Haritz D, Gabel D, Huiskamp R
Department of Neurosurgery, University Hospital, Hamburg, Germany.
Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1175-81. doi: 10.1016/0360-3016(94)90492-8.
Within the European collaboration on boron neutron capture therapy (BNCT), a clinical Phase I study is being carried out to establish BNCT as an alternative treatment modality for malignant glioma (WHO III/IV). Data about the pharmacokinetics, biodistribution and toxicity of the boron compound Na2B12H11SH (BSH) are of great importance to avoid radiation damage of healthy tissue and to deliver a sufficient radiation dose.
Twenty four patients suffering from a glioblastoma multiforme entered the study to date, infused with a maximum concentration of up to 50 mg BSH/kg. Boron concentration measurements in tissues, urine, and blood were carried out, using inductively coupled plasma-atomic spectroscopy (ICP-AES) and quantitative neutron capture radiography (QNCR). A cross-calibration of these boron determination techniques was carried out.
In tumor tissue, confirmed by histopathology of small biopsies, we found a consistently high but heterogeneous boron uptake. Necrotic parts contain much lower amounts of boron; normal brain tissue has shown no significant uptake. In skin, bone, muscle, and dura mater only small amounts of boron were found. In blood samples, we found biphasic kinetics, but with variations of the half-lives from patient to patient. The compound is mainly excreted through the urine, but an additional entero-hepatic pathway can be demonstrated. Systematic investigations revealed no toxic side effect of the intravenously administered BSH. Comparable data were obtained by using ICP-AES and QNCR for boron concentration measurements.
Taking into account the radiobiological considerations of the neutron beam source, we found promising facts that BNCT could be a useful irradiation method for highly malignant brain tumors. Favorable amounts of the boron compound BSH were found in tumor tissue, whereas healthy brain tissue has shown no significant uptake.
在欧洲硼中子俘获疗法（BNCT）合作项目中，正在开展一项I期临床研究，以确立BNCT作为恶性胶质瘤（世界卫生组织III/IV级）的一种替代治疗方式。硼化合物Na2B12H11SH（BSH）的药代动力学、生物分布和毒性数据对于避免健康组织受到辐射损伤以及提供足够的辐射剂量至关重要。
迄今为止，24例多形性胶质母细胞瘤患者进入该研究，输注的BSH最大浓度高达50 mg/kg。使用电感耦合等离子体原子光谱法（ICP-AES）和定量中子俘获射线照相术（QNCR）对组织、尿液和血液中的硼浓度进行测量。对这些硼测定技术进行了交叉校准。
在经小活检组织病理学证实的肿瘤组织中，我们发现硼摄取始终很高但不均匀。坏死部分含硼量低得多；正常脑组织未显示出明显摄取。在皮肤、骨骼、肌肉和硬脑膜中仅发现少量硼。在血样中，我们发现了双相动力学，但患者之间半衰期存在差异。该化合物主要通过尿液排泄，但可证明存在额外的肠肝循环途径。系统研究未发现静脉注射BSH有任何毒副作用。使用ICP-AES和QNCR进行硼浓度测量获得了可比数据。
考虑到中子束源的放射生物学因素，我们发现了一些有前景的事实，即BNCT可能是治疗高度恶性脑肿瘤的一种有用的照射方法。在肿瘤组织中发现了适量的硼化合物BSH，而健康脑组织未显示出明显摄取。
