Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Int J Mol Sci. 2024 Sep 29;25(19):10490. doi: 10.3390/ijms251910490.
This study conducts a comparative analysis of cystamine (RSSR), a disulfide, and cysteamine (RSH), its thiol monomer, to evaluate their efficacy as radioprotectors and antioxidants under high linear energy transfer (LET) and high-dose-rate irradiation conditions. It examines their interactions with reactive primary species produced during the radiolysis of the aqueous ferrous sulfate (Fricke) dosimeter, offering insights into the mechanisms of radioprotection and highlighting their potential to enhance the therapeutic index of radiation therapy, particularly in advanced techniques like FLASH radiotherapy. Using Monte Carlo multi-track chemical modeling to simulate the radiolytic oxidation of ferrous to ferric ions in Fricke-cystamine and Fricke-cysteamine solutions, this study assesses the radioprotective and antioxidant properties of these compounds across a variety of irradiation conditions. Concentrations were varied in both aerated (oxygen-rich) and deaerated (hypoxic) environments, simulating conditions akin to healthy tissue and tumors. Both cystamine and cysteamine demonstrate radioprotective and strong antioxidant properties. However, their effectiveness varies significantly depending on the concentration employed, the conditions of irradiation, and whether or not environmental oxygen is present. Specifically, excluding potential in vivo toxicity, cysteamine substantially reduces the adverse effects of ionizing radiation under aerated, low-LET conditions at concentrations above ~1 mM. However, its efficacy is minimal in hypoxic environments, irrespective of the concentration used. Conversely, cystamine consistently offers robust protective effects in both oxygen-rich and oxygen-poor conditions. The distinct protective capacities of cysteamine and cystamine underscore cysteamine's enhanced potential in radiotherapeutic settings aimed at safeguarding healthy tissues from radiation-induced damage while effectively targeting tumor tissues. This differential effectiveness emphasizes the need for personalized radioprotective strategies, tailored to the specific environmental conditions of the tissue involved. Implementing such approaches is crucial for optimizing therapeutic outcomes and minimizing collateral damage in cancer treatment.
本研究对二硫代胱氨酸（RSSR）和半胱胺（RSH）这两种巯基单体进行了对比分析，以评估它们在高传能线密度（LET）和高剂量率照射条件下作为辐射防护剂和抗氧化剂的功效。研究考察了它们与辐解产生的活性初始物质的相互作用，这些初始物质存在于硫酸亚铁（Fricke）水基剂量计中，为辐射防护机制提供了深入了解，并强调了它们提高放射治疗治疗指数的潜力，特别是在 FLASH 放射治疗等先进技术中。本研究采用蒙特卡罗多轨迹化学建模，模拟 Fricke-半胱胺和 Fricke-半胱氨酸溶液中二价铁离子的辐解氧化，评估了这些化合物在各种辐照条件下的辐射防护和抗氧化特性。在有氧（富含氧气）和乏氧（缺氧）环境中改变浓度，模拟类似于健康组织和肿瘤的条件。半胱胺和胱胺均表现出辐射防护和强大的抗氧化特性。然而，它们的有效性在很大程度上取决于所使用的浓度、辐照条件以及环境中是否存在氧气。具体来说，在有氧、低 LET 条件下，排除潜在的体内毒性，半胱胺在浓度高于约 1mM 时可显著降低电离辐射的不良影响。然而，在缺氧环境下，其效果微不足道，无论使用何种浓度。相反，胱胺在富氧和贫氧条件下均能提供稳定的保护作用。半胱胺和胱胺的保护能力存在差异，突显了半胱胺在旨在保护健康组织免受辐射损伤的放射治疗环境中具有增强的潜力，同时有效靶向肿瘤组织。这种差异的有效性强调了需要根据组织的特定环境条件制定个性化的辐射防护策略。实施这些方法对于优化治疗结果和最大限度地减少癌症治疗中的附带损伤至关重要。
