|Table of Contents|

Research progress and clinical application of boron carrier in BNCT therapy

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 09
Page:
1744-1751
Research Field:
Publishing date:

Info

Title:
Research progress and clinical application of boron carrier in BNCT therapy
Author(s):
SU Wei1; 2; 3; 4; 5; 6; LEI Huiwen1; 2; 3; 4; 5; 6; DOU Zhihui1; 2; 3; 4; 5; 6; ZHANG Hong1; 2; 3; 4; 5; DI Cuixia1; 2; 3; 4; 5
Keywords:
boron neutron capture therapy; binary radiotherapy; boron carrier; boron dose measurement system
PACS:
R730.5
DOI:
10.3969/j.issn.1672-4992.2023.09.031
Abstract:
Boron neutron capture therapy(BNCT) is a binary radiotherapy，and it is one of the tumor treatment methods with broad development prospects at present.When isotope 10B is irradiated by neutrons，it undergoes nuclear capture and fission reaction to produce high-energy alpha particles，which are used to kill cancer cells.Since BNCT was first put forward in 1930s and then used in tumor treatment，boron neutron capture therapy has gradually developed all over the world.BNCT has achieved remarkable results in glioma，melanoma，head and neck tumors and other diseases.At the same time，the main problems faced by BNCT are to open up more efficient boron carrier，establish more accurate boron dose measurement system and develop electron linear accelerator neutron source.In this paper，mainly introduced the principle and therapeutic advantages of boron neutron capture therapy，and as the core component of BNCT，which the development history and clinical application of boron carrier，as well as the current situation of accurate measurement of boron dose.It is helpful to reveal the potential of BNCT in tumor treatment.

References:

［1］王淼，童永彭.硼中子俘获治疗的进展及前景［J］.同位素，2020，33(1):13.WANG M，TONG YP.Progress and prospect of boron neutron capture therapy［J］.Isotope，2020，33(1):13.
［2］江海燕，吴宜灿，罗乐.α粒子对人体癌细胞损伤过程的蒙特卡罗模拟及分析［J］.物理，2004，33(9):5.JIANG HY，WU YC，LUO L.Monte Carlo simulation and analysis of the damage process of human cancer cells caused by α particle［J］.Physics，2004，33(9):5.
［3］罗军益，何佳恒.硼中子俘获疗法治疗肿瘤及相关技术研究进展［J］.辐射防护通讯，2010，30(2):4.LUO JY，HE JH.Research progress of boron neutron captures therapy for tumor and related technologies［J］.Radiation Protection Communication，2010，30(2):4.
［4］ROLF F BARTH，MI P，YANG WL.Boron delivery agents for neutron capture therapy of cancer［J］.Cancer Communications，2018，38(1):371-385.
［5］周永茂.硼中子俘获疗法中的硼浓度探测［J］.现代科学仪器，2010，10(4):7-12.ZHOU YM.Detection of boron concentration in boron neutron capture therapy［J］.Modern Scientific Instruments，2010，10(4):7-12.
［6］KRUGER PG.Some biological effects of nuclear disintegration products on neoplastic tissue［J］.Pros Nat Accad Sic USA，1940，26(3)：181-192.
［7］NEDUNCHEZHIAN K，ASWATH N，THIRUPPATHY M，et al.Boron neutron capture therapy-A literature review［J］.Journal of Clinical & Diagnostic Research，2016，10(12):ZE01.
［8］HIDEGHETY K，SAUERWEIN W，WITTIG A，et al.Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial［J］.Journal of Neuro-Oncology，2003，62(1):145-156.
［9］MISHIMA Y,ICHIHASHI M,HATTA S,et al.First human clinical trial of melanoma neutron capture.Diagnosis and therapy［J］.Strahlentherapie und Onkologie,1989,165(2-3):251-254.
［10］SNYDER HR，REEDY AJ，LENNARZ WJ.Synthesis of aromatic boronic acids.Aldehydo boronic acids and a boronic acid analog of tyrosine1［J］.Journal of the American Chemical Society，1958，80(4):835.
［11］UMANO M，UECHI K，URIUDA T，et al.Tumor accumulation of ε-poly-lysines-based polyamines conjugated with boron clusters［J］.Applied Radiation and Isotopes，2011，69(12):1765-1767.
［12］MIYATAKE SI，KAWABATA S，HIRAMATSU R，et al.Boron neutron capture therapy for malignant brain tumors［J］.Neurologia Medico-Chirurgica，2016，56(7):361.
［13］BARTH RF，VICENTE M，HARLING OK，et al.Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer［J］.Radiation Oncology，2012，7(1):146.
［14］DETTA A，CRUICKSHANK GS.L-amino acid transporter-1 and boronophenylalanine-based boron neutron capture therapy of human brain tumors［J］.Cancer Research，2009，69(5):2126-2132.
［15］KABALKA GW，SHAIKH AL，BARTH RF，et al.Boronated unnatural cyclic amino acids as potential delivery agents for neutron capture therapy［J］.Applied Radiation and Isotopes，2011，69(12):1778-1781.
［16］SVANTESSON E，CAPALA J，MARKIDES KE，et al.Determination of boron-containing compounds in urine and blood plasma from boron neutron capture therapy patients［J］.The Importance of Using Coupled Techniques，2002，74(20)：5358-5363.
［17］LI J,SHI Y,ZHANG Z，et al.A metabolically stable boron-derived tyrosine serves as a theranostic agent for positron emission tomography guided boron neutron capture therapy［J］.Bioconjugate Chemistry，2019，30(11):2870-2878.
［18］LI Z，KONG Z，CHEN J，et al.F-Boramino acid PET/CT in healthy volunteers and glioma patients［J］.European Journal of Nuclear Medicine and Molecular Imaging，2021，48(10):3113-3121.
［19］WEINER GEORGE J.Building better monoclonal antibody-based therapeutics［J］.Nature Reviews Cancer，2015，15(6):361-370.
［20］PJ CARTER，PD SENTER.Antibody-drug conjugates in cancer therapy［J］.The Cancer Journal，2012，14(3):154-169.
［21］PORRAS I，PRAENA J，ARIAS DE SAAVEDRA F，et al.BNCT research activities at the Granada group and the project NeMeSis：Neutrons for medicine and sciences，towards an accelerator-based facility for new BNCT therapies，medical isotope production and other scientific neutron applications［J］.Appl Radiat Isot，2020，165:109247.
［22］邓云秋.EGFR单克隆抗体靶向药物治疗脑胶质瘤的研究进展［J］.中国处方药，2018，16(8):2.DENG YQ.Research progress of EGFR monoclonal antibody targeting drugs in the treatment of glioma［J］.Chinese Prescription Drugs，2018，16(8):2.
［23］WONG SF.Cetuximab：An epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer［J］.Clinical Therapeutics，2005，27(6):684-694.
［24］HAFEEZ U，PARAKH S，GAN HK，et al.Antibody-drug conjugates for cancer therapy［J］.Molecules，2020，25(20):4764.
［25］高峰，苑娇梅.硼中子俘获治疗药物的研究进展［J］.中国新药杂志，2010，19(4)：296-300.GAO F，YUAN JM.Research progress of boron neutron capture therapy drugs［J］.Chinese Journal of New Drugs，2010，19(4):296-300.
［26］MADERNA A，HUERTAS R，HAWTHORNE MF，et al.Synthesis of a porphyrin-labelled carboranyl phosphate diester：a potential new drug for boron neutron capture therapy of cancer［J］.Chemical Communications，2002,10(16):1784-1785.
［27］LAUCERI R，PURRELLO R，SHETTY SJ，et al.Interactions of anionic carboranylated porphyrins with DNA［J］.Journal of the American Chemical Society，2001，123(24):5835-5846.
［28］BHUPATHIRAJU N，HU X，ZHOU Z，et al.Synthesis and in vitro evaluation of BBB permeability，tumor cell uptake，and cytotoxicity of a series of carboranylporphyrin conjugates［J］.Journal of Medicinal Chemistry，2014，57(15):6718.
［29］ISSA F，KASSIOU M，RENDINA LM.Boron in drug discovery：carboranes as unique pharmacophores in biologically active compounds［J］.Chemical Reviews，2011，111(9):5701-5722.
［30］AFSHARZADEH M，HASHEMI M，BABAEI M，et al.PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells［J］.Journal of Cellular Physiology，2019，235(5)：4618-4630.
［31］XIAO RZ,ZENG ZW,ZHOU GL,et al.Recent advances in PEG-PLA block copolymer nanoparticles［J］.Int J Nanomedicine,2010,15(5):1057-1065.
［32］RENNER M，MIURA M，EASSON M，et al.Recent progress in the syntheses and biological evaluation of boronated porphyrins for boron neutron-capture therapy［J］.Current Medicinal Chemistry，2006，6(2):145-157.
［33］GLASKOVA-KUZMINA T,STARKOVA O,GAIDUKOVS S,et al.Durability of biodegradable polymer nanocomposites［J］.Polymers(Basel),2021,13(19):3375.
［34］HATTORI Y，KUSAKA S，MUKUMOTO M，et al.Biological evaluation of dodecaborate-containing L-amino acids for boron neutron capture therapy［J］.Journal of Medicinal Chemistry，2012，55(15):6980.
［35］KHALIL A，ISHITA K，ALI T，et al.N3-substituted thymidine bioconjugates for cancer therapy and imaging［J］.Future Medicinal Chemistry，2013，5(6):677-692.
［36］KAWABATA S，YANG W，BARTH RF，et al.Convection enhanced delivery of carboranylporphyrins for neutron capture therapy of brain tumors［J］.Journal of Neuro-Ocology，2011，103(2):175.
［37］AHRENS VM，RENE FRANK，STADLBAUER S，et al.Incorporation of ortho-carbaboranyl-Nε-modified L-lysine into neuropeptide Y receptor Y1-and Y2-selective analogues［J］.Journal of Medicinal Chemistry，2011，54(7):2368-2377.
［38］WU G，BARTH RF，YANG W，et al.Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab(IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy［J］.Bioconjugate Chemistry，2004，15(1):185-194.
［39］HEBER EM，HAWTHORNE MF，KUEFFER PJ，et al.Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model［J］.Proceedings of the National Academy of Sciences，2014，111(45):16077-16081.
［40］MAITZ CA，KHAN AA，KUEFFER PJ，et al.Validation and comparison of the therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes in multiple murine tumor models-sciencedirect［J］.Translational Oncology，2017，10(4):686-692.
［41］KUTHALA N，VANKAYALA R，LI YN，et al.Engineering novel targeted boron-10-enriched theranostic nanomedicine to combat against murine brain tumors via MR imaging-guided boron neutron capture therapy［J］.Advanced Materials，2017，29(31):1700850.
［42］H NAKAMURA，H KOGANEI，T MIYOSHI，et al.Antitumor effect of boron nitride nanotubes in combination with thermal neutron irradiation on BNCT［J］.Bioorganic & Medicinal Chemistry Letters，2015，25(2):172-174.
［43］TAMANOI F,CHINNATHAMBI S,LAIRD M，et al.Construction of boronophenylalanine loaded biodegradable periodic mesoporous organosilica nanoparticles for bnct cancer therapy［J］.International Journal of Molecular Sciences，2021，22(5):2251.
［44］SARA KHADEMI，SAEED SARKAR，ALI SHAKERI -ZADEH，et al.Corrigendum to "Targeted gold nanoparticles enable molecular CT imaging of head and neck cancer：An in vivo study"-Science direct［J］.The International Journal of Biochemistry & Cell Biology，2019，114(2):120.
［45］JIANG Q，WANG K，ZHANG X，et al.Platelet membrane-camouflaged magnetic nanoparticles for ferroptosis-enhanced cancer immunotherapy［J］.Small，2020，16(22):1-17.
［46］CA CHILLI，GRANDI S，CIANA A，et al.Biocompatibility of functionalized boron phosphate(BPO4) nanoparticles for boron neutron capture therapy(BNCT) application［J］.Nanomedicine Nanotechnology Biology & Medicine，2014，10(3):589-597.
［47］MIYATAKE S，KAWABATA S，KAFIMOTO Y，et al.Modified boron neutron capture therapy for malignant gliomas performed using epithermal neutron and two boron compounds with different accumulation mechanisms：an efficacy study based on findings on neuroimages［J］.Chinese Journal of Neurooncology，2005，103(4):266-276.
［48］LOCHER GL.Biological effects and therapeutic possibilities of neutrons［J］.Am J Roentgenol Radium Ther,1936,1453(4):36.
［49］王鹏，章翔，江新标，等.硼中子俘获疗法治疗小鼠颅内G422胶质细胞瘤［J］.中华神经医学杂志，2007，6(9):892-895.WANG P，ZHANG X，JIANG XB，et al.Treatment of intracranial G422 glioma in mice with boron neutron capture therapy［J］.Chinese Journal of Neuromedicine，2007，6(9):892-895.
［50］徐菁，王俊杰，魏启春.硼中子俘获治疗临床应用进展及展望［J］.科学通报，2022，67(14):1479-1489.XU J，WANG JJ，WEI QC.Boron neutron capture therapy in clinical application:Progress and prospect［J］.Chinese Science Bulletin，2022，67(14):1479-1489.
［51］KAWABATA S,SUZUKI M,HIROSE K,et al.Accelerator-based BNCT for patients with recurrent glioblastoma:a multicenter phase Ⅱ study［J］.Neuro-Oncology Advances,2021,3(1):67.
［52］何静，汤晓斌，刘渊豪，等.硼中子俘获治疗头颈部肿瘤临床试验进展［J］.中华放射医学与防护杂志，2020，40(8):6.HE J，TANG XB，LIU YH，et al.Progress in clinical trials of boron neutron capture therapy for head and neck tumors［J］.Chinese Journal of Radiation Medicine and Protection，2020，40(8):6.
［53］周永茂.迈入新世纪的硼中子俘获疗法（BNCT）［J］.中国工程科学，2012，14(8):10.ZHOU YM.Boron neutron capture therapy(BNCT) in the new century［J］.China Engineering Science，2012，14(8):10.
［54］HIROSE K,KONNO A,HIRATSUKA J,et al.Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan(10 B) for recurrent or locally advanced head and neck cancer(JHN002)：An open-label phase Ⅱ trial［J］.Radiotherapy and Oncology，2021，155:182-187.
［55］HATANAKA H.Clinical results of boron neutron capture therapy［J］.Basic Life,1990,69:15-21.
［56］LIM D,QUAH DS,LEECH M,et al.Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer［J］.Applied Radiation and Isotopes，2015，160:237-241.
［57］母义明.垂体瘤诊治进展［J］.解放军医学杂志，2017，42(7):576-582.MU YM.Progress in diagnosis and treatment of pituitary tumor［J］.Journal of PLA Medicine，2017，42(7):576-582.
［58］王志成，代从新，卢琳，等.硼中子俘获疗法治疗中枢神经系统肿瘤的研究进展［J］.中国微侵袭神经外科杂志，2018，23(11):4.WANG ZC，DAI CX，LU L，et al.Research progress of boron neutron capture therapy for central nervous system tumors［J］.Chinese Journal of Minimally Invasive Neurosurgery，2018，23(11):4.
［59］刘小海.叶酸受体靶向无功能垂体腺瘤的诊治及其机制研究［D］.北京：北京协和医学院 中国医学科学院 北京协和医学院 清华大学医学部 中国医学科学院，2012.LIU XH.Diagnosis，treatment and mechanism of folate receptor targeting nonfunctional pituitary adenoma［D］.Beijing:Peking Union Medical College，Chinese Academy of Medical Sciences，Tsinghua University Medical College，2012.
［60］DAI CX,CAI F,CHU HK,et al.Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas［J］.Science China,2013(2):163-173.
［61］MISHIMA Y,HONDA C,ICHIHASHI M,et al.Treatment of malignant melanoma by single thermal neutron capture therapy with melanoma-seeking 10B-compound［J］.Lancet,1989,2(8659):388-389.
［62］PR MENENDEZ,ROTH B,PEREIRA MD,et al.BNCT for skin melanoma in extremities:Updated argentine clinical results［J］.Appl Radiat Isot,2009,67(7-8):S50-S53.
［63］JUNICHI H，NOBUHIKO K，RYO T，et al.Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget’s disease with curative responses［J］.Cancer Communications，2018，38(1):38.
［64］HATANAKA H，NAKAGAWA Y.Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy［J］.Int J Radiat Oncol Biol Phys，1994，28(5):1061-1066.
［65］李凤林，罗志富，邓欣荣，等.分光光度法测量生物组织中BPA含量［J］.同位素，2013，26(3):163-169.LI FL，LUO ZF，DENG XR，et al.Spectrophotometric measurement of BPA content in biological tissues［J］.Journal of Isotopes，2013，26(3):163-169.
［66］唐秀欢，江新标，王鹏，等.亚细胞微观硼浓度测量方法研究［J］.原子能科学技术，2008，42(6):5.TANG XH，JIANG XB，WANG P，et al.Study on measurement method of subcellular microscopic boron concentration［J］.Atomic Energy Science and Technology，2008，42(6):5.
［67］LAGE S，RAIMUNDO J，BROTAS V，et al.Detection and sub-cellular distribution of the amnesic shellfish toxin，domoic acid，in the digestive gland of Octopus vulgaris during periods of toxin absence［J］.Marine Biology Research，2012，8(8):784-789.
［68］彭旦，鲁谨，邹淑芸，等.医院中子照射器中子束流出口处热中子注量率的测量［J］.原子能科学技术，2013，47(8):3.PENG D，LU J，ZOU SY，et al.Measurement of thermal neutron fluence rate at neutron beam exit of hospital neutron irradiator［J］.Atomic Energy Science and Technology，2013，47(8):3.
［69］王静娟.一体化PET/MR在脑功能方面的研究进展［J］.医学影像学杂志，2017，27(9):3.WANG JJ.Research progress of integrated PET/MR in brain function［J］.Journal of Medical Imaging，2017，27(9):3.

Memo

Memo:
National Natural Science Foundation of China（No.U1632270）;National Natural Science Foundation of China（No.11675234）;国家自然科学基金联合重点项目（编号：U1632270）；国家自然科学基金面上项目（编号：11675234）；科技部国家重点研发计划（编号：2018YFE0205100，2018YFE0205103）
Last Update: 2023-03-30