The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model.
The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model.
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DOI：
10.3390/biology9120437
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发表时间：
2020-12-01
期刊：
影响因子：
4.2
通讯作者：
Wanibuchi M
中科院分区：
文献类型：
--
作者：
Fukuo Y;Hattori Y;Kawabata S;Kashiwagi H;Kanemitsu T;Takeuchi K;Futamura G;Hiramatsu R;Watanabe T;Hu N;Takata T;Tanaka H;Suzuki M;Miyatake SI;Kirihata M;Wanibuchi M
本文报道了一种用于硼中子俘获治疗（BNCT）的新型硼化合物，命名为十二烷硼酸硼苯丙氨酸酰胺（BADB）。它的特点是每个分子中含有大量的10 B，连接硼苯丙氨酸（BPA）和十二硼酸酯，我们对其功效进行了各种实验。它在细胞水平的高积累使其成为一种有前途的新药，但当静脉给药时，它在脑肿瘤组织中没有充分积累。然而，在中子照射实验中，该药物显示出显着的高复合生物学效应，并显着延长大鼠脑肿瘤模型的生存时间。我们证实了BADB在BNCT中的抗肿瘤疗效以及与BPA联合给药时的额外疗效。虽然这种药物作为单一药物给药时效果不佳，但当与BPA联合给药时，它上级BPA单独给药，使其成为我们在临床实践中一直在等待的药物。背景：开发有效的硼化合物是硼中子俘获疗法（BNCT）研究的一个主要研究领域。我们创造了一种新的硼化合物，boronophenylalanine-amide alkyl dodecaborate（BADB），用于BNCT，并重点阐明它如何影响大鼠脑肿瘤模型。研究方法：评价了暴露于硼苯丙氨酸（BPA）（目前正在临床上使用）和BADB后F98大鼠胶质瘤细胞的硼浓度，并评估了F98胶质瘤荷瘤大鼠的生物分布。在中子照射研究中，根据生存时间评估了每种硼化合物的体外细胞毒性和体内相应的治疗效果。结果：BPA和BADB照射组的存活分数无显著性差异。对流增强输送终止后给予BADB 6小时，确保肿瘤中的最高硼浓度（45.8 μg B/g）。BADB联合BPA组的中位生存时间比BPA组更明显延长。结论：BADB是BNCT的一种新型硼化合物，可延长接受BNCT患者的生存期。
We have developed a new boron compound for application in boron neutron capture therapy (BNCT) named boronophenylalanine–amide alkyl dodecaborate (BADB). It is characterized by a larger amount of 10B per molecule, linking boronphenylalanine (BPA) and dodecaborate, and we conducted various experiments on its efficacy. Its high accumulation at the cellular level made it a promising novel drug, but it did not sufficiently accumulate in brain tumor tissue when intravenously administered. However, in neutron irradiation experiments, the drug showed remarkably high compound biological effectiveness and significantly prolonged the survival time in rat brain tumor models. We confirmed the antitumor efficacy of BADB in BNCT and its additional efficacy when administered in combination with BPA. Though this drug showed poor results when administered as a single agent, it was superior to BPA alone when administered in combination with BPA, making it a drug that we have been waiting for in our clinical practice. Background: The development of effective boron compounds is a major area of research in the study of boron neutron capture therapy (BNCT). We created a novel boron compound, boronophenylalanine–amide alkyl dodecaborate (BADB), for application in BNCT and focused on elucidating how it affected a rat brain tumor model. Methods: The boron concentration of F98 rat glioma cells following exposure to boronophenylalanine (BPA) (which is currently being utilized clinically) and BADB was evaluated, and the biodistributions in F98 glioma-bearing rats were assessed. In neutron irradiation studies, the in vitro cytotoxicity of each boron compound and the in vivo corresponding therapeutic effect were evaluated in terms of survival time. Results: The survival fractions of the groups irradiated with BPA and BADB were not significantly different. BADB administered for 6 h after the termination of convection-enhanced delivery ensured the highest boron concentration in the tumor (45.8 μg B/g). The median survival time in the BADB in combination with BPA group showed a more significant prolongation of survival than that of the BPA group. Conclusion: BADB is a novel boron compound for BNCT that triggers a prolonged survival effect in patients receiving BNCT.
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影响因子：
5.6
作者：
Matsuura M;Ohshima M;Hiruta Y;Nishimura T;Nagase K;Kanazawa H
通讯作者：
Kanazawa H
影响因子：
3.9
作者：
Kawabata S;Yang W;Barth RF;Wu G;Huo T;Binns PJ;Riley KJ;Ongayi O;Gottumukkala V;Vicente MG
通讯作者：
Vicente MG
影响因子：
10.8
作者：
Maruyama, K;Ishida, O;Yanagie, H
通讯作者：
Yanagie, H
DOI：
10.1016/0360-3016(92)90951-d
发表时间：
1994-10-15
影响因子：
7
作者：
CODERRE, JA;BUTTON, TM;LIU, HB
通讯作者：
LIU, HB
影响因子：
2
作者：
Kawabata, Shinji;Miyatake, Shin-Ichi;Ono, Koji
通讯作者：
Ono, Koji