Population pharmacokinetic modeling in radiopharmaceutical therapy: a review

Population pharmacokinetic (PopPK) has emerged as a robust framework for characterizing inter-individual 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.