Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: Boron concentration correlates with tumor cellularity

Biodistribution of boronophenylalanine in patients with glioblastoma multiforme: Boron concentration correlates with tumor cellularity
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DOI:
10.2307/3579926
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发表时间:
1998-02-01
期刊:
影响因子:
3.4
通讯作者:
Slatkin, DN
Slatkin, DN
中科院分区:
医学3区
文献类型:
--
作者:
Coderre, JA;Chanana, AD;Slatkin, DN

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硼-10(B-10)浓度测定来自15例多形性胶质母细胞瘤患者的107个手术样本,这些患者在手术前静脉输注95原子% B-10富集的对硼苯丙氨酸(BPA)2小时,剂量范围为98至290 mg BPA/kg体重。血液B-10浓度在输注结束时达到最大值(范围为9.3至26.0 μ g B-10/g),并与输注的BPA量成比例。切除的肿瘤样品中的硼浓度在BPA给药剂量范围内为2.7 - 41.3 μ g B-10/g,并且在来自个体患者的多个样品之间以及在相同BPA剂量的患者之间变化很大。组织学切片中的活的肿瘤细胞密度的形态计量学指数与硼浓度呈线性相关,所述组织学切片是从与用于硼分析的肿瘤样品相邻的样品获得的,并且在宏观上与所述肿瘤样品相似。根据该相关性,估计成胶质细胞瘤肿瘤细胞中的B-10浓度比同时的血液B-10浓度高4倍以上。因此,在98至290 mg BPA/kg的剂量范围内,肿瘤细胞中硼的积累是BPA剂量的线性函数,并且在手术获得的肿瘤标本中观察到的硼浓度的变化主要是由于提交用于硼分析的样品中存在的非肿瘤组织(即坏死组织、正常脑)的比例的差异。从该分析中得出的肿瘤:血液B-10浓度比提供了一个基本原理,用于基于BNCT时血液中测得的硼浓度估计硼中子捕获反应导致的活肿瘤细胞的辐射剂量分数,而无需分析个体患者的肿瘤样本。(C)1998年,辐射研究会。
Boron-10 (B-10) concentrations were measured in 107 surgical samples from 15 patients with glioblastoma multiforme who were infused with 95 atom% B-10-enriched p-boronophenylalanine (BPA) intravenously for 2 h just prior to surgery at doses ranging from 98 to 290 mg BPA/kg body weight. The blood B-10 concentration reached a maximum at the end of the infusion (ranging from 9.3 to 26.0 mu g B-10/g) and was proportional to the amount of BPA infused. The boron concentrations in excised tumor samples ranged from 2.7 to 41.3 mu g B-10/g over the range of administered BPA doses and varied considerably among multiple samples from individual patients and among patients at the same BPA dose. A morphometric index of the density of viable-appearing tumor cells in histological sections obtained from samples adjacent to, and macroscopically similar to, the tumor samples used for boron analysis correlated linearly with the boron concentrations. From that correlation it is estimated that B-10 concentrations in glioblastoma tumor cells were over four times greater than concurrent blood B-10 concentrations. Thus, in the dose range of 98 to 290 mg BPA/kg, the accumulation of boron in tumor cells is a linear function of BPA dose and the variations observed in boron concentrations of tumor specimens obtained surgically are largely due to differences in the proportion of nontumor tissue (i.e. necrotic tissue, normal brain) present in the samples submitted for boron analysis. The tumor:blood B-10 concentration ratio derived from this analysis provides a rationale for estimating the fraction of the radiation dose to viable tumor cells resulting from the boron neutron capture reaction based on measured boron concentrations in the blood at the time of BNCT without the need for analysis of tumor samples from individual patients. (C) 1998 by Radiation Research Society.