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皮肤黑色素瘤小鼠模型中锂的生物分布和肾毒性研究:迈向实施锂中子俘获疗法的第一步。

Study of Lithium Biodistribution and Nephrotoxicity in Skin Melanoma Mice Model: The First Step towards Implementing Lithium Neutron Capture Therapy.

作者信息

Taskaeva Iuliia, Kasatova Anna, Surodin Dmitry, Bgatova Nataliya, Taskaev Sergey

机构信息

Laboratory of Ultrastructural Research, Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630060 Novosibirsk, Russia.

Budker Institute of Nuclear Physics, 630090 Novosibirsk, Russia.

出版信息

Life (Basel). 2023 Feb 14;13(2):518. doi: 10.3390/life13020518.

Abstract

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for malignant melanoma. The main issue of this technology is the insufficient selectivity of B accumulation in tumor cells. As a result of the neutron absorption by boron, an 84% energy release occurred within the cell by the nuclear reaction B (n, α)Li, which lead to tumor cell death. The use of lithium instead of boron brings a new unique opportunity-local 100% energy release-since all products of the Li (n, α)H reaction have high linear energy transfer characteristics. The aim of this study was to determine the concentrations of Li in the tumor, skin, blood, brain and kidney in experimental animals with B16 melanoma and to analyze the potential Li toxicity after lithium carbonate administration at single doses of 300 and 400 mg/kg. Lithium carbonate was chosen since there is a long-term experience of its use in clinical practice for the treatment of psychiatric disorders. The inductively coupled plasma atomic emission spectrometry was used to evaluate Li concentrations in tissue samples. The accumulation efficiency of Li in the tumor was the highest at a time point of 30 min (22.4 µg/g; at a dose of 400 mg/kg). Despite the high lithium accumulation in the kidneys, the pathological changes in kidney tissues were not found. Thus, lithium may actually be used for the Li-NCT development and future studies can be conducted using Li and following irradiation of tumor cells using the schemes of lithium administration tested in this work.

摘要

硼中子俘获疗法(BNCT)是恶性黑色素瘤颇具前景的治疗方法之一。该技术的主要问题在于硼在肿瘤细胞中的蓄积选择性不足。硼吸收中子后,核反应B(n,α)Li在细胞内释放了84%的能量,导致肿瘤细胞死亡。使用锂替代硼带来了一个全新的独特机遇——局部100%能量释放,因为Li(n,α)H反应的所有产物都具有高线性能量传递特性。本研究的目的是测定患有B16黑色素瘤的实验动物肿瘤、皮肤、血液、脑和肾中的锂浓度,并分析单次给予300和400mg/kg碳酸锂后锂的潜在毒性。选择碳酸锂是因为其在临床实践中用于治疗精神疾病已有长期经验。采用电感耦合等离子体原子发射光谱法评估组织样本中的锂浓度。在30分钟时间点,锂在肿瘤中的蓄积效率最高(22.4μg/g;剂量为400mg/kg)。尽管肾脏中锂的蓄积量很高,但未发现肾组织的病理变化。因此,锂实际上可用于锂 - 中子俘获疗法的开发,未来研究可使用锂,并按照本研究中测试的锂给药方案对肿瘤细胞进行照射。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f6/9965240/b5868ab6c8db/life-13-00518-g001.jpg

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