评估一种含新型硼卡醇的非天然氨基酸作为硼递送剂用于F98大鼠胶质瘤中子俘获治疗的效果。
Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma.
作者信息
Futamura Gen, Kawabata Shinji, Nonoguchi Naosuke, Hiramatsu Ryo, Toho Taichiro, Tanaka Hiroki, Masunaga Shin-Ichiro, Hattori Yoshihide, Kirihata Mitsunori, Ono Koji, Kuroiwa Toshihiko, Miyatake Shin-Ichi
机构信息
Department of Neurosurgery, Osaka Medical College, 2-7 Daigakumachi, Takatuki-shi, Osaka, Japan.
Kyoto university research reactor institute, 2, Asahiro-Nishi, Kumatori-cho, Sennan-gun, Osaka, Japan.
出版信息
Radiat Oncol. 2017 Jan 23;12(1):26. doi: 10.1186/s13014-017-0765-4.
BACKGROUND
Boron neutron capture therapy (BNCT) is a unique particle radiation therapy based on the nuclear capture reactions in boron-10. We developed a novel boron-10 containing sodium borocaptate (BSH) derivative, 1-amino-3-fluorocyclobutane-1-carboxylic acid (ACBC)-BSH. ACBC is a tumor selective synthetic amino acid. The purpose of this study was to assess the biodistribution of ACBC-BSH and its therapeutic efficacy following Boron Neutron Capture Therapy (BNCT) of the F98 rat glioma.
METHODS
We evaluated the biodistribution of three boron-10 compounds, ACBC-BSH, BSH and boronophenylalanine (BPA), in vitro and in vivo, following intravenous (i.v.) administration and intratumoral (i.t.) convection-enhanced delivery (CED) in F98 rat glioma bearing rats. For BNCT studies, rats were stratified into five groups: untreated controls, neutron-irradiation controls, BNCT with BPA/i.v., BNCT with ACBC-BSH/CED, and BNCT concomitantly using BPA/i.v. and ACBC-BSH/CED.
RESULTS
In vitro, ACBC-BSH attained higher cellular uptake F98 rat glioma cells compared with BSH. In vivo biodistribution studies following i.v. administration and i.t. CED of ACBC-BSH attained significantly higher boron concentrations than that of BSH, but much lower than that of BPA. However, following convection enhanced delivery (CED), ACBC-BSH attained significantly higher tumor concentrations than BPA. The i.t. boron-10 concentrations were almost equal between the ACBC-BSH/CED group and BPA/i.v. group of rats. The tumor/brain boron-10 concentration ratio was higher with ACBC-BSH/CED than that of BPA/i.v. group. Based on these data, BNCT studies were carried out in F98 glioma bearing rats using BPA/i.v. and ACBC-BSH/CED as the delivery agents. The corresponding mean survival times were 37.4 ± 2.6d and 44.3 ± 8.0d, respectively, and although modest, these differences were statistically significant.
CONCLUSIONS
Our findings suggest that further studies are warranted to evaluate ACBC-BSH/CED as a boron delivery agent.
背景
硼中子俘获疗法（BNCT）是一种基于硼 - 10核俘获反应的独特粒子放射疗法。我们研发了一种新型含硼 - 10的硼卡酸钠（BSH）衍生物，即1 - 氨基 - 3 - 氟环丁烷 - 1 - 羧酸（ACBC） - BSH。ACBC是一种肿瘤选择性合成氨基酸。本研究的目的是评估ACBC - BSH在F98大鼠胶质瘤硼中子俘获疗法（BNCT）后的生物分布及其治疗效果。
方法
我们评估了三种硼 - 10化合物，即ACBC - BSH、BSH和硼苯丙氨酸（BPA），在荷F98大鼠胶质瘤的大鼠静脉注射（i.v.）和瘤内（i.t.）对流增强递送（CED）后的体内外生物分布。对于BNCT研究，将大鼠分为五组：未治疗对照组、中子照射对照组、BPA/i.v.的BNCT组、ACBC - BSH/CED的BNCT组以及同时使用BPA/i.v.和ACBC - BSH/CED的BNCT组。
结果
在体外，与BSH相比，ACBC - BSH在F98大鼠胶质瘤细胞中的摄取量更高。静脉注射和瘤内CED后ACBC - BSH的体内生物分布研究表明，其硼浓度显著高于BSH，但远低于BPA。然而，在对流增强递送（CED）后，ACBC - BSH的肿瘤浓度显著高于BPA。ACBC - BSH/CED组和BPA/i.v.组大鼠的瘤内硼 - 10浓度几乎相等。ACBC - BSH/CED组的肿瘤/脑硼 - 10浓度比高于BPA/i.v.组。基于这些数据，在荷F98胶质瘤的大鼠中使用BPA/i.v.和ACBC - BSH/CED作为递送剂进行了BNCT研究。相应的平均生存时间分别为37.4±2.6天和44.3±8.0天，尽管差异不大，但具有统计学意义。
结论
我们的研究结果表明，有必要进一步研究评估ACBC - BSH/CED作为硼递送剂的效果。
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