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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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neutron capture therapy (NCT) & In-Hospital neutron Irradiator (IHNI)——a new technology on binary targeting radiation therapy of cancer

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Engineering Sciences 2009年第4期7卷 2-21页

作者： Zhou Yongmao China Zhongyuan Engineering Corporation of China National Nuclear Corporation Beijing 100191 China

BNCT is finally becoming ＂a new option against cancer＂. The difficulties for its development progress of that firstly is to improve the performance of boron compounds, secondly, it is the requirements of quantification and accuracy upon radiation dosimetry evaluation in clinical trials. Furthermore, that is long anticipation on hospital base neutron sources. It includes dedicated new NCT reactor, accelerator based neutron sources, and isotope source facilities. In ad- dition to reactors, so far, the technology of other types of sources for clinical trials is not yet completely proven. The In- Hospital neutron lrradiator specially designed for NCT, based on the MNSR successfully developed by China, can be installed inside or near the hospital and operated directly by doctors. The Irradiator has two neutron beams for respective treatment of the shallow and deep tumors. It is expected to initiate operation in the end of this year. It would provide a safe, low cost, and effective treatment tool for the NCT routine application in near future.

关键词： neutron capture therapy boron compound radiation dosimetry neutron beam in-hospital neutron irradi- ator

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About Radiation in ^natGd for neutron capture therapy

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Journal of Health Science 2016年第1期4卷 35-44页

作者： Gayratulla A. Kulabdullaev G. A. Abdullaeva A. A. Kim T. T. Rakhmonov A. Kurmantaev Institute of Nuclear Physics Uz AS Tashkent Uzbekistan University of Akhmet Yasawi Turkestan Kazakhstan

In the present work, based on publications dedicated to ^natGd natural gadolinium isotopes, characteristics of secondary particles are analysed in details for various neutron-induced reactions. Characteristics of the secondary particles produced in these reactions that make significant contribution to absorbed dose are estimated. It is also established that the main contribution to the absorbed dose is made by secondary particles produced in interactions of neutrons and ^155Gd and ^157Gd isotopes. From comparison of gamma-radiation spectra it is defined that the amount of γ-quanta with energies 0-400 keV （i.e. effective γ-quanta） produced in the （n,γ）-reaction by ^155Gd is higher than that by ^157Gd. Compared spectra of other particles （internal conversion electrons, Auger electrons, x-ray radiation） have shown that earlier used average values of their energy must be defined more precisely. When biological objects are irradiated for approximately 30 minutes by epithermal neutrons in the ^natGd NCT （Gadolinium-based neutron-capture therapy）, one should take into account energies of secondary particles produced by ^152Gd, ^154Gd, ^156Gd, ^158Gd and ^160Gd isotopes as they have high linear energy transfer （LET）. It is demonstrated that when combined, all these secondary particles can make significant contribution to the absorbed dose at neutron-irradiation of biological objects by the ^natGd NCT technique.

关键词： Nuclear reactions natural gadolinium isotopes secondary particles conversion electrons epithermal neutrons neutron capture therapy radiation biological effect.

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Gadolinium neutron capture Reaction-Induced Nucleodynamic therapy Potentiates Antitumor Immunity

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CCS Chemistry 2023年第11期5卷 2589-2602页

作者： Dongban Duan Yi Han Zhiyu Tu Haoxuan Guo Zizhu Zhang Yaxin Shi Jiyuan Li Qi Sun Junyi Chen Zhu Li Tong Liu Daqing Cui Zhibo Liu Beijing National Laboratory for Molecular Sciences Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental ScienceNMPA Key Laboratory for Research and Evaluation of RadiopharmaceuticalsKey Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871 Department of Radiochemistry China Institute of Atomic EnergyBeijing 102413 Department of Nuclear Science and Technology School of Energy and Power EngineeringXi’an Jiaotong UniversityXi’an 710049 Beijing Nuclear Industry Hospital Beijing 100045 Peking University–Tsinghua University Center for Life Sciences Peking UniversityBeijing 100871 Key Laboratory of Carcinogenesis and Translational Research Department of Nuclear MedicinePeking University Cancer Hospital&InstituteBeijing Beijing capture Tech Co.Ltd. Beijing 102413 Department of Materials and Environmental Chemistry Stockholm UniversityStockholm SE-10691 Changping Laboratory Beijing 102206

A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal *** neutron capture therapy(GdNCT)is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations(e.g.,Auger electrons,γ-rays,etc.)in cancer cells when^(157Gd)is irradiated with thermal ***,its clinical application has been postponed due to the poor ability of Auger electrons andγ-rays to kill ***,we engineered a^(157Gd)-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both•OH and immunogenic 1O2 in cancer cells,thereby provoking a strong antitumor immune *** study unveils the fact and mechanism that NDT heats tumor *** unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectlymatches the size of *** tumormodels,NDT causes nearly complete regression of both primary and distant tumor ***,this^(157Gd)-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy;its applicationmay expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases,which are responsible for 90%of all cancer deaths.

关键词： neutron capture therapy radiochemistry radiotherapy immunotherapy

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