Bergenheim A Tommy, Capala Jacek, Roslin Michael, Henriksson Roger
Department of Neurosurgery, Umeå University Hospital, Umeå, Sweden.
J Neurooncol. 2005 Feb;71(3):287-93. doi: 10.1007/s11060-004-1724-0.
Boron neutron capture therapy (BNCT) is dependent on the selective accumulation of boron-10 in tumour cells. To maximise the radiation effect, the neutrons should be delivered when the ratio between the boron concentration in tumour cells to that in normal tissues reaches maximum. However, the pharmacokinetics of p-boronophenylalanine (BPA) and other boron delivery agents are only partly known. We used microdialysis to investigate the extracellular in vivo kinetics of boron in three intracerebral compartments -- solid tumour, brain adjacent to tumour (BAT), and the normal brain, as well as the subcutaneous tissue before, during, and after BNCT treatment. The findings were compared to the pharmacokinetics of BPA in the blood. We also measured the glucose metabolism and the levels of glutamate and glycerol in those compartments. Four patients were studied, two patients underwent surgical tumour resection and in two a stereotactic biopsy was performed. The patients were given BPA (900 mg/kg body weight) by a 6-h infusion. The infusion was completed approximately 2-3 h before neutron irradiation. In tumour tissue the extracellular concentration of BPA followed that of blood with a maximal concentration of 31.2 ppm and a maximal ratio vs. blood of 1.07. In BAT, the maximal concentration of BPA was 18.0 ppm with the peak level delayed for 4-6 h compared to the peak in blood with a maximal ratio of 1.2. Maximal blood concentration found was 41.0 ppm. The uptake of BPA in the normal brain was considerably lower than that in the blood and tumour tissue. No change in glucose metabolism was observed. The extracellular level of glycerol was increased after treatment in tumour tissue but not in normal brain suggesting a selective acute cytotoxic effect of BNCT on tumour cells.
硼中子俘获疗法（BNCT）依赖于硼 - 10在肿瘤细胞中的选择性积累。为了使辐射效果最大化，当中肿瘤细胞中硼浓度与正常组织中硼浓度的比值达到最大值时，应输送中子。然而，对 - 硼苯丙氨酸（BPA）和其他硼递送剂的药代动力学仅部分为人所知。我们使用微透析技术研究了在BNCT治疗前、治疗期间和治疗后，三个脑内区域——实体瘤、肿瘤相邻脑组织（BAT）和正常脑，以及皮下组织中硼的细胞外体内动力学。将这些结果与BPA在血液中的药代动力学进行了比较。我们还测量了这些区域的葡萄糖代谢以及谷氨酸和甘油水平。对4名患者进行了研究，其中2名患者接受了肿瘤手术切除，另外2名患者进行了立体定向活检。患者通过6小时输注给予BPA（900毫克/千克体重）。在中子照射前约2 - 3小时完成输注。在肿瘤组织中，BPA的细胞外浓度与血液中的浓度变化趋势一致，最大浓度为31.2 ppm，与血液的最大比值为1.07。在BAT中，BPA的最大浓度为18.0 ppm，峰值水平比血液中的峰值延迟4 - 6小时，最大比值为1.2。测得的血液最大浓度为41.0 ppm。BPA在正常脑中的摄取量明显低于血液和肿瘤组织。未观察到葡萄糖代谢的变化。肿瘤组织中治疗后甘油的细胞外水平升高，但正常脑中未升高，这表明BNCT对肿瘤细胞具有选择性急性细胞毒性作用。
