De Sio Chiara, Ballisat Laura, Beck Lana, Guatelli Susanna, Sakata Dousatsu, Shi Yuyao, Duan Jinyan, Sabah Lujin Abu, Velthuis Jaap, Rosenfeld Anatoly
School of Physics, University of Bristol, Bristol, UK.
School of Physics, University of Bristol, Bristol, UK.
Phys Med. 2025 Jan;129:104860. doi: 10.1016/j.ejmp.2024.104860. Epub 2024 Dec 6.
Targeted alpha therapies show great potential for cancer treatment due to their high linear energy transfer (LET) and low range. At is currently employed in clinical trials. Targeted alpha therapies (TAT) are effective as an adjuvant treatment for cancer or to treat micrometastases and diffuse cancers. A deeper understanding of the induced initial damage is crucial to enhance treatment planning.
This study shows Geant4(-DNA)-based simulations to calculate absorbed dose profiles and DNA damaging potential in intravenously administered TAT with At. It assumes radionuclide decay on the blood vessel wall, and calculates the DNA damage in the surrounding tissue.
The calculated dosimetric quantities show that the effect of such treatment is mainly due to the emitted alpha particles, and is localised in a region of up to 80μm from the blood vessel. The RBE of the treatment is in the range 2.5-4, and is calculated as a function of the number of double-strand breaks.
Targeted therapies with At are effective within the range of the emitted alpha particles. With its capacity to induce complex DNA damage in such a short range, it is very promising for localised treatment of small tumour cells or micrometastases.
靶向α疗法因其高线性能量传递（LET）和低射程而在癌症治疗中显示出巨大潜力。目前已应用于临床试验。靶向α疗法（TAT）作为癌症的辅助治疗或治疗微转移和弥漫性癌症是有效的。深入了解诱导的初始损伤对于改进治疗方案至关重要。
本研究展示了基于Geant4（-DNA）的模拟，以计算静脉注射含砹的TAT时的吸收剂量分布和DNA损伤潜力。假设放射性核素在血管壁上衰变，并计算周围组织中的DNA损伤。
计算得到的剂量学量表明，这种治疗的效果主要归因于发射的α粒子，且局限于距血管80μm以内的区域。该治疗的相对生物效应（RBE）在2.5 - 4范围内，并作为双链断裂数的函数进行计算。
含砹的靶向疗法在发射的α粒子射程范围内是有效的。由于其能够在如此短的射程内诱导复杂的DNA损伤，对于局部治疗小肿瘤细胞或微转移具有很大的前景。
