Method of realizing of neutron-catch therapy of oncological diseases

FIELD: nuclear medicine.

SUBSTANCE: method of realizing of neutron-catch therapy is based upon introduction of medicinal preparation into damaged organ or tissue of human body. Preparation has isotope with high cross-section of absorption of neutrons. Then damaged organ or tissue is irradiated by neutrons of nuclear reactor. Irradiation is performed with ultra-cold neutrons with energy of 10-7 eV and higher, which neutrons are released from cryogenic converter of neutrons of nuclear reactor and are delivered to damaged organ or tissue along vacuum neutron-guide, which neutron-guide has end part to be made in form of flexible catheter. Dosage loads are reduced.

EFFECT: minimized traumatism of healthy tissues of patient.

4 cl, 1 dwg, 1 tbl


The technical field to which the invention relates.

The invention relates to nuclear medicine, radiation therapy and can be used to implement neutron capture therapy, has found application in the treatment of cancer.

Prior art

In medical practice it is known that the available methods of cancer treatment is not effective enough - about 50% of cancer patients die from the disease. Mortality from cancer ranks second after cardiovascular diseases. Treatment of patients with malignant tumors refers to the priority of the state and scientific tasks in all developed countries of the world.

Today, for the treatment of cancer using three main methods of treatment: surgery, radiation therapy and chemotherapy. Among these methods, radiation therapy alone or in combination with other methods used in 40-75% of all cases of cancer, and there are trends of increasing this role in the near future.

One of the promising directions of radiation therapy is neutron therapy. It is preferable to other methods of radiation therapy in cases of locally advanced tumours of the head and neck, salivary glands, breast cancer. Advantages Nate is Onna therapy as demonstrated by recovery of primary tumor, and to overcome metastasis of malignant tumors. The positive effect is achieved not only by radical radiation exposure, but also due to the transition of a tumor in an operable form with subsequent surgical intervention.

Currently known neutron therapy, implemented in two versions - neutron-capture therapy (NRT) and fast neutron therapy (TBN). Especially promising neutron-capture therapy, based on the absorption of neutrons stable boron isotope10In (boron neutron capture therapy) or other element with a large capture cross section for neutrons and releasing considerable energy to the reaction products. The effectiveness of NRT data demonstrate the treatment of brain tumors of various etiologies: 35% of patients were alive five years after neutron therapy, while traditional treatment increases the life expectancy of only 8-10 months. Five-year survival of patients with mnogomorfnaya glio up to 50% without significant mental and physical degradation, while the best medical treatment gives only about 3% of cases five-year survival with significant mental degradation [Vphoto, Knezev, Whichshow and other Development of radiation technologies in the treatment of malignant tumors based on the neutron-to is based therapy. // Engineering physics No. 1, 2000, p.52-55].

The essence of the method of neutron capture therapy consists in the following. In the first stage, the tumor is injected drug containing chemical elements with a large capture cross section of thermal neutrons, such as boron, gadolinium, etc. Then the tumor is irradiated by thermal neutrons. When it absorbs a neutron, for example, boron isotope10In the reaction10In(n, α)7Li is formed α-particle and ion7Li, mileage which in biological tissue is about 10 μm. However, they emit energy of 2.3 MeV in the range of cells that contain a nucleus10In that leads to its destruction. This ensures the selective destruction of cancer cells while preserving normal tissue intact.

One of the most important requirements when conducting NRT is the reduction of radiation dose to the healthy parts of the patient's body and especially on the surface of the fabric. The focus of the neutron beam, filtering the background γ-rays and fast neutrons allows to minimize radiation doses. To the greatest degree requirements reduce the radiation dose γ-rays and fast neutrons satisfy tangent horizontal experimental channels of research reactors. The peculiarity of such channels is h what about their axis does not pass through the active zone of the reactor the source of fast neutrons and γ-quanta, which excludes the possibility of falling into the channel unscattered radiation. The admixture of fast neutrons and γ-radiation output from the tangent of the channel is less than the radial channel. The number of thermal neutrons must remain the same, if luminous surfaces are in identical conditions as the neutron flux in the reflector isotropic.

As a prototype of the selected reactor method for making NRT using beams of thermal neutrons derived from the active zone of the nuclear reactor, collimated and transported to the place of radiation therapy (Kulakov, VN, Khokhlov, V.F., Zaitsev, PHD, Portnow A.A. Way neutron capture therapy of malignant tumors and device for its implementation. RF patent 2141860, 06.02.1998]. In this way the biological object (a malignant tumor) to introduce boron - and/or gadoliniumbased connection in the extended form, and then fail to tumors derived from reactor neutrons. Field irradiation optimize energy and intensity using a system of filters and collimators.

The disadvantages of this method is unfavorable spatial distribution of neutrons in the body of the patient with the highest absorbed dose of neutrons on the surface of the body (the skin), rapid decrease in dose with depth is th - already at a depth of ˜2 cm neutron flux decreases in 2 times [Knezev, Art, Vassikin and other neutron capture therapy with thermal neutrons on the IRT MEPhI // Atomic energy, v.91, no 4, October 2001, str-314] and the background of fast neutrons and a companion γ-radiation, leading to radiation lesion of the normal tissues of the patient. This limits the use of the method only superficial or shallow-lying tumors. In addition, it is necessary to apply special measures to suppress the background of fast neutrons and a companion γ-radiation.

Disclosure of inventions

The task to be solved by the invention is to improve the implementation of neutron-capture therapy of malignant tumors.

The technical challenge is to meet the requirements of minimizing damage to healthy tissues of the patient by reducing the dose loads from associated γ-radiation and fast neutrons on the healthy parts of the body, the possibility of transport of the neutron beam to the deep lying tumors and effective impact on tumors of small size.

The problem is solved by the fact that the method of implementation of the neutron-capture therapy of cancer involves the introduction into the affected organ or tissue of a person's medical p is eparate, containing an isotope with a high cross section for the absorption of neutrons, and subsequent exposure of the affected organ or tissue by neutron nuclear reactor and irradiation are of ultracold neutrons with energies below 10-7eV, which is removed from the cryogenic Converter neutron nuclear reactor and deliver to the affected organ or tissue by vacuum neutron guide, the end part of which is made in the form of a flexible catheter.

In the private version of ultracold neutrons delivered to the affected organ or tissue, for example, the esophagus, oral cavity, bronchi, urinary tract, rectum.

In another private version of ultracold neutrons delivered to the affected organ or tissue through a flexible neutron guide-catheter, made for example of copper, or Nickel, or stainless steel.

In another private option as an isotope with a high absorption cross section of neutrons using lithium-6, or boron-10 or gadolinium-157.

Ultracold neutrons (UCN) have a speed of <10 m/s and a wavelength of from several hundreds to thousands of angstroms. One of the features of UCN is their ability to experience total reflection from the surface of condensed matter at all angles of incidence. The existence of the phenomenon of reflection of neutrons is very low energies and its ability DL is positive retention of neutrons in special containers was first noted in [for theoretical physics // JETP, 1959, T.36, str]. The phenomenon of total reflection of UCN, the possibility of long-term retention in closed volumes and transportation in the guide have been demonstrated in numerous experiments [III, Wpprotecto. Neutron physics. - M.: Energoatomizdat, 1997, s-342].

Time UCN storage in special containers is determined by the lifetime of the free neutron to βdecay and loss as a result of inelastic scattering or capture in collisions with the walls of the storage volume. Threshold energy for total reflection of neutrons from the surface at all angles of incidence is determined by the expression:


where the first member of the nuclear and the second magnetic scattering;

μ is the magnetic moment of the neutron;

ρ - density of nuclei;

b is the length of the coherent scattering;

A - mass number;

B - magnetic induction;

(±) for neutron spin parallel and antiparallel directions of the Century

When b>0 neutron originating from vacuum environment, meets positive barrier height of U. For most nuclei (Be, C, Mg, Fe, Cu, Zn, Pb, etc.) b>0 and only for some types of nuclei (Li, Mn, Ti, V) b<0. If E<U, the neutron is reflected and does not pass the boundaries. For almost all substances Eg˜10-7eV. U-value and critical speeds for different substances shown is in the table.

C (graphite)1,750of 5.83Gr. steel1,8206,05

Traditionally, the problem of producing ultracold neutrons is solved by extracting the low-energy tail of the Maxwell distribution of thermal neutrons at the exit of the moderator of a nuclear reactor. This uses the ability of UCN reflected from the surfaces of materials such neutrons are "locked" in the closed storage vessel, where they are routed from nuclear re ctor. However, because the share of very cold neutrons in thermal spectrum reactor is negligible, then "exit" ultracold neutrons in this approach is very limited.

There is another possibility of obtaining ultracold neutrons - cooling of the neutron after exiting the moderator of the reactor while passing through the cryogenic Converter (Converter) with low-temperature retarder, for example, superfluid helium, solid or liquid deuterium, liquid hydrogen. This is quite an efficient transfer of energy from neutron reactor the phonons (the quasiparticle representing the quantum of elastic oscillations of the environment), which significantly increases the proportion ultrahealthy neutrons. The Converter is located outside of the neutron reflector and the biological shield of the reactor to reduce thermal effects of radiation on the low-temperature moderator.

In the first experiments on the extraction of UCN from the reactor and the retention capacity of the neutron flux density was ˜0.1 g/(cm2·). Currently, the values of the flux density of UCN by five orders of magnitude higher. In the reactor of the Institute. M.laue and Plongeon in Grenoble flows UCN reach values of more than 104n/(cm2·). It is expected that by improving the technology of removing bundles of threads UCN will increase at least n is two or three orders of magnitude, to the level of 106-107n/(cm2· (C) [III, Wpprotecto. Neutron physics. - M.: Energoatomizdat, 1997, s]. Such values of density flows allow us to consider the possibility of practical use of UCN in various fields of science and technology, including for the needs of nuclear medicine.

It is believed that for the clinical application of NCT required flux of thermal neutrons density ˜10 n/(cm2· (C), and the admixture of fast neutrons should not exceed 1%. The degree of damage of tumor cells with neutron therapy Ntcan be estimated using the simple expression [Knezev, Art, Vassikin and other neutron capture therapy with thermal neutrons on the IRT MEPhI // Atomic energy, v.91, no 4, October 2001, str-314]:

where ρ10- concentration10In the tumor;

ϕ is the density of thermal neutron flux at the location of the tumor;

t - duration of exposure

σ - capture cross section of thermal neutrons by the nucleus10Century

At concentrations10In tumors of 30 µg/g and the capture cross section of 3.84-103barn [Radiative capture of neutrons. The Handbook. M.: Energoatomizdat, 1986] 1 hour exposure in each milliliter of its volume in the neutron flux of 109n/(cm2· (C) born more than 2-1010α-parts and recoil 7Li. Because in 1 ml of melanoma contains about 109cancer cells [Knezev, Art, Vaselkin and other neutron capture therapy with thermal neutrons at the reactor IRT MEPhI // Atomic energy, v.91, no 4, October 2001], each cell melanoma accounts for about 20 pairs α-particles and nuclei7Li. For the destruction of cancer cells with just a few α-particles. [P.M.Macklis, Y.J.Lin, B.Beresford et al. Cellular kinetics, dosimetry and radiobiology of alpha-particle immunotherapy: induction ofapoptosis. Radiat. Res. 1992. V.130. p.220-226].

As follows from expression (1), the degree of destruction of tumor cells depends not only on the magnitude of the neutron flux, but the cross-section of neutron capture, which for UCN is significantly higher than for thermal neutrons.

The capture cross section of ultracold neutrons for a 1/v absorber σandUCNcan be obtained by using the value of the cross section for neutrons arbitrary speed σand(E0=CT) using the following expression [III, Wpprotecto. Neutron physics. - M.: Energoatomizdat, 1997, s]:


where vkT- the speed of the neutrons at the temperature T;

vUCN- the speed of ultracold neutrons.

In the case of the so-called westcotts approximation using the capture cross section σand(E0=CT) for T=293,6°K, which then corresponds to the speed of the neutron v 0=2200 m/s Then the capture rate for UCN 1/v absorber will be equal to:


Because the rate of UCN ˜8 m/s [III, Wpprotecto. Neutron physics. - M.: Energoatomizdat, 1997, s], then the value of Ntfor UCN increases compared to neutrons of thermal energies 275 times.

The depth of penetration α-particles in biological tissue varies from 30 to 80 μm, which corresponds to several cell diameters. The density of ionization reaches -100 Kev/μm, so that the distance between two successive acts of interaction is comparable with the distance between the two strands of the DNA helix. Therefore, the probability to provide double the gap of the spiral with one α-particles is high enough, that automatically means high therapeutic efficacy.

Therapeutic effect of UCN capture can be estimated based on the power of the absorbed dose in the tumor [RF Patent 2212260 Way of planning neutron capture therapy. The authors Sealants, Sundarji, Wagrowska etc.]:

P=f·and(Cswelled.NA/M)·σaUCNE·K, [cGy/s]

where f is the flux density of UCN, n/(cm2·);

Withswelled.- concentration10In tumors, g/g tissue;

NA- the number of Avogadro;

M - molecular mass hee the practical element with a high capture cross section of thermal neutrons;

σandUCN- capture cross section of ultracold neutron, cm2;

E - the energy from the reaction products, MeV;

K=1,6·10-8cGy·g/MeV - coefficient of dimensional consistency.

At concentrations10In tumors of 30 µg/g, which is equivalent to≈2·1018nuclei10In/g, the capture cross section ≈106barn(10-18cm2) and the flux density of UCN ≈106n/(cm2·C)the power absorbed in tumor radiation dose R will amount to 4.2·10-2Gr/min At 2-hour exposure absorbed dose will exceed 5 Grams.

The dose necessary to kill cancer cells depends on the number of viable or count of clonogenic cells. So, for 1012cells necessary dose of 60 Gy to 108cells 40 Gy to 104cells 20 G and 100 cells, a dose of 10 Gy [Gerd-Jurgen Beyer alpha-emitting radionuclides - production and application. // The isotopes. Properties. The receipt. Application. Vol.2, M.: Fizmatlit, 2005]. However, it should be borne in mind that the allowable dose to the bone marrow is 1-5 GRS, for blood - 1-5 Gr for cardiovascular system - 10-20 Gy and for the whole body - 2 Gr. Lethal dose for subclinical tumor entities from 104cells - 20 Gr. To limit systemic dose on a body to Gr 2, you must ensure that the ratio of the dose distribution naked the narrow tumor/tissue of at least 10:1. For 100 cancer cells circulating in the blood, you need 10 G and, therefore, need to provide a ratio of 5:1. It is believed that the dose of 5 Gy is approaching the optimal level of radiation exposure for a malignant tumor.

Thus, the use of a beam of ultracold neutrons with a flux density of 106n/(cm2· (C) and the exposure time is not more than 2 hours provides the necessary therapeutic effect in the treatment of cancer.

The implementation of the invention

As the neutron source can be used in a nuclear reactor neutron flux in the core ˜1014n/(cm2·).

Neutrons from the reactor core is transported in the low-temperature Converter, representing cryogenic cryostat filled with liquid superfluid helium. The wall of the Converter is made of a material that provides a full reflection of UCN on the border.

After slowing down in the low-temperature Converter ultracold neutrons through a thin transparent window with b<0 are served in the vacuum neutron guide, which is transported to the experimental hall, where they conduct experiments or medical procedure for NRT. Vacuum neutron guide support to reduce the loss of neutrons in the process of diffusion. As the material of the walls are usually used honey is, Nickel or stainless steel.

The distribution of UCN in the neutron guide is similar to the flow of rarefied gas through the pipes and is characterized by the diffusion lengthwhere D is the diffusion coefficient, determined by the degree of specularity of the surface; T is the lifetime of a neutron in the neutron guide with respect to all processes: the absorption of neutrons walls and heated in a collision with the walls. Some UCN is lost in collisions with nuclei of the residual gas atoms and collisions with the walls of the neutron guide. The intensity UCN depending on the distance (1) to the Converter is given well-known exponential law exp(-1/Lc). For electropolished of the guide diameter ˜10 cm experimental values of Lcreach ≈10 m

Neutrons with energy E<Fgwhen moving inside a neutron guide will be repeatedly reflected from the walls, and the trajectory of the neutrons will follow the curves of the neutron guide. Even rotate 180° does not increase the "resistance" of the neutron guide. Neutrons with energy E>Fgexit of the neutron guide or just behind the Converter after the first collision with the wall (if the conditions of total external reflection are not met), or in the bend of the neutron guide after several reflections of them on the straight parts. Vero is tnost mirror reflection of UCN is of the order of 0.8 to 0.9.

The end part of the neutron guide is made in the form of a flexible catheters bellows - type corrugated thin-walled metal tube. At the end of the catheter is a thin, transparent window with b<0, through which ultracold neutrons come into a malignant tumor.

An example of the method

Method for making a neutron-capture therapy of cancer implement the system shown in the drawing. The installation consists of the reactor core 1, the neutron reflector 2, the horizontal channel 3, cryogenic Converter 4 - UCN source, vacuum neutron guide 5 for delivery of ultracold neutrons for medical procedures on neutron capture therapy, flexible neutron guide-catheter 6 for the supply of the UCN directly to the affected organ or human tissue.

As the primary neutron source selected experimental research reactor IR-8 thermal capacity of 8 MeV. The maximum neutron flux in the reactor core reaches 2·1014n/(cm2·).

Neutrons from the reactor core 1 and the tangent to the horizontal channel 3 with a diameter of 100 mm, made of aluminium, served in the low-temperature Converter 4, filled with superfluid liquid helium. The wall of the Converter is made of isoto is and Nickel Ni-58, providing a full reflection of UCN at the border. On the outside of the Converter is surrounded by thermal and radiation protection.

In the scattering on nuclei neutron superfluid helium loses almost all the energy. Neutrons with energies ˜10-7eV through a thin transparent window with b<0 are served in the vacuum neutron guide 5, which is transported to the experimental hall, where they conduct experiments or medical procedure for NRT. The residual pressure in the neutron guide is maintained at the level not higher than 1.3 to 10-2PA. As the material of the wall of the neutron guide use Nickel. The inner surface of the neutron guide is covered with a hydrogen-free oil Fomblin (F3CCF2OCF2CF5)nto reduce losses of UCN on the walls.

If necessary, the neutron beam can be blocked using neutron gates, representing opaque to ultra-cold neutrons screen made of Nickel.

The end part of the neutron guide is made in the form of a flexible neutron guide-catheter 6 bellows - type corrugated thin-walled metal tube. The catheter with a diameter of 10-15 mm ultracold neutrons screen delivered directly to the diseased organ in the esophagus, oral cavity, bronchi, urinary tract, rectum, or other way. Neutron flux at the output of the C of the catheter reaches values ˜ 106n/(cm2· (C)that provides the necessary doses for operations on neutron capture therapy.

The proposed method of implementation of invasive neutron capture therapy of malignant tumors allows for the use of beams of ultracold neutrons to minimize damage to healthy tissue of the patient to be transported neutron beam to deep-seated tumors, effectively influence tumor of the small size.

1. Method for making a neutron-capture therapy of cancer, comprising introducing into the affected organ or tissue of a person medical preparation containing an isotope with a high absorption cross section for neutrons and subsequent exposure of the affected organ or tissue by neutron nuclear reactor, characterized in that the irradiation leads ultracold neutrons with energies below 10-7eV, which is removed from the cryogenic Converter neutron nuclear reactor and deliver to the affected organ or tissue by vacuum neutron guide, the end part of which is made in the form of a flexible catheter.

2. The method according to claim 1, characterized in that ultracold neutrons delivered to the affected organ or tissue, for example, the esophagus, oral cavity, bronchi, urinary tract, rectum.

3. The method according to claim 1, the tives such as those the flexibility of the catheter is performed, for example, of copper, or Nickel, or stainless steel.

4. The method according to claim 1, characterized in that as an isotope with a high absorption cross section of neutrons using lithium - 6, or boron - 10 or gadolinium - 157.


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13 cl, 4 dwg

Neutron generator // 2273118

FIELD: nuclear engineering, in particular, engineering of neutron generators, possible use, for example, in neutron tubes for logging research.

SUBSTANCE: neutron generator additionally includes sprayer of hydrogen-active metal onto target. Metal is applied during breaks in generator operation, being saturated with deuterium and tritium from gas located within the tube. Target with diameter D is positioned in plane of target base. Sprayer has frame made of vacuum dielectric material, wherein grooves are made, where with possible reciprocal movement in plane perpendicular to pipe ignition electrodes are positioned. Mobility of ignition electrodes allows by means of corrugated pipes without disruption of vacuum to alter gap between them and sprayed electrode from outside the pipe, to achieve guaranteed disruption of gap and generation of arc under effect from voltage of sprayer electric power. Sprayed electrode is made in form of a truncated cone provided with aperture. Sprayer also has protective metallic cover in form of hollow truncated cone, top of which is positioned in target hollow. Selection of angle between generatrices of cover in cross-section, passing through its axis, being equal to 2,2 arctg(0,5(Dk-D)/H), where Dk - internal diameter of cover in cross-section coinciding with plane of top of sprayed electrode cone, D - diameter of substrate, and H - distance from this plane to target plane.

EFFECT: increased lifetime of target, possible increasing of neutron output of generator by increasing flow of deuterons bombarding the target.

1 cl, 3 dwg

Vacuum neutron tube // 2267181

FIELD: neutron engineering; production of devices for generation of a fast neutrons stream.

SUBSTANCE: the invention is pertaining to production of devices for generation of a fast neutrons stream, in particular, to production of vacuum neutron tubes. The invention presents the vacuum neutron tube, which has been made in the form of a hermetic body with located inside it a source of ions representing a system "an electron projector - an emitting ions anode" and a neutron-forming target. The internal space is divided into two sealed volumes by a diaphragm with a hole, in which there is a hermetically fixed anode facing the target. In one of the volumes there is a cathode of the electron gun, and in the other - the target is placed. The technical result of the invention is simplification of the vacuum neutron tube design, increased its effectiveness due to an increased emissive capacity of the cathode.

EFFECT: the invention ensures simplification of the vacuum neutron tube design, its increased effectiveness and emissive capacity of the cathode.

8 cl, 1 dwg

The invention relates to the field of nuclear engineering

The invention relates to the field of devices for GIW, in particular downhole neutron generators

Vacuum neutron tube // 2228554
The invention relates to a device for generating a pulsed fast neutron flux

FIELD: production of radioactive isotopes.

SUBSTANCE: proposed method for producing nickel-63 radioactive isotope from target within reactor includes production of nickel-62 enriched nickel target, irradiation of the latter in reactor, and enrichment of irradiated product with nickel-63, nickel-64 content in nickel-62 enriched target being not over 2%; in the course of product enrichment with nickel-63 nickel-64 isotope is extracted from irradiated product.

EFFECT: enlarged scale of production.

1 cl, 2 tbl