Boron neutron capture therapy using dodecaborated albumin conjugates with maleimide is effective in a rat glioma model
Boron neutron capture therapy using dodecaborated albumin conjugates with maleimide is effective in a rat glioma model
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DOI：
10.1007/s10637-021-01201-7
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发表时间：
2021-11-24
影响因子：
3.4
通讯作者：
Wanibuchi, Masahiko
中科院分区：
文献类型：
--
作者：
Kashiwagi, Hideki;Kawabata, Shinji;Wanibuchi, Masahiko
引言硼中子捕获疗法（BNCT）是一种具有生物学靶向的细胞选择性颗粒辐照疗法，利用硼和中子的核捕获反应。最近，加速器中子发电机已用于临床环境中，并且对开发新硼化合物的期望正在增长。在这项研究的方法和结果中，我们专注于血清白蛋白，这是一种众所周知的药物输送系统，并开发了MaleImide官能化的封闭闭合闭合白蛋白共轭（MID-AC）作为BORON携带BNCT的携带系统。我们的生物分布实验涉及含有F98胶质瘤的大鼠脑肿瘤模型，该模型系统地使用了MID-AC，并且表现出硼的积累和长期保留。与对照组相比，我们对MID-AC的BNCT研究观察到生存率的统计学显着延长，其结果与BNCT研究的结果可与硼苯基丙氨酸（BPA）相当，这是临床环境中的标准用途。每个中位生存时间如下：未经治疗的对照组； 24.5天，中子辐照对照组； 24.5天，BPA静脉内给药（i.v.）终止后2.5小时后的中子照射； 31.5天，以及静脉内终止后2.5或24小时后的中子照射。 Mid-Ac;分别为33.5或33.0天。根据这些生存时间估算了F98大鼠胶质瘤中MID-AC的生物学有效性因子，并发现该趋势高至12。在MID-AC给药后24小时内确认了这种趋势。结论MID-AC诱导有效的硼中子捕获反应，因为MID-AC中包含的白蛋白保留在肿瘤中，并且具有很大的潜力，可以成为BNCT治疗高级神经胶质瘤的有效递送系统。
Introduction Boron neutron capture therapy (BNCT) is a biologically targeted, cell-selective particle irradiation therapy that utilizes the nuclear capture reaction of boron and neutron. Recently, accelerator neutron generators have been used in clinical settings, and expectations for developing new boron compounds are growing. Methods and Results In this study, we focused on serum albumin, a well-known drug delivery system, and developed maleimide-functionalized closo-dodecaborate albumin conjugate (MID-AC) as a boron carrying system for BNCT. Our biodistribution experiment involved F98 glioma-bearing rat brain tumor models systemically administered with MID-AC and demonstrated accumulation and long retention of boron. Our BNCT study with MID-AC observed statistically significant prolongation of the survival rate compared to the control groups, with results comparable to BNCT study with boronophenylalanine (BPA) which is the standard use of in clinical settings. Each median survival time was as follows: untreated control group; 24.5 days, neutron-irradiated control group; 24.5 days, neutron irradiation following 2.5 h after termination of intravenous administration (i.v.) of BPA; 31.5 days, and neutron irradiation following 2.5 or 24 h after termination of i.v. of MID-AC; 33.5 or 33.0 days, respectively. The biological effectiveness factor of MID-AC for F98 rat glioma was estimated based on these survival times and found to be higher to 12. This tendency was confirmed in BNCT 24 h after MID-AC administration. Conclusion MID-AC induces an efficient boron neutron capture reaction because the albumin contained in MID-AC is retained in the tumor and has a considerable potential to become an effective delivery system for BNCT in treating high-grade gliomas.