Rays of health against cancer

How to cure a person with radiation

Egor Avdeev, N+1

Nuclear physics is changing the face of modern medicine – and for the better. Radionuclide-based drugs can significantly increase the chances of survival of patients with certain types of cancer. Even in cases where surgery is useless. In order to understand the process in detail, N+1 turned to Rosatom, the largest producer of radionuclides.

The patient drinks a glass with a clear solution and is cured of inoperable cancer. All the work is done by radionuclides, which are sources of ionizing radiation. With the solution, they penetrate into the human body and affect the cells affected by the disease.

Many modern radiopharmaceuticals, that is, drugs based on radioactive nuclides, work on this principle. They can purposefully destroy diseased cells using extremely small doses of radiation. This makes it possible not only to cure the patient, but also to restore his body after complex therapy in a matter of days.

Atoms for life

The principle of operation of radiopharmaceuticals is based primarily on the physical process of ionization, in which neutral atoms of a certain chemical element lose particles (for example, electrons), become active and turn into ions.

Ionizing radiation – in other words, radiation – comes from the atoms of the main chemical element that is part of the radiopharmaceutical. It is it that destroys the DNA of a malignant tumor. Under the influence of ionizing radiation, the properties of atoms inside the DNA of cells change, DNA chains begin to disintegrate, and the cancer cell loses its ability to reproduce. This is what doctors need, because one of the main properties of malignant tumors is uncontrolled and extremely rapid growth in the human body.

In addition to treatment, radiopharmaceuticals can perform another function – diagnostic. The cells of the body also react to weak ionizing radiation, which does not harm the body and at the same time is easily tracked by special tomographs, Valery Krylov, head of the Department of radiosurgical treatment with open nuclides of the A.F. Tsyba MRSC, who implements promising projects in the field of nuclear medicine with Rosatom, told N+1. The diagnostic capabilities of radionuclides can save thousands of lives long before cancer cells develop into serious tumors.

"Radionuclide diagnostics allows us to see malignant biological processes when the tumor has not yet led to structural changes in tissues," explained the radiologist. – It is thanks to the radionuclide radiation visualized on a gamma camera or PET tomograph that it becomes possible to detect changes occurring in organs and tissues at the cellular level. Other methods – for example, X–rays - usually do not allow to diagnose the disease at such an early stage."

The continuity of visualization processes and therapeutic effects is the main trend of radiooncology. "This is, in fact, the slogan of nuclear medicine: "We see what we treat, we treat what we see." It is very difficult to achieve this in other areas of medicine," Krylov added.

How to neutralize cancer with the help of physics

The "atomic" destruction of cancer DNA occurs in two ways. The first is the direct effect of radiation on the atoms of cancer DNA. The second is an indirect effect, through radiolysis of water, which makes up the cytoplasm of any biological cell. During "radioactive treatment", a large number of superoxide free radicals are formed in water (that is, ions of an oxygen molecule with an unpaired electron), and they cause damage to tumor cells.

The very ability of cancer cells to rapidly grow makes them especially vulnerable to radiation. The fact is that ionizing radiation most easily destroys the DNA structure when the cell is in the stage of chromosome division, where the main database of genetic data is stored. Since the cells of malignant tumors divide more often, they become the main target of ionizing radiation.

Both for treatment and for diagnosis, the drug must be directed to cancer cells. It is the targeting, that is, the target orientation, that is today considered an indicator of the perfection of radiopharmaceuticals, the production of which requires not only the calculated power of physics, but also an understanding of biological processes and many years of experience in medical practice.

Drugs deliver

The targeting of the drug can be achieved by different methods. "There is a wide scope for creativity here, because a lot of factors affect the delivery method. This is the type of cancer, and the specifics of the affected organ, and the properties of the radionuclide," explained Valery Krylov.

There are two main approaches to delivering radionuclide to cancer cells:

1. Create artificial transport molecules;
2. Use the metabolism of the human body itself.

The first approach resembles the selection of a key to a lock. "There is a specific receptor on the surface of a cancer cell that is not present on the surface of a healthy cell. A ligand (a chemical compound that "binds" to a certain biomolecule and produces the biochemical, physiological or pharmacological effects necessary for doctors – N+1) of a radiopharmaceutical can be attached to this receptor. A radioactive charge, in turn, is added to the ligand. Thus, the injected drug gets directly into the affected tissue," Krylov said.

The second approach allows the patient's body to make the "key selection" itself. This happens when the radionuclide itself naturally approaches certain types of cells. A textbook example is radioactive iodine, which is ideal for the treatment of thyroid cancer.

"This is due to the fact that thyroid cells produce thyroid hormones that contain iodine. On the surface of each thyroidyte there are special protein structures – sodium-iodine symporters, which "catch" the iodine in the blood plasma and put it inside the cell so that the cell would make hormones from it," Krylov explained. – What is radioiodotherapy based on? On the fact that the reporter cannot distinguish radioactive iodine from ordinary non-radioactive. First, we artificially create conditions for the so-called "hormonal hunger" so that these receptors greedily search for and capture iodine. Then we give the patient radioactive iodine. It gets inside the cells, and these cells die. This is how thyroid cancer is treated."

Cure with radiation: instructions

An approximate treatment regimen for thyroid cancer (not in advanced form and without metastases) using a radiopharmaceutical based on radioactive iodine-131 looks like this:

• The patient takes medications that cause a state of "hormonal hunger" of the thyroid gland.
• The patient drinks a diagnostic dose of radioactive iodine. Examination on a gamma camera will show how well the body assimilates iodine.
• The patient drinks a full–fledged drug - a solution of radioactive iodine. The solution looks like ordinary water.
• During therapy, the patient becomes radioactive. It is placed in a separate safe box with a special anti-radiation protection system.
• The solution begins to act: the thyroid gland takes radioactive iodine for ordinary and absorbs it. Ionizing radiation kills cancer cells.
• The patient is examined again with a gamma camera to see the effect of therapy.
• If the therapy has destroyed all the cancer cells, the patient undergoes hormone therapy.
• The patient is healthy and is regularly monitored by an oncologist.

"We need to understand that this is a very approximate scheme," Valery Krylov stressed. – Each oncological case is unique, and the doctor should prescribe treatment only after receiving complete information about the patient."

Russian radionuclides

On the basis of the two largest research institutes of the nuclear industry – the State Research Center of the Russian Academy of Sciences in Dimitrovgrad and the NIFHI named after. Karpova in Obninsk – GC Rosatom produces a whole line of radionuclides. Among them:

• Molybdenum-99
• Iodine-131
• Iodine-125
• Strontium-89
• Gadolinium-153
• Lutetium-177
• California-252

They are used as raw materials for the production of domestic medicines, as well as for export to more than 20 countries around the world. Among them are Germany, Hungary, Poland, Argentina, Brazil and China.

More precisely, smaller, safer

Russian radionuclide technologies began to develop in the Soviet period, since the 1920s. The first pharmaceutical based on radium-224 in the USSR was recommended, by the way, not for cancer, but for the treatment of diseases of the joints and spine. In the second half of the XX century, the Union was already considered one of the world leaders in the use of nuclear technologies in medicine – until the early 90s.

There were 650 radionuclide diagnostics laboratories operating in the country (conducting more than 1.5 million studies annually) and 20 radionuclide therapy departments (approximately 2,000 beds in total). Soviet research institutes produced approximately 140 radionuclides for industrial and medical purposes, as well as 38 full-fledged radiopharmaceuticals.

After the collapse of the USSR, the development of radiopharmaceuticals – as well as all nuclear medicine – was practically stopped. Systematic work in this area resumed only in the second half of the 2000s, with the creation of the Rosatom State Corporation, whose task was to restore the lost capacities of the country's nuclear industry.

Today, the company is striving to develop its infrastructure so that the production of domestic radionuclides, as well as pharmaceuticals and other equipment for nuclear medicine can become publicly available in Russia and enter the international market. Research institutes and plants in the structure of Rosatom produce raw radionuclide preparations, generators (devices for repeatedly obtaining a sterile solution containing radionuclides), as well as closed sources of ionizing radiation.

At the moment, Rosatom Group already occupies a leading position in the world in the production of radionuclides. They are effectively used to fight liver cancer, prostate cancer, as well as various metastases – especially in the bones, which often cause critically painful sensations in the patient. One of the modern promising methods is the use of radionuclides emitting alpha particles (radium-223, actinium-225, bismuth-213 and others). Alpha particles give more powerful radiation and at the same time have a much lower mileage than beta particles (they are most often used in modern radiopharmaceuticals), so they are able to deliver a more powerful and accurate blow to the tumor, while practically not touching the surrounding healthy tissues.

Scientists at the origins of radiopharmaceuticals

Nuclear medicine has been developing for more than 100 years. At the same time, the first research in this area was started not by doctors, but by scientists. French chemist and physicist Pierre Curie and his wife Maria Skladovskaya-Curie are considered the founders of this field of science. Their deadly experiments with the newly discovered chemical element radium (for example, Pierre Curie applied a radioactive compress on himself that burned his hand for 10 hours) laid the foundation for the development of not only nuclear physics, but also medical radiology. For their work, the scientists were awarded the Nobel Prize in Physics in 1903.

The Belgian scientist Charles Pesce (he is also called Charles Pecher in the American manner, since it was while working in the USA that he became famous as a radiologist), in turn, for the first time in the world, back in the late 1930s, tried the method of introducing a radioactive element - strontium – into the human body to alleviate the condition of a patient suffering from prostate cancer with bone metastases. This experiment can be called the first application of a radiopharmaceutical.

Rosatom Healthcare, an integrator in the field of radiation medical technologies in the structure of Rosatom State Corporation, is also developing other areas of nuclear medicine. For example, brachytherapy stands apart – that is, therapy based on "closed radionuclides". In this case, the sources of ionizing radiation are enclosed inside the shell – for temporary or permanent insertion into the affected organ. At the same time, radiation does not enter the environment, that is, it is not released from the body, both unchanged and in the form of metabolites.

An example of promising brachytherapy technologies is balls of yttrium–aluminosilicate glass with a size of about 30 microns. The unique irradiation technology in the Rosatom research reactor makes it possible to form the radioisotope yttrium-90 inside these microspheres. By introducing these balls into the patient's body, doctors can stop the growth of a malignant tumor in 90% of patients. Microspheres based on yttrium-90 have been produced since 2018 by the Russian company BEBIG with the support of the Federal State Budgetary Institution "NMIC of Radiology" of the Ministry of Health of Russia and the State Corporation Rosatom. In 2019, the first radioembolization operation based on this technology was successfully performed in Russia.

Rosatom State Corporation is also building up the potential for the production of equipment for radiation therapy, which treats the patient not from the inside, but from the outside. The company has developed a gamma-therapeutic complex of contact radiation therapy of a new generation AGAT-SMART and a linear accelerator "Onyx". The plans include the modernization of the EFATOM SPECT tomograph (gamma camera complex) and the production of a linear accelerator using the technology of the Swedish company Elekta.

Valery Krylov believes that Russian nuclear medicine technologies will grow rapidly in the coming years. "In 2009, a "nuclear medical revolution" happened in Russia. The standards of radiation safety were revised, which made it possible to more than double the capacity of the clinic," the scientist said. – Several more nuclear medicine centers were built – in Moscow, Tyumen, Krasnoyarsk, Arkhangelsk, Kazan. Therefore, now all efforts should be focused not only on increasing the number of "active" beds, but also on expanding the range of applications of radionuclide therapy, on the creation and introduction of new methods, on the development of the production of new radiopharmaceuticals."

Portal "Eternal youth" http://vechnayamolodost.ru