Department of Experimental Physics, Institute of Physics and Technology, Ural Federal University, Yekaterinburg, Russia.
Physics Department, Faculty of Science, Al-Azhar University, Assuit, Egypt.
Int J Radiat Biol. 2020 Jun;96(6):779-789. doi: 10.1080/09553002.2020.1729441. Epub 2020 Mar 3.
In recent years, radionuclides like Lu have been considered promising material for the creation of therapeutic radiopharmaceuticals. With the therapeutic use of radiopharmaceuticals, the absorbed doses per tumor may exceed 10 Gy. It is extremely important that doses absorbed by healthy organs and tissues do not exceed the threshold for the incidence of deterministic effects. The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide Lu is a beta-emitting nuclide with a maximal energy of 0.49 MeV and a half-life of 6.6 days (161 h). Two therapeutic agents were considered: methylene diphosphonate (MDP) and ethylenediamine tetramethylene phosphonic acid (EDTMP). Both drugs contain phosphorus compounds in their composition, which ensures high tropism in bone tissue. For both drugs, biokinetic models of Lu's behavior in the human body are created. A number of studies have shown that the radiochemical stability of these drugs is about 99%: these calculations took into account the presence of a free Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals Lu-MDP and Lu-EDTMP, as well as the currently used drugs Sm-EDTMP and SrCl, are compared. In order to assess the risk of the patient's exposure to a radiopharmaceutical, the absorbed doses are calculated for each organ where the radioactive label is mainly deposited: the kidneys, red bone marrow, liver and bone surface. The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug Lu-MDP is faster than other drugs when it comes to the full realization of the expected dose; therefore, a therapeutic effect is achieved faster when it is used. The slowest absorbed dose accumulates when strontium chloride is used. To compare the effectiveness of preparations based on the Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (SrCl and Sm-EDTMP) was performed. For Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the Lu-MDP and Lu-EDTMP radiopharmaceuticals. According to the results of the calculations, Lu-EDTMP and Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.
近年来，镥等放射性核素已被认为是治疗性放射性药物研发的有前途的材料。放射性药物治疗中，肿瘤吸收的剂量可能超过 10Gy。至关重要的是，健康器官和组织吸收的剂量不能超过确定性效应发生的阈值。本文分析了放射性核素 177 镥在缓解骨转移疼痛方面的潜在应用。放射性核素 Lu 是一种β发射核素，最大能量为 0.49MeV，半衰期为 6.6 天（161 小时）。考虑了两种治疗剂：亚甲基二膦酸盐（MDP）和乙二胺四亚甲基膦酸（EDTMP）。这两种药物的成分中都含有磷化合物，这确保了它们在骨组织中的高靶向性。为这两种药物创建了 Lu 在人体内行为的生物动力学模型。多项研究表明，这些药物的放射化学稳定性约为 99%：这些计算考虑了每种溶液中游离 Lu 放射性核素的存在。比较了使用放射性药物 Lu-MDP 和 Lu-EDTMP 以及目前使用的 Sm-EDTMP 和 SrCl 时器官和组织中的吸收剂量。为了评估患者接触放射性药物的风险，计算了放射性标记主要沉积的每个器官的吸收剂量：肾脏、红骨髓、肝脏和骨表面。使用不同药物在病变部位时，剂量积累的强度不同。与其他药物相比，Lu-MDP 药物更快地实现了预期剂量的完全实现；因此，当使用时，更快地达到治疗效果。当使用氯化锶时，吸收剂量的积累最慢。为了比较基于 Lu 放射性核素的制剂的有效性，对目前用于缓解骨转移的放射性药物（SrCl 和 Sm-EDTMP）进行了分析。对于 Sr，最脆弱的器官是肾脏、红骨髓和肝脏，而对于 Sm-EDTMP，最脆弱的是红骨髓骨。对于基于 Lu 放射性核素的放射性药物，最脆弱的器官是肾脏、肝脏和红骨髓。这证明了 Lu-MDP 和 Lu-EDTMP 放射性药物的有效性。根据计算结果，Lu-EDTMP 和 Lu-MDP 在缓解骨转移方面表现出最佳的治疗效果。
