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Boron delivery agents for neutron capture therapy of cancer

Cancer Communications 2018年第1期38卷 371-385页

作者： rolf f.barth Peng Mi Weilian Yang Department of Pathology The Ohio State University4132 Graves Hall333 W.10th AveColumbusOH 43210USA Department of Radiology Center for Medical ImagingState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for BiotherapyChengduSichuan 610041P.R.China Present Address:Neurosurgery and Brain and Nerve Research Laboratory The First Affiliated Hospital of Suzhou UniversitySuzhouJiangsu 215004P.R.China

Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope,boron-10,is irradiated with neutrons to produce high energy alpha *** review will focus on tumor-targeting boron delivery agents that are an essential component of this binary *** low molecular weight boron-containing drugs currently are being used clinically,boronopheny-lalanine(BPA)and sodium borocaptate(BSH).Although they are far from being ideal,their therapeutic efficacy has been demonstrated in patients with high grade gliomas,recurrent tumors of the head and neck region,and a much smaller number with cutaneous and extra-cutaneous *** of their limitations,great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical *** include boron-containing porphyrins,amino acids,polyamines,nucleosides,peptides,monoclonal antibodies,liposomes,nanoparticles of various types,boron cluster compounds and ***-rently,however,none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution ***,at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH,either alone or in combination,with the hope that future research will identify new and better boron delivery agents for clinical use.

关键词： Boron delivery agents Neutron capture therapy Brain tumors Head and neck cancer Melanoma

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Evaluation of sodium borocaptate(BSH)and boronophenylalanine(BPA)as boron delivery agents for neutron capture therapy(NCT)of cancer:an update and a guide for the future clinical evaluation of new boron delivery agents for NCT

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Cancer Communications 2024年第8期44卷 893-909页

作者： rolf f.barth Nilendu Gupta Shinji Kawabata Department of Pathology The Ohio State UniversityColumbusOhioUSA Department of Radiation Oncology The Ohio State UniversityColumbusOhioUSA Department of Neurosurgery Osaka Medical and Pharmaceutical UniversityTakatsukiOsakaJapan

Boron neutron capture therapy(BNCT)is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10,a stable isotope,is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form,which undergoes instantaneous nuclear fission to produce high-energy,tumoricidal alpha *** primary purpose of this review is to provide an update on the first drug used clinically,sodium borocaptate(BSH),by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug,boronophenylalanine(BPA),which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous ***,BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers,specifically brain tumors and recurrent tumors of the head and neck *** focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with highgrade ***,wewill summarize the studies thatwere carried out in Japan with BSH and subsequently at our own institution,The Ohio State University,and those of several other ***,we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for ***,although there have been intense efforts to develop new and better boron delivery agents for BNCT,none of these have yet been evaluated *** present reportwill provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

关键词： Boron neutron capture therapy(BNCT) boronophenylalanine(BPA) brain tumors head and neck cancer sodium borocaptate(BSH)

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A realistic appraisal of boron neutron capture therapy as a cancer treatment modality

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Cancer Communications 2018年第1期38卷 386-392页

作者： rolf f.barth Zizhu Zhang Tong Liu Department of Pathology The Ohio State UniversityColumbusOH 43210USA. Beijing Capture Technology Company Ltd.Beijing 102445P.R.China

Boron neutron capture therapy(BNCT)is a binary therapeutic modality based on the nuclear capture and fission reac-tions that occur when the stable isotope boron-10 is irradiated with neutrons to produce high-energy alpha particles and recoiling lithium-7 *** this Commentary we will focus on a number of papers that were presented at a Sym-posium entitled“Current Clinical Status of Boron Neutron Capture Therapy and Paths to the future”,which was held in September 2017 at the China National Convention Center in *** were presented by clinicians from Japan,finland,the United States,the China mainland and Taiwan,China who have been working in the multiple disciplines that are required for carrying out clinical *** main focus was on the treatment of patients with malignant brain tumors,recurrent tumors of the head and neck region,and cutaneous *** results obtained in treating these patients were reported in detail and,although most of the patients with brain tumors and head and neck cancer were not cured,there was evidence of some clinical *** there are a number of problems that must be addressed,further clinical studies to evaluate the efficacy of BNCT are ***,despite considerable effort by numerous investigators over the past 40 years,there still are only two boron-containing drugs in clinical use,l-boronophenylalanine(BPA)and sodium borocaptate(BSH).Therefore,until new and more effective boron delivery agents are developed,efforts should be directed to improving the dosing and delivery of BPA and ***,due to a variety of reasons,nuclear reactor-based BNCT has ended except for its use in the China mainland and ***,the future of BNCT depends upon the results of the ongoing Phase II clinical trials that are being carried out in Japan and the soon to be initiated trials that will be carried out in *** the results obtained from these clinical trials are sufficiently promising,then BNCT will

关键词： Boron neutron capture therapy Brain tumors Head and neck cancer Melanomas

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What did Sun Yat-sen really die of?A re-assessment of his illness and the cause of his death

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Chinese Journal of Cancer 2016年第9期35卷 485-489页

作者： rolf f.barth Jie Chen Department of Pathology The Ohio State UniversityColumbusOH 43210USA. Department of Pathology Peking Union Medical College HospitalBeijing 100730P.R.China.

This year is the 150 th anniversary of the birth of Sun Yat-sen(November 12, 1866) and the 91 st year following his death(March 12, 1925). It generally has been believed that the cause of his death was "liver cancer." However, as indicated in the oicial autopsy report, dated March 13, 1925, of the Peking Union Medical College Hospital(PUMCH) in Beijing, the cause of his death in reality was an adenocarcinoma of the gallbladder with direct extension to the liver and diaphragm as well as widespread metastases to the peritoneal cavity. This important piece of information seems to have never been reported in the English language literature, and it was only in 2013 that the true cause of his death was stated in a one-line sentence in a non-medical Chinese online source. It had been mistakenly believed that the cause of Dr. Sun's death was liver cancer, based on the observations made following an exploratory laparotomy, which had been performed at PUMCH on January 26, 1925. The purpose of this short report is to provide more details relating to his terminal illness and to correct the historical record for a medical audience as to the cause of the death of Sun Yat-sen, a very important igure in the history of 20 th century China.

关键词： Sun 死因病情评估中国历史历史记录 sen 肺腺癌

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Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget’s disease with curative responses

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Cancer Communications 2018年第1期38卷 400-409页

作者： Junichi Hiratsuka Nobuhiko Kamitani Ryo Tanaka Eisaku Yoden Ryuji Tokiya Minoru Suzuki rolf f.barth Koji Ono Department of Radiation Oncology Kawasaki Medical School577MatsushimaKurashikiOkayama 701-0192Japan Department of Dermatology Kawasaki Medical SchoolKurashikiOkayama 701-0192Japan Particle Radiation Oncology Kyoto University Research Reactor InstituteOsaka 590-0494Japan Department of Pathology The Ohio State UniversityColumbusOH 43210USA

Background:Although the most commonly recommended treatment for melanoma and extramammary Paget’s disease(EMPD)of the genital region is wide surgical excision of the lesion,the procedure is highly invasive and can lead to functional and sexual *** treatments have been used for local control when wide local exci-sion was not ***,we describe four patients with genital malignancies who were treated with boron neutron capture therapy(BNCT).Methods:The four patients included one patient with vulvar melanoma(VM)and three with genital *** underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery *** were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal ***:All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 *** most severe normal tissue response was moderate skin erosion during the first 2 months,which diminished gradually *** or contact pain persisted for 2 months and resolved com-pletely by 4 ***:Treating VM and EMPD with BNCT resulted in complete local tumor *** on our clinical expe-rience,we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region.

关键词： Boron neutron capture therapy Vulvar melanoma Extramammary Paget’s disease Penis Vulva

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Boron neutron capture therapy of cancer:where do we stand now?

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Cancer Communications 2024年第8期44卷 889-892页

作者： rolf f.barth Gong Wu Maria da Graca H.Vicente John C Grecula Nilendu Gupta Department of Pathology The Ohio State UniversityColumbusOhioUSA Mass Spectrometry and Proteomics facility The Ohio State UniversityColumbusOhioUSA Department of Chemistry Louisiana State UniversityBaton RougeLouisianaUSA Department of Radiation Oncology The Ohio State UniversityColumbusOhioUSA

1 INTRODUCTION,This is the third Editorial/Commentary that one of us(***)has written relating to boron neutron capture therapy(BNCT)[1,2].for those readers who are unfamiliar with BNCT we would refer them to several recent comprehensive reviews[3–5].The second Editorial ended on a hopeful note that with the introduction of acceleratorbased neutron sources(ABNSs),BNCT would enter into the mainstream of radiation therapy[2].

关键词： boron neutron

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Convection Enhanced Delivery of Bioconjugates and Drugs in the Treatment of Brain Tumors

Convection Enhanced Delivery of Bioconjugates and Drugs in t...

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中国抗癌协会神经肿瘤专业委员会第八届学术会议

作者： Weilian Yang rolf f.barth Department of Pathology The Ohio State University

＜正＞Convection enhanced delivery（CED） is a novel approach to directly administer therapeutic agents to the brain,and more specifically to brain *** is based on the administration under positive pressure of a flu...

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硼中子俘获治疗作为癌症治疗方式的现实评估

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癌症 2018年第7期37卷 281-288页

作者： rolf f.barth Zizhu Zhang Tong Liu Department of Pathology The Ohio State UniversityOH 43210USA 北京凯佰特科技股份有限公司北京102445

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于核俘获和裂变反应的二元治疗方式,裂变反应发生于稳定的同位素硼-10被中子辐射时产生高能α粒子和反冲锂-7核。本评论聚焦了2017年9月在北京国家会议中心举办的名为"硼中... 详细信息

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于核俘获和裂变反应的二元治疗方式,裂变反应发生于稳定的同位素硼-10被中子辐射时产生高能α粒子和反冲锂-7核。本评论聚焦了2017年9月在北京国家会议中心举办的名为"硼中子俘获治疗癌症回顾与展望研讨会"上报告的一些文章。来自日本、芬兰、美国、中国大陆和中国台湾地区的临床医生报告了他们的研究结果,他们一直从事BNCT临床应用所需的多学科工作。主要的研究焦点为恶性脑肿瘤、复发性头颈部肿瘤和皮肤黑色素瘤患者的治疗。他们对这些患者的治疗结果进行了详细报道,虽然多数脑肿瘤和头颈癌的患者未被治愈,但获得的证据支持了该疗法具有一定的临床疗效。虽然仍有很多问题须被解决,但评价BNCT疗效的进一步临床研究是可以开展的。首先,尽管过去40年大量研究人员进行了相当大的努力,但临床使用的含硼药物仍只有两种:二羟基苯丙氨酸硼(l-boronophenylalanine,BPA)和巯基硼烷(sodium borocaptate,BSH)。因此,在新的更有效的硼携带剂研发出来之前,改善BPA和BSH的剂量和给药应是努力的方向。第二,由于多种原因,基于核反应堆的BNCT已经在除中国大陆和台湾地区之外的地区停止使用。因此,BNCT的未来取决于日本正在进行的II期临床试验以及芬兰即将启动的试验结果。如果这些临床试验的结果有足够前景,那么BNCT将有一条通往未来的清晰路径,特别是对治疗上具有挑战的恶性肿瘤患者,这些恶性肿瘤类型过去应用反应堆基BNCT进行过治疗。

关键词：硼中子俘获治疗脑肿瘤头颈部肿瘤黑色素瘤

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用于中子俘获治疗的硼携带剂

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癌症 2018年第7期37卷 289-307页

作者： rolf f.barth Peng Mi Weilian Yang Department of Pathology The Ohio State University Department of Radiology Center for Medical Imaging State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center for Biotherapy Neurosurgery and Brain and Nerve Research Laboratory The First Affiliated Hospital of Suzhou University

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于稳定同位素硼-10被中子照射产生高能α粒子时发生的核俘获和裂变反应的二元放射疗法。本综述关注了这个二元系统的一个重要组分,即具有肿瘤靶向性的硼携带剂。目前临床上... 详细信息

硼中子俘获治疗(boron neutron capture therapy,BNCT)是一种基于稳定同位素硼-10被中子照射产生高能α粒子时发生的核俘获和裂变反应的二元放射疗法。本综述关注了这个二元系统的一个重要组分,即具有肿瘤靶向性的硼携带剂。目前临床上正在使用的两种低分子量含硼药物是硼苯丙氨酸(boronophenylalanine,BPA)和硼卡钠(sodium borocaptate,BSH)。尽管还远未达到理想水平,但它们的治疗效果已经在高级别神经胶质瘤、头颈部复发性肿瘤以及小部分皮肤和皮肤外黑色素瘤患者中得到了证实。由于它们存在局限性,在过去的40年中,研究者们一直在为临床应用努力研发具有更高生物分布和摄取性的新型硼携带剂。这些物质包括含硼的卟啉、氨基酸、多胺、核苷、多肽、单克隆抗体、脂质体和各种类型的纳米颗粒,以及硼簇合物和共聚物。然而到目前为止,还没有一种化合物获得过有说服力的数据,能使之进入临床生物分布研究。因此,目前进一步提高BNCT临床疗效的最佳途径是优化BPA和BSH单独使用或联合使用的给药模式和递送方式,并希望未来的研究能发现更新更好的硼携带剂供临床使用。

关键词：硼携带剂中子俘获治疗脑瘤头颈部肿瘤黑色素瘤

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卡波西肉瘤广泛肺间质弥漫浸润一例

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中华病理学杂志 2002年第6期31卷 563-564页

作者：谭光明 rolf f.barth Cynthia M.Magro Gerard J Nuovo DepartmentofPathology OhioStateUniversityMedicalCenter

患者男，46岁。15年前发现HIV阳性。1年前左颊部出现红色斑疹，活检示卡波西肉瘤。偶有室上性心动过速，因咳嗽、气促、痰中带血一周而于2002年1月16日就诊。无发热、寒颤及恶心、呕吐等症状。X光片示右侧胸腔积液及下肺叶实变（图1）... 详细信息

患者男，46岁。15年前发现HIV阳性。1年前左颊部出现红色斑疹，活检示卡波西肉瘤。偶有室上性心动过速，因咳嗽、气促、痰中带血一周而于2002年1月16日就诊。无发热、寒颤及恶心、呕吐等症状。X光片示右侧胸腔积液及下肺叶实变（图1）。体检：一般情况尚可，体温37℃，血压131/83 mm Hg，脉搏85次／min，呼吸24次／min。双侧瞳孔等大等圆，对光反射好。口腔黏膜有少量干血迹。心律齐，无杂音。右肺呼吸音减弱，可闻及干性及湿性啰音。腹平软，肠鸣音正常。四肢无异常。一周后患者因病情恶化，出现呼吸循环衰竭，治疗无效而死亡。

关键词：卡波西肉瘤肺间质弥漫浸润肺肿瘤诊断 X线诊断治疗病例报告

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