MOSCOW, August 31, Vladislav Strekopytov. The scientists presented the first domestic installation for boron neutron capture therapy of oncological diseases. Clinical trials will begin next summer. The advantages of the new method, which is also effective against inoperable tumors, can be found in the article .
Right on target
Cancer occurs due to altered cells that divide uncontrollably. If the immune system does not recognize them in time, the tumor grows, secondary foci of pathology are formed in organs and tissues — metastases, bringing death closer
Complete removal of the tumor by surgery is not always possible. In addition, even after a successful, at first glance, operation, relapses are not uncommon, hidden metastases are found. In this case, doctors are forced to resort to radiation and chemotherapy, which also affect healthy cells and tissues.
The task of scientists is to increase the accuracy of exposure, to develop so-called targeted methods. One option is to use the energy of nuclear reactions.
Nuclear explosion inside a cell
In 1932, British physicist James Chadwick discovered the neutron. It soon became clear that boron-10 nuclei have an amazing ability to capture slow (thermal) neutrons, resulting in decay into lithium-7 and helium-4 nuclei (alpha particles). Boron-neutron capture (as it was called) is accompanied by the release of energy, but all of it is dissipated within a radius of five to seven microns (micrometers). This is the range of newly formed particles.
In 1936, the American radiologist Gordon Locher, and in the 1940s, independently of him, the Soviet physician and chemist Anatoly Kachurin, proposed the use of this nuclear microexplosion to treat cancer. The cell size is about ten microns, and if you deliver boron radioisotopes directly to the tumor, irradiate them with neutrons, then the surrounding healthy tissues will not be affected by the microexplosion. jpg» media-type=»photo» data-crop-ratio=»0.737347294938918″ data-crop-width=»600″ data-crop-height=»442″ data-source-sid=»» class=»lazyload» lazy =»1″ />
Tested in Reactors
Boron neutron capture therapy (BNCT) was experimented with in the 1950s in the USSR, at the Institute of Medical Radiology in Obninsk, and the first clinical trials were conducted in 1951 in the USA. To do this, a special nuclear reactor was built at Brookhaven National Laboratory.
In subsequent years, research continued at other reactors in the United States and Japan. But the drugs available at that time did not allow achieving a high concentration of the boron-10 isotope in cancer cells. Currently, boronphenylalanine (BPA) and sodium boroncaptate (BSH) are used for targeted delivery of boron to a tumor, compounds that are safe for humans and are used as contrast agents for diagnosing tumors on magnetic resonance imaging.
Experiments in nuclear reactors have confirmed the effectiveness of BNCT for treating tumors brain and some other types of cancer. But conventional clinics need compact equipment. It turned out to be extremely difficult to create such a thing.
Based on an original idea
Scientists from the Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences (BINP SB RAS) have developed an installation based on a linear accelerator with a lithium neutron-generating target. The project was launched in 1998. In 2004, a pilot sample of the source was received. And in 2010, the first tests on cell cultures took place. Today it is the only facility in the world that produces epithermal neutrons (with energies from 0.5 eV to 10 keV) for scientific research.
It was shown to journalists during an excursion organized as part of the Popular Science Tourism initiative of the Decade of Science and Technology, which includes visiting the facilities of the Science and Universities national project.
«To solve the difficult task of creating a powerful neutron source of a certain physical range in a relatively the compact installation took more than twenty years,” says Sergey Taskaev, head of the BNCT laboratory, Doctor of Physical and Mathematical Sciences.
The initial element of the installation is a source of negatively charged hydrogen ions. The beam from it is sent to the tandem accelerator, where the ions change charge and accelerate. High-energy protons, moving in a magnetic field, hit the target — a copper disk with lithium sputtering. Upon collision with lithium nuclei, a nuclear reaction occurs, and neutrons are released, forming a therapeutic beam. crop-ratio=»0.701680672268908″ data-crop-width=»600″ data-crop-height=»421″ data-source-sid=»» class=»lazyload» lazy=»1″ />
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«Today, there are about a dozen different types of accelerators in the world, but none of them has been able to obtain a high-current proton beam, which is necessary for bombarding a target — a source of neutrons with specific energy characteristics. We were more successful than others, because we proposed a solution that provides the best quality of the beam,» Taskaev notes.
Another know-how is the design of a neutron-generating target. Physicists believe that the best way to generate epithermal neutrons is to bombard lithium nuclei with protons. However, for a long time it was believed that it was impossible to make a target from metallic lithium because of its softness, low melting point, and high chemical activity. Therefore, beryllium-9 and carbon-13 were used. But with them beams of charged particles should be much more powerful. Siberian scientists were the first in the world to successfully use a lithium target in a BNCT setup. =»0.975″ data-crop-width=»600″ data-crop-height=»585″ data-source-sid=»» class=»lazyload» lazy=»1″ />
Experiments on large mammals
Last year, the institute's researchers, together with colleagues from Novosibirsk State University (NSU), presented the results of a unique experiment on the treatment of domestic animals with malignant tumors. Cats and dogs were injected with a boron-containing preparation and irradiated at an accelerator neutron source. Everything was done in vivo, that is, directly on organisms.
“For half a century, quite a lot of experiments have been carried out around the world, but so far there have been no studies on large mammals. We are absolute leaders in this,” emphasizes Vladimir Kanygin, head of the laboratory of nuclear and innovative medicine of the Faculty of Physics, NSU, Candidate of Medical Sciences Vladimir Kanygin. “For more than three dozen animals were treated with BNCT».
“In general, the therapy has shown high efficiency in such formations as melanoma, glioblastoma, tumors of various localization, including those at the stage of metastatic lesions of distant organs and systems,” the scientist continues. “And both with traditional and newly developed drugs. the metabolism in the tumor is faster than in the body, respectively, and the accumulation of drugs is excessive. And the more malignant the formation, the more effective the method.»
Kanygin clarifies that they experimented only with spontaneous tumors (and not grafted, as in laboratory mice). Cats and dogs tend to have the same cancers as humans, so this study can be considered preclinical testing before human trials.
From idea to clinic
BNCT is most actively developed in Japan. Since 2020, they have been treating cancer with the help of accelerator neutron sources in two medical centers. In China, since October 2022, clinical trials have been ongoing at a hospital in Xiamen on a facility developed jointly by the Institute of Nuclear Physics of the Siberian Branch of the Russian Academy of Sciences and TAE Life Sciences (USA). In December, human studies were launched in South Korea.
Russia has a state program to transfer the accelerator neutron source built at the INP SB RAS into the clinical phase. By the middle of 2024, the institute's specialists should manufacture and send the source to the N. N. Blokhin National Medical Research Center of Oncology in Moscow, where preclinical and clinical trials are planned.
At the same time, for the first time in one study, both equipment and new compounds for targeted delivery of boron, developed in Russia to replace expensive imported ones. Trials should be completed in 2027, and BNCT will be available to patients by 2030.