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含硼苯丙氨酸的十二硼酸盐在大鼠脑肿瘤模型中用于硼中子俘获治疗的疗效

The Therapeutic Effects of Dodecaborate Containing Boronophenylalanine for Boron Neutron Capture Therapy in a Rat Brain Tumor Model.

作者信息

Fukuo Yusuke, Hattori Yoshihide, Kawabata Shinji, Kashiwagi Hideki, Kanemitsu Takuya, Takeuchi Koji, Futamura Gen, Hiramatsu Ryo, Watanabe Tsubasa, Hu Naonori, Takata Takushi, Tanaka Hiroki, Suzuki Minoru, Miyatake Shin-Ichi, Kirihata Mitsunori, Wanibuchi Masahiko

机构信息

Department of Neurosurgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-shi, Osaka 569-8686, Japan.

Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, 1-1 Gakuen-cho, Nakaku, Sakai-shi, Osaka 599-8531, Japan.

出版信息

Biology (Basel). 2020 Dec 1;9(12):437. doi: 10.3390/biology9120437.

Abstract

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.

摘要

背景

开发有效的硼化合物是硼中子俘获疗法(BNCT)研究的一个主要领域。我们制备了一种新型硼化合物——硼苯丙氨酸 - 酰胺烷基十二硼酸盐(BADB),用于BNCT,并着重研究其对大鼠脑肿瘤模型的影响。

方法

评估了F98大鼠胶质瘤细胞在暴露于硼苯丙氨酸(BPA,目前临床正在使用)和BADB后的硼浓度,并评估了它们在荷F98胶质瘤大鼠体内的生物分布。在中子辐照研究中,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

用BPA和BADB辐照的组的存活分数没有显著差异。在对流增强给药终止后6小时给予BADB可确保肿瘤中硼浓度最高(45.8μg硼/克)。BADB与BPA联合组的中位生存时间比BPA组显示出更显著的生存延长。

结论

BADB是一种用于BNCT的新型硼化合物,可使接受BNCT的患者产生延长的生存效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d22d/7759915/4c25141a965d/biology-09-00437-g0A1.jpg

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