Devices for generating, slowing, and configuring neutron beams for neutron capture therapy.

Abstract

The present invention provides devices for generating, slowing, and configuring neutron beams for neutron capture therapy. [Solution] The device for generating, slowing, and constructing a neutron beam comprises an inlet opening 1 into which a proton beam is directed; a target 2 into which the proton beam is accelerated to generate a neutron beam; a moderator 3 that brings the neutrons to an energy in the epithermal range; a reflective cover 4 surrounding the moderator; a filtration stage 5; an outlet opening for the neutron beam; and a shield 7 for suppressing neutron and gamma-ray radiation that does not exit the device through the outlet opening. The filtration stage comprises at least three layers that filter fast neutrons, thermal neutrons, and gamma-ray radiation, respectively.

Description

[Technical Field]

[0001] The present invention generally relates to devices for generating, slowing, and structuring beams, and more specifically to neutron beams for neutron capture therapy. [Background technology]

[0002] Boron neutron capture therapy (commonly abbreviated as BNCT) is a type of experimental cancer radiation therapy that is unique in that it is selective at the cellular level, allowing for different and controllable doses to healthy tissue and tumor tissue. In this way, tumor cells can be killed without damaging surrounding healthy tissue. BNCT technology primarily involves pre-treating boron compounds ( 10 This method involves irradiating patients who have been administered (B is highly likely to be captured by neutrons) with neutrons. Generally, the neutron beam is generated by a nuclear reactor, or more recently, by a particle accelerator. Boron is favorably bound to cancer cells, so when neutrons react with boron, a nuclear reaction occurs that kills or severely damages the cancer cells, while cells in adjacent tissues are largely undamaged.

[0003] To make boron neutron capture therapy feasible, a neutron beam of a specific quality is required. This neutron beam must be epithermal (i.e., between 0.5 eV and 10 keV) and have an intensity appropriate to the type of tumor being treated. Furthermore, the beam must minimize mixing of thermal neutrons (below 0.5 eV) and fast neutrons (above 10 keV) and gamma-ray radiation. Similarly, the treatment must account for the thermalization of epithermal neutrons (i.e., the process by which the neutron's energy decreases as it penetrates tissue, reaching a thermal peak at a depth of 3-6 cm). Additionally, the neutron beam must have low diffusion to maximize the radiation dose to the tumor while minimizing the dose to other parts of the patient's body. These conditions are standardized in International Atomic Energy Agency (IAEA) Technical Document 1223 (D. Rorer et al., "Current Status of Neutron Capture Therapy, IAEA TECDOC 1223," International Atomic Energy Agency, Vienna, 2011).

[0004] Recent technologies (e.g., [I. Porras et al., "Perspectives on Neutron Capture Therapy of Cancer," CERN Proc., 1, 295-304, 2019] and [Torres-Sanchez et al., "On the upper limit for the energy of epithermal neutrons for Boron Neutron Capture Therapy," Radiation Physics and Chemistry, 156, 240-244, 2019]) have shown that the optimal neutron energy for BNCT therapy is within a range of several keV (1-10 keV) depending on the tissue being treated. Furthermore, to ensure the applicability of the neutron beam in BNCT therapy, it is recommended to measure the following quality factors, in particular, regarding the tissue penetration capacity of the radiation: - Advantage Depth (better known as AD): this is defined as the depth within the tissue at which the radiation dose received by the tumor equals the maximum dose deposited in healthy tissue. This parameter determines the recommended maximum application depth for BNCT treatment. - Treatable Depth (TD): this indicates the depth at which the dose to tumor tissue is twice the maximum dose deposited in healthy tissue. It therefore determines the area in which BNCT treatment can be most efficient. - Advantage Depth Dose Rate (ADDR): this is equivalent to the maximum dose rate in healthy tissue. Once the treatment time is determined, this allows the maximum dose received by healthy tissue to be known. - Therapeutic Ratio (TR): this is given by the ratio between the maximum dose in the tumor and the maximum dose in healthy tissue. It is therefore a parameter that should be maximized to prevent damage to healthy tissue.

[0005] Furthermore, the IAEA defines another set of recommendations for parameters relating to the energy of the generated neutrons: - Epithermal flux (φ epi ): this measures the flux of epithermal neutrons incident on the tissue. The recommendation states that this parameter must be greater than 10 9 epithermal neutrons (n) per square centimeter per second (unit: n / cm 2 s). - Ratio between thermal neutrons and epithermal neutrons: φ th / φ epi , where φ th is the thermal neutron flux, which must be less than 0.05 when expressed on a per unit basis. - Ratio between total current (J n ) and total flux: J n / φ n , which relates to the direction and diffusion of the generated beam. The larger this parameter, the better focused the beam is, and the less irradiation there is to healthy tissue in the vicinity of the tumor tissue. This parameter is preferably greater than 0.7. - Fast neutron dose per epithermal neutron (D fast): This parameter is 2.10 -13 Gy·cm 2 It is preferable to minimize it to less than / n. - Gamma radiation dose per epithermal neutron (D γ ): As above, it is preferable to minimize this dose in order to reduce the radiation received by the patient. The value is 2.10 -13 Gy·cm 2 It must be less than / n.

[0006] To compare various BNCT treatment devices, simulations using tissue reference models are often employed, such as the ICRU4 standard tissue model (recommended by the International Commission on Radiation Units and Measurements) and the Snyder brain model (see WS Snyder et al., "Estimates of absorbed fractions for monoenergetic photon sources uniformly distributed in various organs of a heterogeneous phantom," Oak Ridge National Lab, Tenn., J. Nucl. Med. 10: Suppl. No. 3, 7-5, 1969).

[0007] In the past, BNCT was carried out using neutron sources from nuclear reactors. For reference, mention should be made of the FiR-1 facility (a nuclear reactor located in Helsinki, which has now been decommissioned) and the KURRI facility in Kyoto. However, nowadays, as a result of the development of low-energy high-intensity accelerator technology, BNCT can be implemented in hospital-based installations (see Brugger, R. M et al., "Rapporteurs' report. Neutron beam design, development, and performance for neutron capture therapy", Springer, Boston, MA, 1990, pp. 3-12). For example, the "Cyclotron Based Epithermal Neutron Source", abbreviated as C-BENS and located in Kyoto, is a cyclotron accelerator-based BNCT facility for generating epithermal neutron sources, and is currently in operation.

[0008] In recent years, as disclosed in A. J. Kreiner et al., "Present status of accelerator-based BNCT", Reports of Practical Oncology & Radiotherapy 21.2, 2016, pp. 95-101, 7 Li(p,n), 9 Be(p,n) or 9 like Be(d,n), various reactions for neutron generation are being tested, and efforts are being made to search for an optimal neutron beam. However, the neutrons generated by these reactions exceed the energy required for BNCT treatment (on the order of hundreds of keV to MeV). Therefore, there exists a need for a device for neutron beam generation, moderation and configuration (DPMC) for neutron capture therapy that can adapt the generated neutrons to therapeutic needs and appropriately satisfy all IAEA recommendations that only consider neutrons in the epithermal range (i.e., 0.5 eV to 10 keV, which is optimal for BNCT treatment). Summary of the Invention Problem to be Solved by the Invention

[0009] As explained in the preceding chapter, in the field corresponding to devices for production, moderation and configuration of neutron beams (DPMC), there exists a need to develop a device that can satisfy all International Atomic Energy Agency (IAEA) recommendations considering only neutrons in the epithermal range (0.5eV~10keV). The present invention provides a solution to the above-mentioned need by means of a device that can provide an energy range which is more suitable and safer for use in boron neutron capture therapy.

[0010] More specifically, the main object of the present invention relates to a DPMC for neutron beams based on the production of neutrons from a proton beam, whereby a neutron flux exceeding 109n / (s cm2) between 1eV and 20keV can be obtained, while maintaining the following: (i) the thermal neutron flux is less than 5% of the total flux; (ii) the dose generated by fast neutrons is less than 2 × 10-13Gy cm2 per neutron between 1eV and 20keV; (iii) the dose generated by secondary photons is less than 2 × 10-13Gy cm2 per neutron between 1eV and 20keV. Means for Solving the Problem

[0011] A DPMC for a neutron beam based on the production of neutrons from a proton beam, - an inlet opening through which a proton beam is directed; - a target that interacts with a proton beam via a nuclear reaction to generate a neutron beam that defines a main propagation axis; - a cooling module for cooling the target so as to prevent melting of the target; - a moderator in contact with the target, wherein neutrons produced by the nuclear reaction are moderated to energies in the epithermal range; - a reflective cover surrounding the moderator for redirecting diffused neutrons back to the main axis and increasing the epithermal neutron flux; - a filtration stage comprising at least a fast neutron filtration layer, a thermal neutron filtration layer, and a gamma radiation filtration layer; - An outlet opening for a neutron beam, which is in contact with a filtration stage, - A shield positioned around the exit opening to suppress neutron and gamma-ray radiation that does not exit the device through the exit opening, The device is equipped with the above-mentioned properties. Depending on the composition and dimensions of this device, a neutron flux having the above-mentioned characteristics can be obtained.

[0012] The DPMC is characterized in that a filtration stage acts on the neutron beam before the neutron beam exits the device through the outlet aperture. The resulting neutron beam can be applied, for example, to patient tissue.

[0013] In a preferred embodiment of the present invention, the proton beam that strikes the entrance opening is obtained by a particle accelerator, and the proton beam is accelerated toward a target made of a metallic material in order to generate neutrons.

[0014] In another preferred embodiment, the target is 7 It contains Li, and the nuclear reaction with the incident proton beam is 7 Li(p,n) 7 It is Be.

[0015] In certain embodiments, the moderator includes at least one of the following materials: graphite, D2O, AlF3, CaF2, Li2CO3, MgF2, Al2O3, and Fe. In particular, when the energy source (proton beam) is a low-energy source, the use of MgF2 is preferred. When the source is a high-energy source, it is preferable to gradually replace MgF2 with AlF3, and then replace both with CaF2 and Fe, respectively.

[0016] In other preferred embodiments, the speed reducer has at least one portion of one of the following geometric shapes: cylindrical, conical, pyramidal, or truncated pyramidal.

[0017] In some preferred embodiments of the present invention, the reflective cover comprises at least one of the following materials: Ni, Pb, BeO, and Bi.

[0018] In some advantageous embodiments of the present invention, the fast neutron filtration layer of the filtration stage comprises at least one of the following materials: Al, Fe, and Ni.

[0019] In other specific embodiments of the present invention, the thermal neutron filtration layer of the filtration stage is made of the following material: 10 B, 6 It contains at least one of Li, Gd, Cd, or LiF. This reduces the excessive thermal irradiation that healthy surface tissues receive during neutron beam application. Thermal neutrons are not useful for intracellular applications because they mostly do not penetrate deeply into tissue and are only applicable to surfaces or shallow trauma. Gd and Cd are examples of materials with the largest thermal trapping cross-section, and would be optimal to use for thermal neutron removal if it were not necessary to minimize gamma-ray emission generation. In either case, gamma-ray emission generation is significant, suggesting a thicker Pb or Bi as a gamma-ray emission filter. Alternatively, this filtering layer may be placed partially before the deceleration, in which case the gamma-ray emission would be partially attenuated by passing through the rest of the material, but in such a case its effect as a thermal neutron attenuator would be reduced.

[0020] In another preferred embodiment of the present invention, the gamma-ray emission filtration layer of the filtration stage comprises at least one of the following materials: Pb, Bi. This reduces contamination of the neutron beam obtained in the present invention by gamma-ray emission.

[0021] As a result of the three layers described above, which comprise at least the filtration stage of the present invention, radiation sources other than epithermal neutrons are reduced. This results in a spectrum of the generated neutron beam that exhibits very high energy selectivity, with a maximum value in the 2-3 keV range, making it highly suitable for neutron capture therapy (more specifically, BNCT).

[0022] According to some specific embodiments of the present invention, the exit aperture for the neutron beam has at least one portion of one of the following geometric shapes: cylindrical, conical, pyramidal, or truncated pyramidal. In this way, the diffusion of the resulting neutron beam is reduced.

[0023] In certain advantageous embodiments of the present invention, the exit aperture (6) for the neutron beam is provided with a movable closure for stopping irradiation.

[0024] In another embodiment of the present invention, the shield placed around the exit aperture for the neutron beam is made of the following material: LiF, 6 It comprises at least one of LiF, B4C, polyethylene, Pb, and Bi. In other preferred embodiments, the shield comprises only Pb and lithified polyethylene. In some more advantageous embodiments, the Pb layer and the lithified polyethylene layer contain natural LiF and 6 Two additional layers of Li-enriched LiF are added. As a result of the shielding, most of the neutrons diffused from the main axis and the associated gamma-ray emissions are suppressed in order to reduce the amount of radiation received by normal tissue or areas close to the irradiated tissue (where the residual radiation received should be as minimal as possible). B4C is, 10 Because it contains B, it is a commonly used material and is a solid.

[0025] A preferred use of the neutron beam DPMC of the present invention is in boron neutron capture therapy. As a result of the filtration stage, prior to the emission of the neutron beam of the present invention, the neutron beam has a spectrum suitable for its use in this type of therapy.

[0026] Throughout this document, the terms “comprises” and their derivatives should not be understood exclusively, but rather in a sense that allows for the possibility that what is defined may include additional elements or steps. [Brief explanation of the drawing]

[0027] To complete the description of the present invention, a set of drawings, which are an integral part of this description and illustrate preferred embodiments of the invention, are provided. The drawings should be interpreted in a non-limiting illustrative manner and are described in detail below. [Figure 1] This figure shows a preferred embodiment of the present invention in a two-dimensional axial cross-section, illustrating the main dimensions of the device and the materials used to assemble it. [Figure 2] Figure 1 shows a three-dimensional view of the present invention. It has a radial cross-section to visualize the distribution of materials and layers within it. [Figure 3] This figure shows the neutron spectra at various points from the Li source to the outlet aperture of the present invention to demonstrate how appropriate material selection minimizes thermal and fast neutron fluxes to reach a spectral maximum of 2–3 keV without reducing epithermal neutrons. The epithermal range (0.5 eV–10 keV) is shown in gray. [Figure 4] This figure shows the final emission spectrum obtained at the exit aperture of the present invention on a logarithmic scale, compared to two reference BNCT treatment facilities: FiR-1 in Helsinki, Finland, and C-BENS in Kyoto, Japan. The epithermal range (0.5 eV to 10 keV) is shown in gray. [Figure 5] Figure 4 shows the final spectrum of radiation obtained at the outlet aperture of the present invention, compared to each facility, on a linear scale. The epithermal range (0.5 eV to 10 keV) is shown in gray. [Figure 6] A figure showing the lateral profiles of neutron flux (epithermal, thermal, and fast) and gamma-ray emission in the radial direction at the outlet opening of the present invention, on a logarithmic scale.

[0028] The series of reference numbers corresponding to the following elements are associated with the drawings mentioned above. (1) Entrance opening (2) Target (3) Moderator (4) Reflective cover (5) Filtration stage (6) Exit opening (7) Shield (W1) The thickness of the air in the direction of the beam from the last filtration layer (5) to the inlet opening (1). (W2) Thickness of the moderator (3) in the direction of the beam from the target (2) to the filtration stage (5) (L1) Thickness of the fast neutron filtration layer (L2) Thickness of the thermal neutron filtration layer (L3) Thickness of the gamma-ray emission filtration layer (L4) Thickness of the front or front portion of the speed reducer in an embodiment in which the diameter of the speed reducer decreases as it approaches the exit opening. (L5) The diameter of the speed reducer (φ3) is constant, and the thickness of the rear of the speed reducer is constant. (L6) Thickness of the cover (4) from the moderator (3) to the inlet opening in the direction of the beam. (φ2) Diameter of the rear of the speed reducer (φ3) Diameter of cover (4) (φ4) Diameter of the device including the side shield (7) (R1) Inner diameter of the collimator of the front shield (7) (R2) Outer diameter of the collimator of the front shield (7) [Modes for carrying out the invention]

[0029] Figure 1 shows a preferred implementation of the present invention having axial symmetry and a cylindrical-conical shape. First, a proton beam must be accelerated to 2.1 MeV (however, other values ​​may be used) by an accelerator (not shown), and all IAEA recommendations are satisfied by directing the proton beam through the inlet opening (1) or directional tube of the present invention. In a proton beam of this energy, the neutrons produced by the present invention have an average energy of 108.4 keV and a maximum energy of 350.4 keV. Next, the proton beam is directed to a target (2) (in this case, a lithium (located at the end of the directional tube of the accelerator) 7 Li(s) collide with a sheet and trigger a nuclear reaction. 7 Li(p,n) 7Neutrons are produced by Be. The proton beam is directed along the main axis. However, other preferred embodiments of the present invention involve other nuclear reactions for producing neutrons (for example) 9 The invention may also include Be(p,n)). Furthermore, the present invention includes a cooling module for cooling the target (2) (not shown, but necessary to prevent the target (2) from melting due to the high temperatures that may occur).

[0030] A core of moderator (3) is positioned surrounding the lithium target (2), extending in the front direction and on both sides, from the target (2) to the filter (5) in the front direction, with a thickness (W2) of 21.80 cm ± 10% (preferably 21.8 cm). Preferably, the moderator is manufactured with MgF2. Other materials that can be used as moderator (3) are combinations of Al, Mg or Ca metal with F, carbon in the form of graphite, or water (H2O or heavy water D2O). These materials are selected based on their neutron interaction properties. Therefore, isotopes with large elastic cross-sections and small absorption cross-sections are required. Neutrons can gradually lose energy through elastic collisions. The energy loss due to these collisions is greater for lighter isotopes such as hydrogen or deuterium, or carbon. The suitability of elements Al, Mg, Ca, or F lies primarily in their energy resonance in the tens to hundreds of keV range (which reduces the amount of high-energy neutrons transitioning to the epithermal range via moderation). MgF2 is preferred over other materials due to its relatively large elastic cross-section, while generating less gamma-ray radiation per capture than other materials such as water. Furthermore, each nucleus is not so light that it loses most of its energy in each collision, allowing neutrons to lose their energy much more slowly and controllably. Other metals such as Al or Ca have higher energy resonances, making them less suitable as low-energy sources than Mg. In other preferred implementations of the present invention, the moderator can be fabricated from at least one of the following materials: D2O, Al2O3, Li2CO3, or other materials known to those skilled in the art with equivalent or similar properties. In Figure 1, the moderator (3) includes a cylindrical portion and another conical portion. However, in other preferred embodiments, the speed reducer (3) comprises at least one portion or profile having one of the following geometric shapes: cylindrical, pyramidal, truncated pyramidal, or conical.

[0031] Preferably, a reflective cover (4) (made of a material having a large elastic impact cross-section and a high mass number) is placed around the moderator (3), so that neutrons do not lose more energy in these collisions, and the probability of back-facing collisions is higher, thereby allowing neutrons to recover toward the core of the moderator. Thus, the reflector redirects the diffused neutrons toward the main axis of the neutron beam, thereby increasing the epithermal neutron flux. In the rear portion, from the moderator to the inlet opening, the cover (4) has a thickness of 25.00 cm ± 40% (L6) in the direction of the beam.

[0032] Furthermore, the moderator covers the target and a portion of the accelerator tube up to the rear (beam inlet). In a preferred embodiment, the total thickness of the moderator (L4+L5) is set between 24.64 cm and 36.96 cm.

[0033] Furthermore, the material of the reflector cover (4) must absorb the gamma-ray radiation generated during the deceleration process. For this reason, a material with a high atomic number is ideal for this task. In this method, the optimal materials for this function are lead and bismuth. Pb has a larger elastic impact cross-section than Bi and has generally been used as a reflector (except in the front direction where beam diffusion is a factor to consider). By increasing the thickness (L6) of the Pb layer in the radial and rear directions, more neutrons that have escaped from the core of the moderator (3) can be recovered. This relationship is maintained until the maximum thickness is reached at which the increase in epithermal neutrons saturates.

[0034] The filtration stage (5) (also surrounded by the reflective cover (4)) is positioned after the core of the moderator (3). The filtration stage (5) provides additional filtration of the neutron spectrum (fast and thermal neutrons) that do not contribute to BNCT therapy, and functions to reduce gamma-ray emission while minimizing the impact on the epithermal neutron flux. Preferably, the filtration stage (5) comprises at least the following layers: - Fast Neutron Filter Layer: This layer complements the deceleration and essentially performs the function of filtering the resulting neutron spectrum by selectively removing some of the fast neutrons through their resonance. The thickness of this layer (L1) is 1.00 cm ± 15%. In Figure 1, this layer consists of an aluminum sheet with a thickness of 1 cm. However, other elements such as Fe or Ni may also be suitable. - Thermal neutron filtration layer: The purpose of this layer is to suppress thermal neutrons in the beam. The deceleration process later generates a considerable amount of thermal neutrons (which must be removed from the beam before it can be used for BNCT therapy). Li is a material with a large thermal trapping cross-section. This property makes it an ideal thermal neutron filter. The thickness of this layer (L2) is 0.20 cm ± 20%. In particular, in the implementation shown in Figure 1, this layer is a LiF sheet with a thickness of only 2 mm, yet it is capable of removing more than half of the thermal neutron flux that reaches it. Other materials that can be used for this thermal neutron filtration layer are B and Cd (these have relatively large capture cross-sections and generate gamma-ray emission in exchange, requiring a large amount of Pb or Bi in the reflective cover (4) to remove this). - Gamma-ray emission filtration layer: This layer is designed to reduce gamma-ray emission while minimizing its impact on the epithermal neutron flux. The thickness of this layer (L3) is 1.00 cm ± 10%. In Figure 1, this layer consists of a 1 cm thick Bi sheet, which allows for a larger neutron flux with lower diffusion.

[0035] Preferably, the gamma-ray emission filtration layer is positioned last along the direction of flight of the generated neutron beam. More preferably, the thermal neutron filtration layer and the gamma-ray emission filtration layer are positioned in this order along the direction of flight of the generated neutron beam.

[0036] Figure 1 shows that the filtration stage (5) comprises layers of aluminum, LiF, and Bi in that order, along the direction of flight of the generated neutron beam. However, each of the above layers can be arranged in any order that is technically possible and can also be replaced with parts of the moderator block. Another preferred embodiment of the present invention comprises one or more of the layers included in the filtration stage (5).

[0037] As a result of the filtration stage (5), the resulting neutron spectrum is suitable for BNCT therapy (fast neutrons and thermal neutrons are filtered out, the thermal neutron flux is kept below 5% of the total flux, and residual gamma-ray emission is also removed).

[0038] Next, an exit aperture (6) is positioned to determine the shape and focus of the beam. In particular, it has a cylindrical-conical portion as shown in Figure 1. For this purpose, the aperture is provided with a collimation cone (preferably also made from Pb, thereby allowing the neutron beam to be shaped considering the slope of the cone's generatrix). If the slope is too large (i.e., a very elongated collimation cone), it will excessively reduce the epithermal flux. Conversely, if the slope is too low (i.e., a very flat cone), it will produce excessive diffusion of the beam. The neutron beam usable for BNCT therapy exits through the air-filled exit aperture (6). It should be noted that in some preferred embodiments of the present invention, the exit aperture (6) is provided with slits and / or protrusions. Similarly, in other advantageous implementations, the aperture (6) is provided with a movable closure (also called a beam shutter) having a double Li and Pb layer that can be remotely operated to stop irradiation.

[0039] Finally, a shield (7) consisting of various layers is positioned to absorb neutrons that would otherwise be emitted elsewhere through parts other than the exit opening 6, and to protect the patient from gamma-ray radiation. Behind the exit opening (6), various materials are positioned to absorb neutrons that would otherwise be emitted from the invention in an uncontrollable manner. As shown in Figure 1, this shield (7) comprises at least two layers, each consisting of one of the following materials: - Lithium-ionized polyethylene as a coating for the reflective cover (4) (for absorbing thermal neutrons) 6 (Including Li-enriched polyethylene). Since the polyethylene contains hydrogen, the neutron energy can be rapidly reduced to the thermal range, 6 Li traps these without generating gamma-ray radiation. As a result of this layer, neutrons that could potentially emanate in these directions are thermalized and absorbed as an additional radiation protection measure. - Lead used to absorb gamma-ray radiation.

[0040] Shield (7) has a sufficiently high ratio 6 If mixing with Li is achieved, it may contain only the two layers described above (the Pb layer and the lithium polyethylene layer). Alternatively, 6 To increase the concentration of Li isotopes, the following two additional layers may be used: the natural LiF layer and 6 Li-enriched LiF layer (which, along with the natural LiF layer, prevents contamination of the neutron beam resulting from contributions off-axis).

[0041] Another preferred implementation of the present invention uses the above-mentioned materials: lithium polyethylene, lead, LiF, 6 There may be one or more layers of the Li-enriched LiF shield (7). In other implementations, the lithified polyethylene may be replaced with borate-treated polyethylene.

[0042] Each layer of the shield (7) is described above in the sense that it will be penetrated by the neutron beam. However, they can be arranged in any order that is technically possible. Thus, the exit opening (6) is covered with lead and LiF layers in both its conical and cylindrical cross-sections. However, it should be noted that the arrangement of the layers of the shield (7) shown in Figure 1 is merely illustrative and may vary depending on the design requirements.

[0043] In summary, the DPMC must be able to generate a high-flux epithermal neutron beam while minimizing heat and fast neutron flux. The optimal neutron energy for BNCT is several keV, and since it is possible to treat deep tumors, the maximum value of the spectrum must be within this energy range. Similarly, beam contamination by gamma-ray emission must be avoided as much as possible. Finally, the neutron beam must have good collimation and not be too diffuse. In other words, the generated neutrons must be emitted forward, and the beam must not spread excessively after exiting through the exit aperture (6). It should be noted that in this invention there are two different gamma-ray emission filters, each with a different function: the layer included in the filtration stage (5) filters the radiation for the beam that is to be emitted through the exit aperture (6) and used for treatment, while the gamma-ray emission filter included in the shield (7) only affects neutrons diffused from the main axis.

[0044] In a preferred embodiment of the present invention shown in Figure 1, the design is generated from two parameters that must be pre-assigned: A (14 cm) and φ1 (8 cm). The remaining parameters represent the optimal dimensions of the design. However, the DPMC is operable within a specific acceptable range of the above parameters, and the optimal range for each parameter is shown below in centimeters, along with the percentage variation that is acceptable without substantially degrading its operation: φ2 (50, ±10%), φ3 (120, ±15%), φ4 (130, ±20%), R1 (10, ±10%), R2 (45, ±50%), W1 (19.80, ±10%), W2 (21.80, ±10%), L1 (1.00, ±15%). %), L2(0.20,±20%), L3(1.00,±10%), L4(6.20,±10%), L5(24.60,±10%), L6(25.00,±40%), L7(57.00,±20%), L8(70.80,±20%), L9(1.00,±50%), L10(1.00,±50%), L11(5.00,±10%), L12(4.00,±25%), L13(3.00,±25%), T1(2.00,±50%), T2(2.00,±50%). The size of the outlet opening was designed with a value A=14cm. However, the deformation A±2δ inevitably involves the following changes in other relevant radial dimensions: φ2, φ3, and φ4 change by ±2δ (similar to A), and R1 and R2 change by half of A (±δ). In this way, the inlet opening (1) for the beam is deformable according to the directional requirements of the target (2). The design in Figure 1 is also shown in Figure 2 in three dimensions. It should be noted that the device is symmetric with respect to the axis.

[0045] The verification of the preferred embodiments shown in Figures 1 and 2 was carried out by comparing the quality parameters imposed by the IAEA with the quality parameters obtained in the above design. First, for proton beams at 2.0 and 2.1 MeV, DPMC was verified by Monte Carlo simulation for two types of models (a cylindrical model filled with ICRU-4 standard microstructure, and the other being a Snyder model).

[0046] The results of each simulation for each model are summarized in Table 1. [Table 1]

[0047] Total equivalent radiation dose (D) in units of equivalent gray (Gy-Eq) T The following formula was used to estimate ). D T =(w│ │th+χr·w B )D th + w fast ·D fast +D However, D th is the thermal neutron dose, r=0.422, χ represents the concentration of boron applied to the treatment (its value is approximately 35 in tumor tissue and 10 in healthy tissue), w th , w fast and w B These are a set of weighting parameters that depend on the ratio of biological effectiveness (RBE) of contributions from thermal neutrons, fast neutrons, and boron, respectively. In particular, w th and w fast This is equal to 3.2 for both tumor tissue and healthy tissue. In contrast, the weighting of boron is equal to 3.2 for healthy tissue (w B Compared to (=1.3), tumors have a higher (w B =3.8).

[0048] Secondly, Table 2 compares various quality parameters of the neutron beam obtained from the DPMC based on IAEA recommendations. In particular, the results for proton beams at 2.0 and 2.1 MeV are shown, respectively. The energy epithermal limits (LEs) were set to 10 and 20 keV. It should be noted that approximately half of the dose produced by fast neutrons corresponds to neutrons with energies in the range of 10 to 20 keV. Furthermore, while the proposed invention satisfied all IAEA recommendations when the incident proton beam had an energy of 2.1 MeV, it fell short in terms of epithermal flux at 2.0 MeV. Another aspect to note is that, as a result of a preferred embodiment of the proposed invention, the IAEA requirements can be satisfied by considering only epithermal neutrons in the range of 0.5 eV to 10 keV, which are most suitable for BNCT treatment. This is achieved as a result of the filtration stage (5) and shield (7) and the materials forming them.

[0049] Thirdly, the neutron spectrum in the DPMC was analyzed. In particular, Figure 3 shows the neutron spectra at various locations within the DPMC and its exit aperture (6), reflecting deceleration and subsequent filtration of undesirable neutrons. The material selection in this design minimizes thermal and fast electron flux without reducing the epithermal flux. Of particular interest is the deceleration of the highest-energy neutrons within the MgF2 layer, which allows the spectral maximum to be achieved at 2-3 keV, optimal for BNCT therapy (especially for deep tumors).

[0050] [Table 2]

[0051] In addition, this was compared with spectra provided by other DPMC facilities (particularly Fir-1 and C-BENS). The results are shown in Figure 4 (logarithmic scale) and Figure 5 (linear scale).

[0052] Figure 6 shows the lateral profiles of the radial neutron flux (epithermal, thermal, and fast) and gamma-ray emission at the exit aperture (6) on a logarithmic scale. The good beam demarcation at the exit aperture (6) and the efficient suppression of neutrons outside the exit aperture (6), demarcated by the vertical dashed line in the central region of the graph, are remarkable. In particular, the epithermal neutron flux decreases by two orders of magnitude in the first 15 cm, while the attenuation of thermal neutrons is much more pronounced, occurring in the first 5 cm. In addition, the gamma-ray emission is well attenuated throughout the entire emission region. This avoids contamination of the resulting neutron beam with respect to both gamma-ray emission and off-axis contributions.

[0053] In some preferred embodiments of the present invention, the reflective cover (4) comprises at least one of the following materials: Ni, Pb, BeO, Bi. In the case of beryllium oxide, the usable isotopes are 9 It is Be. This has a high elastic cross-sectional area, which accounts for almost the entire cross-sectional area up to the MeV range, and in that case the absorption loss is minimized. However, this has two drawbacks (both 9 This has the characteristic (due to the low mass of Be). On the one hand, neutron collisions do not occur mainly at large angles (backward reflection), and therefore many neutrons reach the outside of the DPMC along their paths, diffusing slightly but not being reflected, which requires a greater thickness of material. On the other hand, due to the dynamics of elastic collisions, neutrons lose far more energy compared to heavier nuclei, so neutrons are excessively decelerated. Therefore, BeO may be more suitable when using higher initial energies for neutrons, exceeding 2-2.1 MeV, as used in embodiments of the present invention. In such cases, it would contribute to deceleration together with MgF2 as a result of its intermediate behavior between reflector and moderator.

Claims

1. A device for generating, slowing down, and composing a neutron beam, based on the generation of neutrons from a proton beam, - The entrance opening (1) from which the proton beam is directed, - A target (2) positioned within the path of the proton beam to generate a neutron beam that interacts with the proton beam to define the main axis of propagation, - A cooling module for cooling the target (2), - A moderator (3) that contacts the target (2), having a thickness (W2) between 19.62 cm and 23.98 cm in the direction of the proton beam from the target (2) to the filtration stage (5), and slowing down the neutrons produced by the nuclear interaction to an energy in the epithermal range, - A reflective cover (4) surrounding the moderator (3), which redirects the diffused neutrons toward the main axis and increases the epithermal neutron flux, - The exit aperture (6) from which the neutron beam is emitted, - In order to suppress neutron and gamma-ray radiation that does not exit the device through the exit opening (6), a shield (7) is arranged around the exit opening (6), - A filtration stage (5) for filtering the neutron beam before it exits the device through the outlet opening (6), wherein the filtration stage (5) is in contact with the outlet opening (6) and surrounded by the reflective cover (4), and the filtration stage (5) comprises at least three layers, namely a fast neutron filtration layer, a thermal neutron filtration layer and a gamma-ray emission filtration layer, Equipped with, The aforementioned high-speed neutron filtration layer contains Al, The thermal neutron filtration layer contains LiF, The gamma-ray emission filtration layer includes at least one of Pb and Bi. device.

2. The device according to claim 1, wherein the high-speed neutron filtration layer is made of Al.

3. The device according to claim 1, wherein the thermal neutron filtration layer is made of LiF.

4. The device according to claim 1, wherein the total thickness of the moderator (L4 + L5) is between 24.64 cm and 36.96 cm, and covers the target and a portion of the accelerator tube up to the inlet opening.

5. The aforementioned speed reducer (3) is made of the following material: graphite, D ２ O, AlF ３ CaF ２ Li ２ CO ３ MgF ２ Al ２ O ３ The device according to claim 4, manufactured from at least one of the following: or a combination thereof.

6. The moderator (3) is MgF ２ manufactured according to claim 5.

7. The high-speed neutron filtration layer included in the filtration stage has a thickness of 1.00 cm ± 15% (L1). A device for generating, slowing, and structuring a neutron beam according to any one of claims 1 to 6.

8. The thermal neutron filtration layer included in the filtration stage (5) has a thickness of 0.20 cm ± 20% (L2), A device for generating, slowing down, and structuring a neutron beam according to any one of claims 1 to 7.

9. The gamma-ray emission filtration layer included in the filtration stage (5) has a thickness of 1.00 cm ± 15% (L3), A device for generating, slowing, and structuring a neutron beam according to any one of claims 1 to 8.

10. The device according to claim 1, characterized in that the gamma-ray emission filtration layer is made of Bi.

11. The device according to any one of claims 7 to 10, wherein the thermal neutron filtration layer and the gamma-ray emission filtration layer are arranged such that the thermal neutron filtration layer is first positioned along the direction of flight of the generated neutron beam, and then the gamma-ray emission filtration layer is positioned.

12. The device according to claim 11, wherein the fast neutron filtration layer, the thermal neutron filtration layer, and the gamma-ray emission filtration layer are arranged in this order along the direction of flight of the generated neutron beam.

13. The reflective cover (4) surrounding the moderator (3), which redirects the diffused neutrons towards the main axis, has a thickness (L6) of 25.00 cm ± 40% in the direction of the proton beam from the moderator to the inlet opening. A device for generating, slowing, and structuring a neutron beam according to any one of claims 1 to 12.

14. The device according to any one of claims 1 to 13, wherein the reflective cover (4) comprises at least one of the following materials: Ni, Pb, BeO, or Bi.

15. The device according to claim 14, wherein the reflective cover (4) is made of Pb.

16. It has an outlet opening with a diameter of A ± 2δ, and the radial dimensions are as follows: - Rear diameter of the reduction gear (φ2): A ± 2δ + 36 cm ± 10% - Diameter (φ3) of the cover (4): A ± 2δ + 106 cm ± 15% - Diameter of the device (φ4): A ± 2δ + 116 cm ± 20% - Inner diameter (R1) of the collimator of shield (7): (0.5A ± δ + 3cm ± 10%) - Outer diameter (R2) of the collimator of the shield (7): (0.5A ± δ + 22.5 cm ± 50%) A device according to any one of claims 1 to 15, having the following features.

17. The aforementioned target (2) is ７ The nuclear interaction with the incident proton beam, which contains Li, is ７ Li(p,n) ７ The device according to any one of claims 1 to 16, wherein Be.

18. The device according to any one of claims 1 to 17, wherein the exit aperture (6) for the neutron beam has at least one portion of one of the following geometric shapes: cylindrical, conical, pyramidal, or truncated pyramidal.

19. The device according to any one of claims 1 to 18, wherein the exit aperture (6) for the neutron beam is provided with a movable closure for stopping irradiation.

20. The shield (7) positioned around the exit opening (6) for the neutron beam is made of the following material: LiF, ６ LiF, B ４ The device according to any one of claims 1 to 19, comprising at least one of C, polyethylene, Pb, and Bi.

21. A device according to any one of claims 1 to 20 for use in boron neutron capture therapy.

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