Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS).
Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS).
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DOI：
10.1111/jmi.12126
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发表时间：
2014-06
影响因子：
2
通讯作者：
Kabalka GW
中科院分区：
文献类型：
--
作者：
Chandra S;Ahmad T;Barth RF;Kabalka GW
肿瘤的硼中子俘获治疗（BNCT）依赖于选择性地将足够数量的硼-10（10 B）原子递送到单个肿瘤细胞。如果肿瘤细胞中存在足够数量的10 B原子，则10 B（n，α）7 Li中子捕获和裂变反应会导致细胞杀伤。核内10 B定位通过损伤DNA增强细胞杀伤的效率。10 B原子的净细胞含量反映了单个肿瘤细胞中结合和游离的硼池。目前无法通过临床适用的技术（如PET和MRI）以亚细胞尺度分辨率对硼递送剂递送的这些池进行评估。在这项研究中，二次离子质谱（西姆斯）为基础的成像仪器，CAMECA IMS 3f离子显微镜，能够500 nm的空间分辨率。评价低温制备的培养的人T98 G胶质母细胞瘤细胞对两种递送剂的硼摄取和保留。第一种是L-对硼苯丙氨酸（BPA），已在临床上用于高级别胶质瘤、头颈部复发性肿瘤和黑色素瘤的BNCT。第二，硼类似物的非天然氨基酸，1-氨基-3-borono-cyclopentanecarboxylic acid（顺ABCPC），已在啮齿动物神经胶质瘤和黑色素瘤模型中进行了研究，通过定量硼在细胞核和细胞质中的个别肿瘤细胞。通过将细胞暴露于无硼营养培养基来评估硼的结合池和游离池。BPA和顺式ABCPC都以游离或松散结合的形式向人胶质母细胞瘤细胞的细胞核和细胞质提供了几乎70%的硼。这种游离的硼可以很容易地从细胞中移动出来，并与细胞外的硼处于某种平衡状态。在BPA的情况下，硼的细胞内游离池也受到营养培养基中苯丙氨酸存在的影响。这表明，它可能是有利的，如果患者被放置在低苯丙氨酸饮食开始BNCT之前。由于BPA目前在临床上用于BNCT，我们的观察结果可能与未来使用该药物的临床研究直接相关，并为个性化治疗计划方案提供支持，而不是使用固定的BPA输注方案。
Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 (10B) atoms to individual tumor cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumor cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B atoms reflects both bound and free pools of boron in individual tumor cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular scale resolution by clinically applicable techniques such as PET and MRI. In this study, secondary ion mass spectrometry (SIMS) based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high grade gliomas, recurrent tumors of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumor cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a low phenylalanine diet prior to the initiation of BNCT. Since BPA currently is used clinically for BNCT, our observations may have direct relevance to future clinical studies utilizing this agent and provides support for individualized treatment planning regimens rather than the use of fixed BPA infusion protocols.
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影响因子：
7.4
作者：
AUSSERER, WA;LING, YC;MORRISON, GH
通讯作者：
MORRISON, GH
影响因子：
2
作者：
CHANDRA, S;MORRISON, GH;WOLCOTT, CC
通讯作者：
WOLCOTT, CC
影响因子：
1.6
作者：
Kabalka, G. W.;Yao, M. -L.;Chandra, S.
通讯作者：
Chandra, S.
影响因子：
7.4
作者：
Chandra, S;Smith, DR;Morrison, GH
通讯作者：
Morrison, GH
影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN