Speed up the source
Physicists plan to complete the modernization of the accelerator neutron source for boron-neutron capture therapy in 2022.
The next stage of modernization of the accelerator neutron source for boron-neutron capture therapy (BNRT) has been completed at the G.I. Budker Institute of Nuclear Physics SB RAS (INP SB RAS). As a result of the work carried out, the proton beam current was increased from 5 to 8.5 mA (milliamps) – in the future, this will reduce the irradiation time of patients by almost half. By 2022, INP SB RAS specialists plan to prepare an accelerator neutron source for preclinical testing. By the same time, biologists of the Institute of Chemical Biology and Fundamental Medicine SB RAS (IHBFM SB RAS) expect to complete one of the stages of creating a domestic drug for targeted delivery of boron, necessary for the treatment of oncological diseases by the BNZT method. The work of Novosibirsk physicists is supported by a grant from the Russian Academy of Sciences and at the moment is only of a research nature.
Boron neutron capture therapy (BNRT) is a method of selective destruction of malignant tumor cells. Boron-containing solution is injected into human blood, after which boron accumulates in cancer cells. Then the tumor is irradiated with a stream of epithelial neutrons, boron nuclei absorb neutrons, nuclear reactions with high energy release occur, as a result, diseased cells die. The technique has been tested on nuclear reactors that have been used as a neutron source, but the introduction of BNZT into clinical practice on them is difficult. Charged particle accelerators are more suitable for these purposes because they are compact, safe and provide the best quality of the neutron beam.
The idea of an epithermal neutron source based on a new type of charged particle accelerator – a tandem accelerator with vacuum insulation and a lithium neutron generating target - was proposed at the INP SB RAS in 1998, after which an installation was created here and the first neutron beam was obtained. The high quality of the beam was confirmed by experiments on cell cultures and laboratory animals.
"The effectiveness of the method in relation to tumor tissues has been shown by experiments on cell cultures and laboratory animals (mice)," said Vladimir Kanygin, head of the Laboratory of Biomedical Problems of boron–neutron capture therapy at NSU, neurosurgeon, oncologist, Candidate of Medical Sciences. – In the near future, the issue of irradiation of mammals closer to humans in physiological parameters, namely cats and dogs, will be resolved. The stage of preclinical work is also planned to be carried out on the basis of the laboratory of biomedical problems of BNZT NSU with the participation of a number of large research organizations in Novosibirsk and Moscow."
Recently, the next stage of modernization of the accelerator neutron source for BNZT was completed at the INP SB RAS, which made it possible to improve the beam parameters. The ultimate goal of such work is to achieve the technical characteristics required for boron–neutron capture therapy in a clinical setting.
"After studying the physical processes and upgrading the accelerator, we doubled the current of the proton beam, reaching the value with which therapy can be carried out in the recommended time of less than one hour," commented Sergey Taskaev, a leading researcher at the INP SB RAS, head of the BNZT laboratory of NSU, Doctor of Physical and Mathematical Sciences.
The project of a tandem accelerator with vacuum insulation and a lithium neutron generating target of the INP SB RAS is aimed at creating a neutron beam of the best quality, minimally damaging healthy tissues. The technical and physical solutions implemented in the Institute's installation make it possible to form a beam with as few fast and slow neutrons as possible, which give rise to harmful radiation. Healthy cells still receive a dose of radiation, but it is not harmful to them. Within the framework of the RNF grant, the specialists of the INP SB RAS plan to bring the remaining physical parameters of the accelerator neutron source to the level necessary for boron-neutron capture therapy.
"We plan that by the end of the fourth year of work within the framework of the RNF grant, the installation will be prepared for certification for preclinical tests," added Sergey Taskaev.
The BNZT methodology has two most difficult scientific and technical tasks that need to be solved. The first is the creation of a reliable compact neutron source with the necessary characteristics. The second is the development of a suitable method for delivering boron–10 atoms to damaged tissue. In Russia, many scientific groups, including specialists of the IHBFM SB RAS, are engaged in solving the latter. They are developing a domestic boron-10-containing drug in three directions, but the ultimate goal is the same – the creation of a drug that will deliver boron to tumor cells with high efficiency.
The BNZT accelerator of the INP SB RAS. Photo by A. Makarov.
"The problem of developing new drugs is quite acute. There are only two drugs for BNZT in the world – borphenylalanine and borcaptate, – said Vladimir Richter, head of the Laboratory of Biotechnologies of the IHBFM SB RAS, Candidate of Biological Sciences. – New drugs should effectively deliver boron to tumor cells and, bypassing healthy tissues, create the maximum concentration of this substance in them. In our Institute, in cooperation with the laboratory of Doctor of Chemical Sciences Vladimir Shelkovnikov (Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov SB RAS), three laboratories work in this direction. Experts are investigating the possibilities of three different candidates for the role of boron carrier – albumin protein molecules, aptamers (short sequences of nucleic acids) and bacteriophages. In the next three years, we hope to create a drug that binds to glioblastoma with much greater efficiency than available foreign analogues."
At the moment, five projects are being implemented in the world to create specialized clinics for the treatment of cancer using BNRT – three in Japan, one in China, which is being done jointly by the INP SB RAS and the American company TAE Life Sciences, and one in Finland. "Within the framework of the development program of the Novosibirsk Scientific Center "Akademgorodok 2.0", the possibility of implementing the project "Boron-neutron capture therapy of oncological diseases, the purpose of which is to introduce into medical practice a unique technology to combat incurable forms of cancer," added Igor Shikhovtsev, senior researcher at the INP SB RAS, Candidate of Physical and Mathematical Sciences. - "The implementation of the project implies the creation of a typical BNZT center, a unique neutron generator for its equipment, a domestic boron-10–containing drug for BNZT and training of personnel in this area - doctors and medical physicists."
The next stage of modernization of the accelerator neutron source for boron-neutron capture therapy (BNRT) has been completed at the G.I. Budker Institute of Nuclear Physics SB RAS (INP SB RAS). As a result of the work carried out, the proton beam current was increased from 5 to 8.5 mA (milliamps) – in the future, this will reduce the irradiation time of patients by almost half. By 2022, the specialists of the INP SB RAS plan to prepare an accelerator neutron source for conducting preclinical tests. By the same time, biologists of the Institute of Chemical Biology and Fundamental Medicine SB RAS (IHBFM SB RAS) expect to complete one of the stages of creating a domestic drug for targeted delivery of boron, necessary for the treatment of oncological diseases by the BNZT method. The work of Novosibirsk physicists is supported by a grant from the Russian Academy of Sciences and at the moment is only of a research nature.
Boron neutron capture therapy (BNRT) is a method of selective destruction of malignant tumor cells. Boron-containing solution is injected into human blood, after which boron accumulates in cancer cells. Then the tumor is irradiated with a stream of epithelial neutrons, boron nuclei absorb neutrons, nuclear reactions with high energy release occur, as a result, diseased cells die. The technique has been tested on nuclear reactors that have been used as a neutron source, but the introduction of BNZT into clinical practice on them is difficult. Charged particle accelerators are more suitable for these purposes because they are compact, safe and provide the best quality of the neutron beam.
The idea of an epithermal neutron source based on a new type of charged particle accelerator – a tandem accelerator with vacuum insulation and a lithium neutron generating target - was proposed at the INP SB RAS in 1998, after which an installation was created here and the first neutron beam was obtained. The high quality of the beam was confirmed by experiments on cell cultures and laboratory animals.
"The effectiveness of the method in relation to tumor tissues has been shown by experiments on cell cultures and laboratory animals (mice)," said Vladimir Kanygin, head of the Laboratory of Biomedical Problems of boron–neutron capture therapy at NSU, neurosurgeon, oncologist, Candidate of Medical Sciences. – In the near future, the issue of irradiation of mammals closer to humans in physiological parameters, namely cats and dogs, will be resolved. The stage of preclinical work is also planned to be carried out on the basis of the laboratory of biomedical problems of BNZT NSU with the participation of a number of large research organizations in Novosibirsk and Moscow."
Recently, the next stage of modernization of the accelerator neutron source for BNZT was completed at the INP SB RAS, which made it possible to improve the beam parameters. The ultimate goal of such work is to achieve the technical characteristics required for boron–neutron capture therapy in a clinical setting.
"After studying the physical processes and upgrading the accelerator, we doubled the current of the proton beam, reaching the value with which therapy can be carried out in the recommended time of less than one hour," commented Sergey Taskaev, a leading researcher at the INP SB RAS, head of the BNZT laboratory of NSU, Doctor of Physical and Mathematical Sciences.
The project of a tandem accelerator with vacuum insulation and a lithium neutron generating target of the INP SB RAS is aimed at creating a neutron beam of the best quality, minimally damaging healthy tissues. The technical and physical solutions implemented in the Institute's installation make it possible to form a beam with as few fast and slow neutrons as possible, which give rise to harmful radiation. Healthy cells still receive a dose of radiation, but it is not harmful to them. Within the framework of the RNF grant, the specialists of the INP SB RAS plan to bring the remaining physical parameters of the accelerator neutron source to the level necessary for boron-neutron capture therapy.
"We plan that by the end of the fourth year of work within the framework of the RNF grant, the installation will be prepared for certification for preclinical tests," added Sergey Taskaev.
The BNZT methodology has two most difficult scientific and technical tasks that need to be solved. The first is the creation of a reliable compact neutron source with the necessary characteristics. The second is the development of a suitable method for delivering boron–10 atoms to damaged tissue. In Russia, many scientific groups, including specialists of the IHBFM SB RAS, are engaged in solving the latter. They are developing a domestic boron-10-containing drug in three directions, but the ultimate goal is the same – the creation of a drug that will deliver boron to tumor cells with high efficiency.
The BNZT accelerator of the INP SB RAS. Photo by A. Makarov.
"The problem of developing new drugs is quite acute. There are only two drugs for BNZT in the world – borphenylalanine and borcaptat, – said Vladimir Richter, head of the Laboratory of Biotechnology of the IHBFM SB RAS, Candidate of Biological Sciences. – New drugs should effectively deliver boron to tumor cells and, bypassing healthy tissues, create the maximum concentration of this substance in them. In our Institute, in cooperation with the laboratory of Doctor of Chemical Sciences Vladimir Shelkovnikov (Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov SB RAS), three laboratories work in this direction. Experts are investigating the possibilities of three different candidates for the role of boron carrier – albumin protein molecules, aptamers (short sequences of nucleic acids) and bacteriophages. In the next three years, we hope to create a drug that binds to glioblastoma with much greater efficiency than available foreign analogues."
At the moment, five projects are being implemented in the world to create specialized clinics for the treatment of cancer using BNRT – three in Japan, one in China, which is being done jointly by the INP SB RAS and the American company TAE Life Sciences, and one in Finland. "Within the framework of the development program of the Novosibirsk Scientific Center "Akademgorodok 2.0", the possibility of implementing the project "Boron-neutron capture therapy of oncological diseases" is being discussed, the purpose of which is to introduce into medical practice a unique technology to combat incurable forms of cancer," added Igor Shikhovtsev, senior researcher at the INP SB RAS, Candidate of Physical and Mathematical Sciences. "The implementation of the project implies the creation of a typical BNZT center, a unique neutron generator for its equipment, a domestic boron–10-containing drug for BNZT and training of personnel in this area - doctors and medical physicists."
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