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注射L-对硼苯丙氨酸和硼卡钠后B在胶质瘤原位异种移植小鼠模型中的生物分布

Biodistribution of B in Glioma Orthotopic Xenograft Mouse Model after Injection of L-para-Boronophenylalanine and Sodium Borocaptate.

作者信息

Gubanova Natalya V, Tsygankova Alphiya R, Zavjalov Evgenii L, Romashchenko Alexander V, Orlov Yuriy L

机构信息

Institute of Cytology and Genetics, Siberian Branch Russian Academy of Sciences, 630090 Novosibirsk, Russia.

Nikolaev Institute of Inorganic Chemistry, Siberian Branch Russian Academy of Sciences, 630090 Novosibirsk, Russia.

出版信息

Biomedicines. 2021 Jun 23;9(7):722. doi: 10.3390/biomedicines9070722.

Abstract

Boron neutron capture therapy (BNCT) is based on the ability of the boron-10 (B) isotope to capture epithermal neutrons, as a result of which the isotope becomes unstable and decays into kinetically active elements that destroy cells where the nuclear reaction has occurred. The boron-carrying compounds-L-para-boronophenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH)-have low toxicity and, today, are the only representatives of such compounds approved for clinical trials. For the effectiveness and safety of BNCT, a low boron content in normal tissues and substantially higher content in tumor tissue are required. This study evaluated the boron concentration in intracranial grafts of human glioma U87MG cells and normal tissues of the brain and other organs of mice at 1, 2.5 and 5 h after administration of the boron-carrying compounds. A detailed statistical analysis of the boron biodistribution dynamics was performed to find a 'window of opportunity' for BNCT. The data demonstrate variations in boron accumulation in different tissues depending on the compound used, as well as significant inter-animal variation. The protocol of administration of BPA and BSH compounds used did not allow achieving the parameters necessary for the successful course of BNCT in a glioma orthotopic xenograft mouse model.

摘要

硼中子俘获疗法(BNCT)基于硼 - 10(B)同位素捕获超热中子的能力,由此该同位素变得不稳定并衰变成具有动力学活性的元素,这些元素会破坏发生核反应的细胞。携带硼的化合物——L - 对硼苯丙氨酸(BPA)和巯基十一氢 - 闭式 - 十二硼酸钠(BSH)——毒性较低,且目前是仅有的被批准用于临床试验的此类化合物。为实现BNCT的有效性和安全性,需要正常组织中的硼含量低,而肿瘤组织中的硼含量要高得多。本研究评估了在给予携带硼的化合物后1小时、2.5小时和5小时,人胶质瘤U87MG细胞颅内移植瘤以及小鼠脑和其他器官的正常组织中的硼浓度。对硼生物分布动态进行了详细的统计分析,以找到BNCT的“机会窗口”。数据表明,根据所使用的化合物不同,硼在不同组织中的积累存在差异,并且动物个体之间也存在显著差异。在胶质瘤原位异种移植小鼠模型中,所使用的BPA和BSH化合物给药方案无法实现BNCT成功实施所需的参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dbd/8301403/09a141f9973a/biomedicines-09-00722-g001.jpg

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