Radiopharmaceutical Dosimetry Requires Harmonized Standards to Bridge Physics, Biology, and AI for Personalized Therapy
Background
The field of nuclear medicine is rapidly advancing with targeted radionuclide therapies, yet a critical gap exists in personalizing dose estimation. Current dosimetry methods often fall short in accurately predicting therapeutic efficacy and mitigating organ toxicity for individual patients. This limitation hinders the full potential of precision medicine in radiopharmaceutical therapy (RPT), where optimal dosing is crucial for maximizing tumor kill while minimizing damage to healthy tissues, particularly in peptide receptor radionuclide therapy (PRRT) settings.
Study Design
This review critically examined the current landscape of dosimetry methods by conducting a comprehensive literature search of 177Lu peptide receptor radionuclide therapy (PRRT) studies published between 2020 and 2025. The authors evaluated methodological heterogeneity across studies, focusing on established techniques like Medical Internal Radiation Dose (MIRD) schema, voxel-based S-values, and Monte Carlo (MC) simulations, alongside emerging artificial intelligence (AI)-assisted segmentation tools. The primary goal was to quantify and analyze dose variations across organs and identify contributing factors.
Results
Findings from the extensive literature review revealed persistent and significant inconsistencies in absorbed dose estimates across 177Lu PRRT studies. Reported kidney doses varied widely, ranging from 0.3-0.9 Gy/GBq, while tumor doses showed even greater variability, from 1-10 Gy/GBq. These substantial differences were largely attributed to methodological discrepancies in imaging protocol timing, segmentation strategies, and time-point sampling across the reviewed studies. The review also highlighted the translational relevance of incorporating biologically informed dosimetry models, such as those considering relative biological effectiveness (RBE), and the future integration with dose-point kernel (DPK) and dose-volume histogram (DVH) computational frameworks. > The observed 3-fold variation in kidney doses and 10-fold variation in tumor doses underscore the urgent need for standardized dosimetry practices to enable truly personalized and effective radiopharmaceutical therapy.
Key Findings
- Kidney absorbed doses in
177Lu PRRTstudies vary significantly, from 0.3-0.9 Gy/GBq. - Tumor absorbed doses in
177Lu PRRTstudies show wide variability, ranging 1-10 Gy/GBq. - Methodological differences in imaging timing, segmentation, and time-point sampling drive dose estimate inconsistencies.
- Current dosimetry methods require integration of physics, biology (e.g.,
RBE), andAIfor personalization. - Harmonized, reproducible standards are essential to transform dosimetry into a predictive tool for individualized therapy.
Why It Matters
The current lack of harmonized standards in radiopharmaceutical dosimetry directly impacts the clinical translation and efficacy of targeted radionuclide therapies. For clinicians and researchers, this means that dose estimates for 177Lu PRRT are not reliably comparable across institutions or studies, hindering the development of optimized treatment protocols. Establishing reproducible, harmonized dosimetry standards is critical to move beyond empirical dosing towards truly predictive and individualized patient management. This shift would enable more precise dose prescription, better prediction of therapeutic response, and proactive mitigation of organ toxicity, ultimately improving patient outcomes and accelerating the development of next-generation radiopharmaceuticals.
radiopharmaceutical-therapy
dosimetry
nuclear-medicine
177lu
prrt
ai