods in RPT, emphasizing its advantages over traditional individual-based modeling approaches. We summarize key studies that have implemented PopPK for modeling radiopharmaceutical biokinetics, with a focus on time-integrated activity (TIA) estimation, including single-time-point (STP) dosimetry, uncertainty analysis, as well as pharmacodynamic (PD) analysis. The flexibility of PopPK in handling sparse and irregularly sampled data makes it particularly relevant for clinical scenarios where comprehensive imaging schedules are impractical. However, despite its potential, the widespread adoption of PopPK in RPT remains limited due to challenges such as computational complexity and the need for specialized expertise. This review discusses critical aspects of PopPK implementation while emphasizing the importance of interdisciplinary collaboration in translating PopPK methodologies into clinical practice. Future directions include integrating PopPK into adaptive dosimetry frameworks and applying it in STP dosimetry and PD modeling to optimize treatment personalization. By providing a comprehensive overview of PopPK applications in RPT, this review aims to facilitate the integration of advanced modeling techniques into routine clinical workflows, ultimately supporting the development of accurate and precise RPTs.

Keywords: POPPK, RPT, NLMEM, STP, PKPD

Received: 29 Aug 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Hardiansyah, Patrianesha and Glatting. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Deni Hardiansyah, denihardiansyah@ui.ac.id

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