Boron Neutron Capture Therapy of Brain Tumors: Biodistribution, Pharmacokinetics, and Radiation Dosimetry of Sodium Borocaptate in Patients with Gliomas

医学 药代动力学 体内分布 核医学 胶质瘤 间变性星形细胞瘤 脑瘤 人口 放射治疗 星形细胞瘤 病理 内科学 体内 癌症研究 生物技术 环境卫生 生物
作者
Joseph H. Goodman,Weilian Yang,Rolf F. Barth,Zhixian Gao,Carl P. Boesel,Alfred E. Staubus,Nilendu Gupta,R. Gahbauer,Dianne M. Adams,Christopher R. Gibson,Amy K. Ferketich,Melvin L. Moeschberger,Mark S. Soloway,David E. Carpenter,Brent J. Albertson,William F. Bauer,Mao Zhi Zhang,Chung Cheng Wang
出处
期刊:Neurosurgery [Lippincott Williams & Wilkins]
卷期号:47 (3): 608-622 被引量:62
标识
DOI:10.1097/00006123-200009000-00016
摘要

ABSTRACT OBJECTIVE The purpose of this study was to obtain tumor and normal brain tissue biodistribution data and pharmacokinetic profiles for sodium borocaptate (Na2B12H11SH) (BSH), a drug that has been used clinically in Europe and Japan for boron neutron capture therapy of brain tumors. The study was performed with a group of 25 patients who had preoperative diagnoses of either glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) and were candidates for debulking surgery. Nineteen of these patients were subsequently shown to have histopathologically confirmed diagnoses of GBM or AA, and they constituted the study population. METHODS BSH (non-10 B-enriched) was infused intravenously, in a 1-hour period, at doses of 15, 25, and 50 mg boron/kg body weight (corresponding to 26.5, 44.1, and 88.2 mg BSH/kg body weight, respectively) to groups of 3, 3, and 13 patients, respectively. Multiple samples of tumor tissue, brain tissue around the tumors, and normal brain tissue were obtained at either 3 to 7 or 13 to 15 hours after infusion. Blood samples for pharmacokinetic studies were obtained at times up to 120 hours after termination of the infusion. Sixteen of the patients underwent surgery at the Beijing Neurosurgical Institute and three at The Ohio State University, where all tissue samples were subsequently analyzed for boron content by direct current plasma-atomic emission spectroscopy. RESULTS Blood boron values peaked at the end of the infusion and then decreased triexponentially during the 120-hour sampling period. At 6 hours after termination of the infusion, these values had decreased to 20.8, 29.1, and 62.6 μg/ml for boron doses of 15, 25, and 50 mg/kg body weight, respectively. For a boron dose of 50 mg/kg body weight, the maximum (mean ± standard deviation) solid tumor boron values at 3 to 7 hours after infusion were 17.1 ± 5.8 and 17.3 ± 10.1 μg/g for GBMs and AAs, respectively, and the mean tumor value averaged across all samples was 11.9 μg/g for both GBMs and AAs. In contrast, the mean normal brain tissue values, averaged across all samples, were 4.6 ± 5.1 and 5.5 ± 3.9 μg/g and the tumor/normal brain tissue ratios were 3.8 and 3.2 for patients with GBMs and AAs, respectively. The large standard deviations indicated significant heterogeneity in uptake in both tumor and normal brain tissue. Regions histopathologically classified either as a mixture of tumor and normal brain tissue or as infiltrating tumor exhibited slightly lower boron concentrations than those designated as solid tumor. After a dose of 50 mg/kg body weight, boron concentrations in blood decreased from 104 μg/ml at 2 hours to 63 μg/ml at 6 hours and concentrations in skin and muscle were 43.1 and 39.2 μg/g, respectively, during the 3- to 7-hour sampling period. CONCLUSION When tumor, blood, and normal tissue boron concentrations were taken into account, the most favorable tumor uptake data were obtained with a boron dose of 25 mg/kg body weight, 3 to 7 hours after termination of the infusion. Although blood boron levels were high, normal brain tissue boron levels were almost always lower than tumor levels. However, tumor boron concentrations were less than those necessary for boron neutron capture therapy, and there was significant intratumoral and interpatient variability in the uptake of BSH, which would make estimation of the radiation dose delivered to the tumor very difficult. It is unlikely that intravenous administration of a single dose of BSH would result in therapeutically useful levels of boron. However, combining BSH with boronophenylalanine, the other compound that has been used clinically, and optimizing their delivery could increase tumor boron uptake and potentially improve the efficacy of boron neutron capture therapy.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
鲸落发布了新的文献求助30
1秒前
葳葳完成签到,获得积分10
3秒前
sl发布了新的文献求助10
6秒前
6秒前
sanqian911完成签到,获得积分10
7秒前
昏睡的蟠桃应助liars采纳,获得150
8秒前
斯文败类应助荒野风采纳,获得10
8秒前
8秒前
hrzmlily完成签到,获得积分10
10秒前
顽主完成签到,获得积分10
11秒前
义气访曼完成签到 ,获得积分10
12秒前
时尚战斗机完成签到,获得积分10
12秒前
14秒前
亦玉完成签到,获得积分10
14秒前
Philadelphus完成签到,获得积分20
16秒前
16秒前
wsh完成签到 ,获得积分10
17秒前
luyue9406完成签到,获得积分10
17秒前
luochen完成签到,获得积分10
17秒前
酷波er应助奶黄包采纳,获得10
18秒前
ROMANTIC完成签到 ,获得积分10
18秒前
Hancock完成签到 ,获得积分10
19秒前
luyue9406发布了新的文献求助10
20秒前
Akim应助小王采纳,获得10
20秒前
甜蜜的楷瑞应助zqfxc采纳,获得10
22秒前
Hello应助花雨落123采纳,获得10
24秒前
25秒前
26秒前
柚仝完成签到 ,获得积分10
26秒前
贾明灵完成签到,获得积分10
26秒前
未来学术司马懿应助LIUYONG采纳,获得10
27秒前
Dops完成签到,获得积分10
29秒前
票子发布了新的文献求助10
30秒前
晚风完成签到 ,获得积分10
30秒前
坚强莺发布了新的文献求助10
30秒前
无奈曼云完成签到,获得积分10
31秒前
不会吹口哨完成签到,获得积分10
31秒前
易槐完成签到,获得积分10
32秒前
情怀应助和谐的梦蕊采纳,获得10
32秒前
33秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038426
求助须知:如何正确求助?哪些是违规求助? 3576119
关于积分的说明 11374556
捐赠科研通 3305834
什么是DOI,文献DOI怎么找? 1819339
邀请新用户注册赠送积分活动 892678
科研通“疑难数据库(出版商)”最低求助积分说明 815029