Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose–response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125. We compared the energy deposition and single strand break (SSB) yield at each base pair location in a short B-form DNA (B-DNA) geometry with existing simulation and experimental data, considering both physical direct and chemical indirect hits. Additionally, we evaluated dosimetric differences between our high-resolution B-DNA target and a previously published simple B-DNA geometry. Overall, our benchmarking results for SSB yield from I-125 decay exhibited good agreement with both simulation and experimental data. Using this simulation, we then evaluated the SSB and double strand break (DSB) yields caused by a theranostic Br-77-labeled poly ADP ribose polymerase (PARP) inhibitor radiopharmaceutical. The results indicated a predominant contribution of chemical indirect hits over physical direct hits in generating SSB and DSB. This study lays the foundation for future investigations into the nano-dosimetric properties of RPT.
放射性药物疗法（RPT）正逐渐发展为一种有前景的癌症治疗策略。随着人们对俄歇电子等短程粒子的兴趣日益增长，理解其在脱氧核糖核酸（DNA）层面的剂量-响应关系变得至关重要。本研究利用Geant4-DNA工具包评估了由发射俄歇电子的同位素碘-125引起的DNA损伤。我们通过考虑物理直接作用和化学间接作用，将短B型DNA（B-DNA）结构中每个碱基对位置的能量沉积和单链断裂（SSB）产率与现有模拟及实验数据进行了比较。此外，我们还评估了高分辨率B-DNA靶标与先前发表的简化B-DNA几何结构之间的剂量学差异。总体而言，我们对碘-125衰变引起的SSB产率的基准测试结果与模拟和实验数据均表现出良好的一致性。基于此模拟，我们进一步评估了由治疗诊断性溴-77标记的聚ADP核糖聚合酶（PARP）抑制剂放射性药物引起的SSB和双链断裂（DSB）产率。结果表明，在产生SSB和DSB过程中，化学间接作用的贡献显著高于物理直接作用。本研究为未来探索RPT的纳米剂量学特性奠定了基础。
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