Uptakes of boronophenylalanine in the in vitro and in situ glioblastoma and the potential efficacy of boron neutron capture therapy

IF 2 Q3 NEUROSCIENCES
Shining Zhang , Yujie Wei , Wenjiao Gu , Shuangyi Li , Ting Liu , Limei Shuai , Yu Tang , Ying Jiang , Xiaochun Zhou , Yucai Wei , Guan Wang , Long Gu , Yumin Li , Futian Tang , Daiying Zuo
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Abstract

Human glioblastoma (GBM) is the most malignant brain tumor. Boron neutron capture therapy (BNCT) is proved to be a new technology for the effective treatment of GBM. We previously reported that boronophenylalanine (BPA), the boron drug used in BNCT prefers to the tumor of a mouse subcutaneous tumor model injected U87 and GL261, two GBM cell lines. The present study was designed to investigate the distribution of BPA in the tumor of a mouse in situ brain tumor model injected U87 and GL261 in the brain. The tumor model was evaluated by using small animal magnetic resonance imaging (MRI) and confirmed with the morphological observations. The boron concentration indicative of BPA in cells and tumor was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results revealed that the protein of L-type amino acid transporter (LAT1) was highly expressed in both U87 and GL261 cells. In addition, boron concentration in U87 and GL261 cells was increased 1, 2, 3, 5 and 7 h after addition of BPA in a time-dependently manner. However, the boron concentration in the cells was rapidly decreased when the BPA in the medium was withdrawn for 1 h at each time point, reaching almost the same levels between the time points. In one mouse in situ brain tumor model injected U87 cells, the concentration of boron in the tumor tissue (25.529 μg/g) was higher than that in brain tissue (8.973 μg/g), blood (11.407 μg/g), heart (13.131 μg/g), liver (11.271 μg/g), spleen (15.631 μg/g) and lung (16.226 μg/g) respectively, having ratios of tumor/normal tissue 2.845, 2.238, 1.944, 2.265, 1.633 and 1.537 respectively. Similarly, in another mouse in situ brain tumor model injected GL261 cells, the concentration of boron in the tumor tissue (23.039 μg/g) was higher than that in brain tissue (8.141 μg/g), blood (9.573 μg/g), heart (12.119 μg/g), liver (9.609 μg/g), spleen (15.852 μg/g) and lung (12.565 μg/g) respectively, having ratios of tumor/normal tissue 2.831, 2.407, 1.901, 2.398, 1.453 and 1.834 respectively. The results suggest that uptakes of BPA in two cell lines occur in a time-dependent manner and that BPA preferred to distribute in brain tumor tissue than other normal tissues, having potential efficacy of BNCT.
体外和原位胶质母细胞瘤对硼苯丙氨酸的摄取及硼中子俘获治疗的潜在疗效
人胶质母细胞瘤(GBM)是恶性程度最高的脑肿瘤。硼中子俘获治疗(BNCT)是一种有效治疗GBM的新技术。我们之前报道了BNCT中使用的硼药物硼苯丙氨酸(BPA)对注射了两种GBM细胞系U87和GL261的小鼠皮下肿瘤模型的肿瘤有偏向性。本研究旨在研究U87和GL261在小鼠原位脑瘤模型脑内的分布情况。采用小动物磁共振成像(MRI)对肿瘤模型进行评价,并结合形态学观察对其进行验证。采用电感耦合等离子体原子发射光谱(ICP-AES)测定了细胞和肿瘤中指示BPA的硼浓度。结果显示,l型氨基酸转运蛋白LAT1在U87和GL261细胞中均有高表达。此外,添加BPA后U87和GL261细胞中的硼浓度分别在1、2、3、5和7 h呈时间依赖性增加。然而,当每个时间点提取培养基中的BPA 1 h时,细胞中的硼浓度迅速下降,在时间点之间达到几乎相同的水平。在注射U87细胞的小鼠原位脑肿瘤模型中,肿瘤组织中硼的浓度(25.529 μg/g)高于脑组织(8.973 μg)、血液(11.407 μg/g)、心脏(13.131 μg/g)、肝脏(11.271 μg)、脾脏(15.631 μg)和肺(16.226 μg/g),其与正常组织的比值分别为2.845、2.238、1.944、2.265、1.633和1.537。同样,在注射GL261细胞的另一小鼠原位脑肿瘤模型中,肿瘤组织中硼的浓度(23.039 μg/g)高于脑组织(8.141 μg)、血液(9.573 μg/g)、心脏(12.119 μg/g)、肝脏(9.609 μg)、脾脏(15.852 μg/g)和肺(12.565 μg/g),其与正常组织的比值分别为2.831、2.407、1.901、2.398、1.453和1.834。结果表明,双酚a在两种细胞系中的吸收具有时间依赖性,双酚a更倾向于分布在脑肿瘤组织中,而不是其他正常组织,具有BNCT的潜在功效。
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来源期刊
IBRO Neuroscience Reports
IBRO Neuroscience Reports Neuroscience-Neuroscience (all)
CiteScore
2.80
自引率
0.00%
发文量
99
审稿时长
14 weeks
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