Radiobiological Aspects of PRRT

This webinar will examine the fundamental differences between targeted radionuclide therapy (TRT) and conventional external beam radiotherapy (EBRT), integrating physical, dosimetric, and radiobiological perspectives relevant to clinical practice. Drawing on the EANM–ESTRO joint session, the first part will outline how TRT’s systemic administration, patient-specific pharmacokinetics, protracted low dose-rate delivery, and highly heterogeneous intratumoral distribution distinguish it from the controlled, high dose-rate, fractionated paradigm of EBRT. Emphasis will be placed on implications for treatment planning, activity prescription, imaging-based dosimetry, and the limitations of directly translating EBRT concepts such as uniform dose coverage and standard fractionation models to TRT.

The second part will focus on how absorbed dose, dose rate, and spatial heterogeneity influence biological effectiveness and clinical outcomes in TRT. Key topics include sublethal damage repair during continuous irradiation, challenges in applying conventional radiobiological models, the impact of microscopic dose non-uniformity (especially for β- versus α-emitting therapies), and the relationship between local tumor control and systemic effects, including immune modulation. The session aims to equip nuclear medicine physicians and medical physicists with a conceptual framework to interpret dosimetry results, personalize treatments, and critically evaluate emerging combination strategies as TRT evolves toward a quantitatively driven radiotherapy modality.

• Differentiate the fundamental physical and clinical characteristics of TRT versus EBRT, including source geometry, temporal delivery, dose-rate profiles, and implications for treatment planning and prescription.
• Explain how pharmacokinetics and biodistribution govern absorbed dose in TRT, and why activity administration alone is an insufficient surrogate for delivered dose and therapeutic effect.
• Assess the impact of dose rate and protracted irradiation on radiobiological response, including sublethal damage repair, limitations of conventional linear-quadratic modeling, and consequences for tumor control and normal tissue toxicity.
• Recognize the clinical significance of spatial dose heterogeneity at organ, tumor, and cellular scales, particularly differences between β-emitting and α-emitting radiopharmaceutical therapies.
• Interpret the relationship between dosimetry metrics and clinical outcomes, including local control, toxicity, and potential systemic (immune-mediated) effects.
• Apply these concepts to support patient-specific dosimetry, treatment personalization, and multidisciplinary decision-making in modern targeted radionuclide therapy practice.

• This webinar is intended for nuclear medicine physicians and medical physicists involved in targeted radionuclide therapy, including early-career professionals and practitioners seeking to deepen their understanding of the physical and radiobiological principles underpinning modern TRT practice.