Elowitz E H, Bergland R M, Coderre J A, Joel D D, Chadha M, Chanana A D
Department of Neurosurgery, Beth Israel Medical Center, New York, New York 10128, USA.
Neurosurgery. 1998 Mar;42(3):463-8; discussion 468-9. doi: 10.1097/00006123-199803000-00004.
The success of boron neutron capture therapy depends on the safety and specificity of the boron delivery agent. As a preface to clinical boron neutron capture therapy of glioblastoma multiforme, a biodistribution study of intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for resection of glioblastoma was performed.
Varying doses of intravenously administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given to patients 2 to 3 hours prior to the start of craniotomy for either suspected or known glioblastoma multiforme. Blood samples were collected over a 48-hour period for boron assay. At surgery, multiple samples of tumor, brain, and scalp were obtained for boron and histological analysis.
Seventeen patients were studied; all but one had glioblastoma multiforme. No adverse effects from the BPA infusions were noted. The boron concentration in the blood reached a maximum at the end of the BPA infusion and was proportional to the administered dose of BPA. Normal brain concentrations of boron generally were equal to or less than that in blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/- standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA uptake in glioblastoma samples appears to correlate with the degree of cellularity observed on histological examination.
Intravenous BPA administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake in surgical samples of glioblastoma tissue is variable and may depend on the fraction of viable tumor cells in the individual sample. Further clinical studies using BPA as a boron delivery agent for boron neutron capture therapy of glioblastoma multiforme appear warranted.
硼中子俘获疗法的成功取决于硼递送剂的安全性和特异性。作为多形性胶质母细胞瘤临床硼中子俘获疗法的前言，对因多形性胶质母细胞瘤行开颅手术切除的患者进行了静脉注射对硼苯丙氨酸（BPA）的生物分布研究。
在疑似或已知多形性胶质母细胞瘤患者开颅手术开始前2至3小时，静脉给予不同剂量的BPA-果糖（每千克体重130 - 250毫克BPA）。在48小时内采集血样进行硼含量测定。手术时，获取肿瘤、脑和头皮的多个样本进行硼含量及组织学分析。
研究了17例患者；除1例外均为多形性胶质母细胞瘤。未观察到BPA输注的不良反应。血液中的硼浓度在BPA输注结束时达到最高，且与BPA给药剂量成正比。正常脑组织中的硼浓度一般等于或低于血液中的硼浓度。肿瘤与血液的硼比值变化很大：1.6±0.8（平均值±标准差；n = 187；范围为0.3 - 3.5）。在多形性胶质母细胞瘤样本中观察到的BPA摄取异质性似乎与组织学检查中观察到的细胞密度程度相关。
静脉注射高达250毫克/千克剂量的BPA是安全且耐受性良好的。多形性胶质母细胞瘤组织手术样本中的BPA摄取存在差异，可能取决于单个样本中存活肿瘤细胞的比例。使用BPA作为硼中子俘获疗法治疗多形性胶质母细胞瘤的硼递送剂的进一步临床研究似乎是必要的。
