Auger electron emitters are considered to be a promising strategy for targeted radionuclide therapy of metastatic diseases, given their high linear energy transfer (LET) and short range in tissue which could potentially limit normal tissue toxicity. Particularly Auger electron emitters that can be targeted into the DNA of tumor cells have been considered as an attractive cancer therapy in the past decade. In this study, the efficiency of the Auger electron emitter ¹²³I (half-life 13.2 h) to induce chromosomal damage was investigated by using the cytokinesis-block micronucleus assay. A stannylated deoxyuridine was synthesized and radiolabeled with ¹²³I, resulting in ¹²³IUdR that carried the Auger electron emitter across the nuclear membrane and allowed its incorporation into newly synthesized DNA. The DNA damage caused by the ¹²³I Auger cascade was estimated by evaluating the induced micronuclei frequencies in human peripheral blood lymphocytes obtained from three different donors. The isolated lymphocytes were stimulated with phytohemagglutinin (1 mg/ml) for 48 h before pulse labeling with ¹²³IUdR and the S-phase fraction was determined using flow cytometry. Geant4 Monte Carlo calculations were performed to determine the absorbed dose in cells by the Auger emitter. The relative biological effectiveness (RBE) was calculated by comparing the dose response curves for ¹²³IUdR with the reference dose response curves, obtained with ⁶⁰Co γ-ray irradiation in this study, for lymphocytes of the same donors. This resulted in a range of individual RBE values from 3 up to 10, depending on the donor and the radiation dose. In addition, dose limiting RBE values (RBE_Max) were calculated for each donor and ranged from 5 to 11, dependent on the inherent radiosensitivity of the donors. This study provides valuable information on the RBE of Auger electron emitter ¹²³I, which is identified as a promising theranostic radionuclide for future targeted radionuclide therapy.

俄歇电子发射器被认为是针对转移性疾病的放射性核素靶向治疗的有前途的策略，因为它们的线性能量转移（LET）高且组织范围短，可能会限制正常的组织毒性。在过去的十年中，特别是可以靶向肿瘤细胞DNA的俄歇电子发射器被认为是一种有吸引力的癌症治疗方法。在这项研究中，通过使用胞质阻滞微核试验研究了俄歇电子发射器¹²³ I（半衰期13.2小时）诱导染色体损伤的效率。合成了甲锡烷基化的脱氧尿苷，并用¹²³ I进行了放射性标记，结果得到¹²³IUdR携带俄歇电子发射器穿过核膜，并使其掺入新合成的DNA中。通过评估从三个不同供体获得的人外周血淋巴细胞中诱导的微核频率，估算了由¹²³ I Auger级联引起的DNA损伤。用植物血凝素（1 mg / ml）刺激分离的淋巴细胞48 h，然后用¹²³ IUdR进行脉冲标记，并使用流式细胞仪测定S期分数。进行Geant4蒙特卡洛计算以确定俄歇发射极在细胞中的吸收剂量。通过比较¹²³的剂量反应曲线来计算相对生物学有效性（RBE）对于相同供体的淋巴细胞，在本研究中使用⁶⁰ Coγ射线照射获得的具有参考剂量反应曲线的IUdR 。这导致单个RBE值的范围从3到10，具体取决于供体和辐射剂量。此外，根据每个供体的固有放射敏感性，计算了每个供体的剂量限制RBE值（RBE _Max），范围为5至11。这项研究提供了有关俄歇电子发射器¹²³ I的RBE的有价值的信息，该电子被认为是有希望的治疗性放射性核素，可用于未来的靶向放射性核素治疗。