High-intensity multi-particle cyclotron for industrial production of α and β radionuclides

Abstract

The invention relates to a cyclotron which enables the production of α- or β-emitting radionuclides. The cyclotron, with a magnetic periodicity of 3, comprises three accelerating cavities connected to the centre, thus not requiring phase control between the cavities, forming a single high-frequency resonator. The six accelerating gaps per turn enable rapid acceleration (the angle ϕ between the accelerating gaps of each cavity being approximately 30°) which is essential for acceleration at the third and sixth harmonics. This cyclotron preferably has an injection system (31) supplied by different types of ion sources, making it possible to efficiently accelerate charged particles having Z / A ratios equal to 1 / 2 and to 1 / 4. The cyclotron may also have stripping extraction means positioned in the cyclotron so as to extract the charged particles and double their state of charge. These particles enable a set of nuclear reactions for producing α-emitting radionuclides.

Description

[0001] HIGH-INTENSITY MULTI-PARTICULAR CYCLOTRON FOR THE INDUSTRIAL PRODUCTION OF RADIONUCLIDES and

[0002] TECHNICAL FIELD

[0003] This application relates to the technical field of cyclotrons and more particularly those intended for the production of radionuclides such as can be implemented in targeted therapy in oncology.

[0004] STATE OF THE ART

[0005] The rapid development of personalized medicine relies on "theranostics," a neologism that combines therapy and diagnosis. This type of targeted therapy uses alpha and p-emitting radionuclides.

[0006] Examples of alpha emitters include Astate-211 (noted At-211 or 211 At), Terbium-149 (noted Tb-149 or 149 Tb) or Actinium-225 (noted Ac-225 or 225 Ac). Examples of p- emitters include Lutetium-177 (denoted Lu-177 or 177 Lu), Terbium-161 (noted Tb-161 or161 Tb) or Holmium-166 (noted Ho-166 or 166 Ho).

[0007] p-emitters are generally produced by neutron capture in specific nuclear reactors. However, this method of producing p-emitters can pose logistical problems for supplying nuclear medicine centers.

[0008] It is known that alpha emitters can be obtained using cyclotron-type particle accelerators, notably by ion bombardment. 4 Hey 2+ , H + , Or 12 C 6+ on specific targets. The p- emitters are obtained by bombarding them with intense beams of H ions + or D +(protons and deuterons) at high energies (in the 40 to 20 MeV range) producing nuclear reactions on specific targets. The production of the various p- emitters can also be achieved by a method called "ARC" for "Adiabatic Resonance Crossing". This method is detailed in the document "Resonance Enhanced Neutron Captures for Element Activation and Waste Transmutation", C. Rubbia, CERN-LHC-97-04-EET, June 1997.

[0009] These methods have the advantage of being able to be implemented in a facility close to nuclear medicine centers. However, they require the prior production of different types of charged particles, which are then accelerated (for example, using a cyclotron).

[0010] A facility for producing emitters of different types generally includes a cyclotron and beamlines feeding specific production targets for alpha-emitting radionuclides or p-emitting radionuclides. SUMMARY

[0011] To resolve, at least partially, the aforementioned technical problems, the invention provides for an isochron cyclotron configured to accelerate charged particles having a charge state Z and a number of nucleons A and whose ratio Z / A is equal to 1 / 4 or equal to 1 / 2, the cyclotron being remarkable in that it comprises a radio frequency accelerating system, of periodicity three, comprising, and preferably being composed of, three electrodes, called "dice" (or "acceleration electrodes" or "accelerating electrodes"), intended to be connected to an oscillating radio frequency electrical voltage, and three other electrodes, called "anti-dice" (or "complementary electrodes"), intended to be connected to the electrical ground.

[0012] The anti-dice, together with the three dice, form six spaces, called accelerating spaces, within which the charged particles are intended to be accelerated, the accelerating spaces each having a proximal portion extending from a neighborhood of a cyclotron center and a distal portion extending from the proximal portion and substantially in a main radial direction, the three dice are electrically connected to each other in the vicinity of the cyclotron center so as to form a single radiofrequency cavity, and for each die, the main directions of two adjacent accelerating spaces form an angle, called the "opening angle", between 25° and 40°.

[0013] Connecting the accelerating electrodes to the center of the cyclotron creates a radiofrequency resonant cavity in which an electric field wave can propagate. Whereas accelerating electrodes are usually connected to different electric field generators, the simplification provided by the central connection allows all accelerating electrodes to be excited using only a single electric field generator. Furthermore, it is no longer necessary to regulate the phases between the different accelerating electrodes. This feature allows for more efficient acceleration of charged particles, particularly when the acceleration is performed at the 6th harmonic of the particles' rotation frequency (usually difficult to use due to phase fluctuations between the electrodes).

[0014] The opening angle between the accelerating spaces allows for the efficient acceleration of particles with: a Z / A ratio equal to 1 / 2, thanks to a 3rd harmonic; and a Z / A ratio equal to 1 / 4, thanks to a 6th harmonic.

[0015] Thus, thanks to its unique cavity and specific opening angle, the cyclotron according to the invention offers a sufficiently favorable compromise for accelerating particles with different Z / A ratios while maintaining high intensity. This allows a single cyclotron to be used across multiple production lines. Each production line aims, for example, to produce alpha emitters or p- emitters. Generally, each production line includes an ion source and a cyclotron to accelerate the charged particles. The installation of such facilities is therefore substantial. The cyclotron according to the invention can be shared between different production lines, directly reducing the footprint of alpha and / or p- emitter production facilities.

[0016] The invention also relates to a method for producing alpha and beta-emitting radionuclides, preferably for medical use, comprising the following steps carried out using a cyclotron according to the invention; injecting a beam of charged particles having a Z / A ratio of 1 / 4 or 1 / 2 into the plane of symmetry of the cyclotron; directing the beam of accelerated charged particles towards at least one target.

[0017] The invention further relates to a method for producing a deuteron ion beam from molecular deuterium ions having a charge state Z, a nucleon number A, and a Z / A ratio of 1 / 4. The method is implemented using a cyclotron as described above or, alternatively, another cyclotron. In particular, this other cyclotron may not include a radiofrequency accelerator system with a periodicity of three, nor an aperture angle between 25° and 40°. The cyclotron does, however, include an extraction means configured to increase the Z / A ratio of the molecular deuterium ions when they interact with it.

[0018] The process may be subject to independent protection.

[0019] The production process includes, for example, the following steps: accelerating molecular deuterium ions; causing an interaction of said accelerated molecular deuterium ions with the extraction means so as to dissociate each molecular deuterium ion into deuteron ions in order to form said deuteron ion bundle.

[0020] The process involves molecular deuterium ions, which have a Z / A ratio of 1 / 4, using only one electron to form the molecular bond between the two deuteron nuclei. Thus, the interaction with the extraction medium, as provided by the process, removes this bonding electron, resulting in the dissociation of the molecule into two deuteron ions. It is easier to efficiently produce and accelerate ions with a low Z / A ratio (e.g., 1 / 4) to subsequently increase their charge state. Therefore, the process allows the efficient production of ions with a Z / A ratio of 1 / 2 for use, for example, in the production of p- radionuclides. BRIEF DESCRIPTION OF FIGURES

[0021] The aims, objects, features and advantages of the invention will become clearer from the detailed description of an embodiment thereof, which is illustrated by the following accompanying drawings in which:

[0022] Figures 1A and 1B represent 3-dimensional views of the magnet.

[0023] Figure 2 represents an example of an accelerator system such as can be implemented in a cyclotron according to the invention.

[0024] Figure 3 shows a magnification of the accelerating system of Figure 2.

[0025] Figures 4A and 4B schematically represent the accelerating system of Figure 2 and an example of a trajectory that can be followed by ions during their acceleration by the cyclotron.

[0026] Figure 5 represents an embodiment of the cyclotron according to the invention and an example of a trajectory that can be followed by an ion accelerated and extracted from the cyclotron.

[0027] Figure 6 shows an example of an injection line comprising three ion sources.

[0028] The drawings are provided by way of example and are not intended to limit the scope of the invention. They are schematic representations of the principle intended to facilitate understanding of the invention and are not necessarily to scale with practical applications. In particular, Figures 2 to 6 are not representative of reality.

[0029] DETAILED DESCRIPTION

[0030] Before beginning a detailed review of embodiments of the invention, optional features that may possibly be used in association or alternatively are stated below.

[0031] Advantageously, the cyclotron includes a high-frequency voltage source configured to apply a radio-frequency oscillating electrical voltage to each die, the frequency of the radio-frequency oscillating electrical voltage being chosen such that said frequency is a harmonic of a rotational frequency of the charged particles in the cyclotron. The frequency of the radio-frequency oscillating electrical voltage is preferably also dependent on the Z / A ratio of the charged particles.

[0032] Advantageously, the opening angle is between 25° and 35°.

[0033] Preferably, the opening angle is between 28° and 32° and ideally 30°.

[0034] In one embodiment, the cyclotron includes a magnetic field exhibiting azimuthal modulation, invariant over a periodicity of three.

[0035] In one embodiment, the cyclotron includes a voltage source, referred to as "high frequency", configured to apply an electric field to each die (41), said electric field having a frequency HF such as : where B is the magnetic field induction, U o is a unified atomic mass unit of charged particles intended to be accelerated by the cyclotron, c is the speed of light in a vacuum, and h is a harmonic of a frequency cyc of revolution of the charged particles in the cyclotron, said frequency cyc of revolution exhibiting at least two harmonics h0 and h ± such that hZ / A is constant for h = h0 and IA = 1 / 2 and for h = h ± and ZI A = 1 / 4.

[0036] In a cyclotron development, h0 = 3 and h ± = 6.

[0037] In one variant, the cyclotron includes a line for injecting charged particles into a plane of symmetry of the cyclotron, the line of injection being disposed in an axis of the cyclotron, said axis of the cyclotron being an axis around which the magnetic field, and preferably the modulation of the magnetic field, exhibits rotational invariance of order three.

[0038] In one development, the cyclotron includes at least two charged particle sources, one of the sources being configured to produce charged particles having a Z / A ratio of 1 / 2 and another of the sources being configured to produce charged particles having a Z / A ratio of 1 / 4, the at least two sources being mounted on the injection line so as to permit the injection of the charged particles produced into the plane of symmetry of the cyclotron.

[0039] In one embodiment of the cyclotron, the three accelerating electrodes are galvanically connected.

[0040] The use of a cyclotron requires the prior production of various types of charged particles in ion sources that produce intense beams. These high-performance sources are external, and specific devices inject the ions into the cyclotron for acceleration. The production of such ions can be carried out in different types of sources.

[0041] For example, the production of ions 4 Hey 2+ or 12 C 6+ can be carried out in cyclotron resonance sources (known as "ECR sources") in which a plasma allows the complete ionization of different elements, such as 4 He and 12C. The efficiency of these ECR sources decreases as the expected state of charge increases. By "state of charge," we mean the degree of ionization, that is, the number of electrons that the neutral atom has lost during collisions in the plasma. An ECR source is, for example, much more efficient at producing ions 12 C 3+ than ions 12 C 6+ For example, an ECR source can produce 300 mA of electrical current (emA). 12 C 3+ , to be compared with 30 emA for the 12 C 6+ , completely ionized. The number of ions in a high charge state (for example 12 C 6+The number of alpha emitters that can be produced is therefore low. Consequently, the number of alpha emitters that can be produced from these ions is small. Currently, this production method cannot meet the growing demand from nuclear medicine centers. There is therefore a need to increase alpha emitter production by improving the performance of cyclotrons and for cyclotron-controlled p-emitter production, i.e., without requiring implementation in a nuclear reactor.

[0042] There is therefore a need to increase the production of alpha and / or p- emitters (the latter are currently produced in nuclear reactors).

[0043] To this end, in one embodiment, the cyclotron includes at least one extraction means configured to increase the Z / A ratio of the charged particles when they interact with said extraction means, preferably at high energy, each extraction means being disposed in the cyclotron to intersect a trajectory of the charged particles when they are accelerated by said cyclotron, each extraction means being disposed at a local minimum of the azimuthal modulation of the magnetic field.

[0044] Increasing the charge state by stripping charged particles reduces the radius of curvature of their trajectory in the midplane. They then follow a re-entrant trajectory towards the center of the cyclotron. Indeed, after interacting with the stripper, which is the extraction method, the particles pass through a region (called the "hill") where the magnetic field is stronger, immediately adjacent to the region (called the "valley") where the magnetic field is weaker and where the extraction method is located. The associated increase in the magnetic field increases the Laplace force exerted on the particles, thus reducing the radius of curvature of their trajectory. The charged particles then complete a half-turn inside the cyclotron to reach the magnetic valley again, where the Laplace force is weaker. The radius of curvature of the particles' trajectory increases.The trajectory of the particles straightens and they then head towards the edge of the pole of the cyclotron magnet from where they can be extracted.

[0045] The extraction method thus makes it possible to extract charged particles from the cyclotron without using a specific extraction channel.

[0046] The extraction method also has the advantage of increasing the charge state of the particles once they have been accelerated. The particles exiting the cyclotron then exhibit a high charge state, which can be similar to the charge states of particles accelerated in a conventional cyclotron.

[0047] Therefore, it is not necessary to inject particles that already have a high charge state. Particles with a low charge state, such as 4 Hey + , 12 C 3+ Or 2 H2 +can be used. Since it is more efficient to produce particles with a low charge state, it is possible to inject a higher current into the cyclotron. The flux of particles extracted from the cyclotron per second according to the invention is therefore greater: this cyclotron thus produces high-intensity beams.

[0048] Increasing the Z / A ratio, for example, corresponds to doubling that ratio.

[0049] In one embodiment, the cyclotron includes a plurality of extraction means configured to increase the Z / A ratio of the ions to be accelerated when they interact with the high-energy extraction means, each extraction means intersecting the median plane at a local minimum of the azimuthal amplitude modulation of the magnetic field.

[0050] In one embodiment of the cyclotron, the average magnetic field induction (B) is between 3 T and 3.5 T.

[0051] In one embodiment, the cyclotron includes a superconducting coil configured to generate a magnetic field induction compatible with a molecular hydrogen dissociation rate of less than 2 x 10 -3 .

[0052] In one embodiment, the process preferably includes, simultaneously with the injection of the charged particle beam, the application of a radio-frequency oscillating electrical voltage to the cyclotron dice to accelerate the injected charged particles. In another embodiment of the process, the charged particle beam, having a Z / A ratio of 1 / 4, comprises 4 Hey + and / or of the 12 C 3+ and / or D2 + , and the beam of charged particles having a Z / A ratio equal to 1 / 2 includes FV.

[0053] In one implementation, the deuteron ion beam production process is configured to accelerate molecular deuterium ions to an energy greater than or equal to 16 MeV (i.e., an energy greater than or equal to 4 MeV / nucleon) and preferably greater than or equal to 32 MeV (i.e., an energy greater than or equal to 8 MeV / nucleon). Thus, each deuteron ion produced will have an energy of at least 8 MeV (i.e., 4 MeV / nucleon), or even at least 16 MeV.

[0054] In one embodiment of the process for producing a deuteron ion beam, the cyclotron includes a magnetic field with an azimuthal variation designed to create sectors of weak magnetic field; and the interaction of said accelerated molecular deuterium ions with the extraction means is carried out in one of these sectors of weak magnetic field. Thus, reducing the radius of curvature of the deuteron ion trajectory allows the deuteron ions to be extracted from the cyclotron without the need for a supplementary extraction device.

[0055] By "isochronous acceleration" we mean acceleration by means of an alternating electric field at a constant frequency.

[0056] By "invariant with respect to a periodicity of three", we mean, for example, invariant with respect to a rotation of order three.

[0057] By "object having a periodicity of three", we mean an object whose shape exhibits invariance under rotation of order three.

[0058] By "radio frequency oscillating electrical voltage", we mean an electrical voltage varying over time at a frequency greater than 10 MHz and preferably between 30 MHz and 150 MHz, for example equal to 70 MHz.

[0059] By "static magnetic field" we mean a magnetic field that does not vary over time.

[0060] By "high energy," we mean energies beyond the threshold of the nuclear reactions that produce the specific radionuclides under consideration. This includes, for example, 4 MeV / nucleons, or 8 MeV / nucleons or even more.

[0061] By "high frequency" we mean a frequency greater than 10 MHz and preferably between 30 MHz and 150 MHz, for example equal to 70 MHz.

[0062] By "charge-to-mass ratio of a charged particle", we mean the quotient of a number of elementary electric charges divided by the number of nucleons of the charged particle.

[0063] By "increasing the charge-to-mass ratio of a charged particle", we mean increasing an absolute value of the charge-to-mass ratio.

[0064] The term "unified atomic mass unit" refers to 931.494 MeV / c². 2 .

[0065] Figures 1A and 1B show a first embodiment of a cyclotron 1 according to the invention in two views. The cyclotron 1 is configured to accelerate charged particles to high energies. These particles can be light or heavy ions, or partially ionized molecules (such as molecular dihydrogen FV). These charged particles are accelerated along trajectories F which have, at least in part, a spiral shape extending along a plane 3 called the "median plane".

[0066] Cyclotron 1 is special in that it can operate in an "isochronous" regime. The term isochronous refers to a specific condition in which the cyclotron frequency of the charged particles is kept constant during particle acceleration, despite the increase in their energy and relativistic mass (the frequency at which the charged particles spiral in the cyclotron is normally proportional to the charge of the particle and the intensity of the magnetic field in which the particles are immersed, and is inversely proportional to the mass of the particles).

[0067] To maintain isochronism as the speed of charged particles increases, one solution is to modulate the magnetic field in which the charged particles are immersed. The modulation of the magnetic field is azimuthal. This is why isochronous cyclotrons can also be called "AVF" cyclotrons, for "Azimuthal Varying Field." The azimuthal variation of the magnetic field can be achieved, for example, by alternating sectors of strong and weak magnetic fields.

[0068] Figure 1A shows an embodiment of the cyclotron 1 in perspective and open view, in which said cyclotron 1 includes a magnetic field source (partially shown). This is, for example, an electromagnet 21. This electromagnet 21 includes, for example, a conducting or superconducting coil enclosing a core made of ferromagnetic or paramagnetic material. In the illustrated example, the core is structured to form sectors 221, 222, allowing a modulated magnetic field to be applied in a plane 3 of the cyclotron 1, referred to as the "median" plane. Only one part of the magnetic field source is shown, the other part being removed. In Figure 1B, the two parts 22 of the magnetic field source are shown assembled one on top of the other.

[0069] The median plane 3 is preferably a plane of symmetry of the magnetic field source. Thus, the vertical component Bz of the magnetic field B is most intense in the vicinity of the median plane 3. An average value of this component Bz is, for example, between 1 T and 4 T, and preferably between 3 T and 3.5 T. The magnetic field source includes, for example, a superconducting coil configured to generate a magnetic field induction (B) compatible with a molecular hydrogen dissociation rate of less than 2 × 10⁻¹¹. -3 This reduces high-intensity beam losses to an acceptable level at high energy.

[0070] The azimuthal modulation of the magnetic field is special in that it is of the third order. In other words, the azimuthal modulation exhibits rotational invariance through an angle of 2n / n about an axis where n, called the "order of symmetry" (or simply "order"), is an integer equal to three. The axis of rotation is normal to the median plane 3 and is called the "axis of rotational symmetry." This rotational invariance of the third order is obtained, for example, through the arrangement of sectors 221, 222 of the magnetic field source. The first three sectors 221 (called "hills") correspond to the strong field and are arranged in a circular pattern, extending radially from a center 30 of the median plane 3. The hills form angles of 120° with each other. Three other sectors 222 (called "valleys") correspond to the weak field and are arranged between the hills 221.

[0071] The median plane 3 includes a center 30 in the vicinity of which charged particles destined for acceleration are injected (the particles are then said to be "low energy"). The median plane 3 also includes an edge which corresponds, for example, to a physical boundary of the cyclotron 1 such as an edge of the magnet.

[0072] Cyclotron 1, as shown in Figures 1A and 2, includes a resonant cavity 40, also called an RF cavity (for "Radio Frequency," these types of cavities are generally tuned to frequencies between 10 MHz and 150 MHz). The RF cavity 40 is configured to apply a high-frequency electric field to the median plane 3. For this purpose, the median plane 3 is preferably a plane of symmetry of the RF cavity 40.

[0073] The resonant aspect of the RF 40 cavity allows the high-frequency electric field to be amplified when it is close to the resonance frequency of cavity 40. The acceleration of charged particles in cyclotron 1 is thereby improved.

[0074] Using a single RF cavity offers a significant advantage by eliminating the need for electric field phase control. Prior art cyclotrons typically comprise several separate RF cavities, each requiring phase control. Poor phase control inevitably reduces the efficiency of charged particle acceleration, consequently decreasing the intensity of the accelerated particle flux. Precise phase control of RF cavities is particularly important when the harmonics used for particle acceleration are high. Accelerating particles using the 6th harmonic (h = 6) is challenging, especially when the number of revolutions required by the particles is high.Thus, the use of a single RF cavity 40 allows for the regulation of the electric field phase throughout the cavity without requiring precise control. The single RF cavity therefore enables efficient acceleration on the 6th harmonic.

[0075] The RF cavity 40 is unique in that it is formed by three conducting electrodes 41, also called "accelerating electrodes" or "dee." The accelerating electrodes 41 extend preferentially parallel to, across, or partially within the median plane 3. The electrodes 41 are configured to apply an electric field in the region of the median plane 3, and specifically to charged particles, in order to accelerate them.

[0076] In the absence of an electrical connection between the electrodes 41, each accelerating electrode 41 can form an independent radio frequency resonant cavity, with all the cavities formed being independent of each other. To form the single RF cavity 40, the accelerating electrodes 41 are electrically connected to each other. For example, they are galvanically connected. The electrodes 41 can be electrically connected by means of transmission lines. However, the topology of the RF cavity 40 is more complex, and the sizing of the transmission lines must be taken into account to adjust the cavity resonance. To overcome this drawback, the electrodes 41 are preferably electrically connected to each other in the vicinity of the center 30 of the median plane 3. Ideally, the electrodes 41 extend towards the center 30 until they meet and form the electrical and, preferably, mechanical connection.The neighborhood is preferably determined from the projection of the electrodes 41 onto the median plane 3. The neighborhood preferably corresponds to an area extending within 15 cm of the center 30 of the median plane 3, for example, within 10 cm of the center 30 of the median plane 3. Thanks to the electrical connection made near the center 30, the resulting RF cavity 40 maintains a simple topology. The propagation of the electric field in the cavity 40 can be easily calculated. It is not necessary to consider the length and impedance of the transmission line. The cyclotron (1) also includes three complementary conducting electrodes 42, called "anti-dee" electrodes. These electrodes 42 are connected to ground so that a potential difference applied between the accelerating electrodes 41 and the complementary electrodes 42 creates an electric field.For this purpose, each of the accelerating electrodes 41 is electrically isolated from the complementary electrodes 42.

[0077] The accelerating electrodes 41 and complementary electrodes 42 are arranged to allow an electric field to be applied at the level of the median plane 3 and preferably parallel to the median plane 3. Thus, this electric field allows the charged particles moving in the median plane 3 to be accelerated.

[0078] The electrodes 41 and the complementary electrodes 42 (or respectively dice and anti-dice) can have different shapes to allow the application of an electric field in the median plane 3. For example, they can be partially curved to form U-shapes. In this case, they are positioned symmetrically with respect to the median plane 3. They can also extend at least partially into the median plane 3 and intersect it. In this variant, openings 410, 420 are made in the accelerating electrodes 41 and / or the complementary electrodes 42 to allow the passage of charged particles moving in the median plane 3. Figure 3 shows an example of an opening 410, 420 made in a portion of the electrodes and complementary electrodes 41, 42.The position of the openings 410, 420 is adjusted so that the particles can be accelerated along circular trajectories by part without encountering obstacles.

[0079] The accelerating electrodes 41 and complementary electrodes 42 are arranged alternately in a circular pattern. Each accelerating electrode 41 is positioned between two adjacent complementary electrodes 42. Thus, each accelerating electrode 41, together with its adjacent complementary electrodes 42, forms first and second GE, GS gaps, also called accelerating gaps. The cyclotron 1 is configured so that charged particles are accelerated within these GE, GS gaps. Specifically, the GE, GS gaps are empty spaces between the accelerating electrodes 41 and the complementary electrodes 42, within which the electric field is established to accelerate the charged particles. Each GE, GS gap has, at least partially, a substantially radial orientation.By "radial orientation," we mean an orientation aligned along a ray passing through the center 30 of the median plane 3. By "approximately radial," we mean oriented parallel to the ray passing through the center 30 of the median plane 3, to within + / - 20°, or even + / - 10°. This approximately radial orientation can vary along each accelerating space GE, GS. We will consider that the approximately radial orientation is verified for any part of the accelerating spaces GE, GS extending more than 15 cm, and preferably 25 cm, from the center 30 of the median plane 3.

[0080] One of the GE accelerating gaps can be called the "entry gap" when the charged particle enters the RF cavity formed by an accelerating electrode 41 (in other words, when the particle passes from a complementary electrode 42 to an accelerating electrode 41). The other of the GS accelerating gaps can be called the "exit gap" when the charged particle exits the RF cavity (in other words, when the particle passes from an accelerating electrode 41 to a complementary electrode 42).

[0081] The unique RF cavity 40 also includes a high-frequency electric field source (with a frequency greater than 30 MHz), configured to apply an electric field to one of the accelerating electrodes 41. This field source includes, for example, a wave generator coupled to one of the accelerating electrodes 41 by means of a coupling loop 44. The electric field source may also include a tuning piston 45 for fine-tuning the desired field frequency. The electric field then propagates within the RF cavity 40 without the need for phase control between different generators.

[0082] Figure 5 shows, for example, that the central space of the electromagnet 21 is structured to form, for example, three hills 221 in the shape of a "T" and arranged according to a rotation of 120° around the center 30 of the median plane 3.

[0083] Figures 4A and 4B schematically represent trajectories F that can be followed by charged particles accelerated by the cyclotron 1 according to the invention. In the illustrated examples, only about two revolutions are shown. In the case of Figure 4A, these are charged particles (ions or ionized molecules) having a number of elementary charges Z (also called the "state of charge") and a number of nucleons A (total, particularly in the case of ionized molecules) such that Z / A = 1 / 4. These are, for example, particles of 4 Hey + Or 12 C 3+ In the case of Figure 4B, these are particles with a Z / A ratio of 1 / 2. For example, H2 + OR of Ü2 + (D) meaning deuterium - also noted 2H). Cyclotron 1 is remarkable in that it allows the efficient acceleration of both particles with a Z / A = 1 / 4 and particles with a Z / A = 1 / 2, without changing accelerating system 4.

[0084] An example implementation allows the acceleration of ions with a Z / A ratio equal to 1 / 4 (for example, molecular ions Ü2 + ions 4 Hey + And 12 C 3+ A positive ion 4 Hey + is a helium atom that has lost a single electron. In this case, Z = 1. The ion 4 Hey + comprises 4 nucleons (A = 4). The electric charge-to-mass ratio, which we will denote in the rest of the description as Z / A, is therefore equal to 1 / 4 in the case of the ion 4 Hey + It is also possible to consider the ion 12 C 3+ (where Z / A = 1 / 4). A molecular ion FV comprises two protons and one electron. The equivalent Z / A ratio is 1 / 2.

[0085] Since the number of accelerating electrodes 41 is three, the particles can be accelerated by means of electric field harmonics that are multiples of three. For example, particles with a Z / A ratio of 1 / 2 are accelerated by the third harmonic of the particle frequency (harmonic of rank h = 3). Particles twice as heavy, with a Z / A ratio of 1 / 4, are accelerated by the sixth harmonic (h = 6) of the particle frequency.

[0086] In Figures 4A and 4B, the accelerating spaces GE, GS are represented by straight rays extending from the center 30 of the median plane 3. This is an approximation, but it proves correct for at least some of the spaces GE, GS (or at least correct at a distance from the center 30 of the median plane greater than 15 cm). Each accelerating space GE, GS, for example, has two portions: a GEP portion, called the "proximal" portion, and a GSP portion, called the "distal" portion. The opening angle corresponds to the angle formed between consecutive accelerating spaces GE, GS, that is, those located on either side of the same accelerating electrode 41.

[0087] The distal portions GED, GSD of the accelerating spaces GE, GS are considered preferentially. The distal portion of each accelerating space GE, GS is preferably linear. Alternatively, it may be non-linear, as shown in Figure 3. In this case, the principal direction is defined, for the distal portion of each accelerating space GE, GS, by a straight, radial direction passing through the center 30 of cyclotron 1 and which is as close as possible to a median curve of the distal portion of said accelerating space GE, GS. The median curve is a curve that lies equidistant from the edges of the accelerating space GE, GS and, in particular, from its distal portion GED, GSD.

[0088] Whether the distal portion GED, GSD of each accelerating space GE, GS is linear or not, the opening angle is then defined as the angle formed by the straight, radial directions passing through the center 30 of the cyclotron 1 for each of the consecutive accelerating spaces GE, GS, that is to say arranged on either side of the same accelerating electrode 41.

[0089] The maximum amplitude of the electric field is symbolized in Figures 4A and 4B by peaks 46 on the trajectories F. The minimum amplitude of the electric field (allowing maximum energy gain during passage through GS) is symbolized by troughs 47 on the trajectories F. The particles are efficiently accelerated during their passage through the GE and GS spaces, particularly when the distance between these GE and GS spaces corresponds to the flight time of the charged particle on the trajectory F. Thus, with each passage through a GE or GS space, the particle gains energy.

[0090] For a particle with a Z / A ratio of 1 / 2 (accelerated by the third harmonic of the electric field), the acceleration is maximal when the aperture angle is 60°. For a particle with a Z / A ratio of 1 / 4 (accelerated by the sixth harmonic of the electric field), the acceleration is maximal when the aperture angle is 30°. However, it can be considered that there is a range of aperture angles within which particles with Z / A ratios of 1 / 2 and Z / A ratios of 1 / 4 are accelerated sufficiently efficiently. This range offers a compromise, allowing the acceleration of very different particles with the same accelerating system and the same electric field. An aperture angle range extending between 25° and 40° provides sufficiently efficient acceleration to allow the accelerated particles to reach high energies, enabling the production of alpha and / or p-emitting particles.With these aperture angles, the acceleration of the particles Z / A=1 / 4 remains optimal for the 6th harmonic (the maximum amplitudes of the electric field are located exactly in the GE and GS spaces) and sufficiently efficient for the 3rd harmonic (the maximum amplitudes of the electric field are slightly offset from the GE and GS spaces, but the field is still significant). A narrower range of aperture angles improves the acceleration efficiency of charged particles (and therefore the flux of accelerated particles). For example, the range of aperture angles is between 25° and 35°, or even more preferably, between 28° and 32°. The ideal angle, showing the best results, is 30°.

[0091] Magnetic stiffness is defined as the product of the applied magnetic field B and the radius of curvature p of the charged particle. For a particle of mass A, charge Z and with c the speed of light and Uo the unified atomic mass unit equal to 931.494 MeV. Considering, for example, a final energy W of 8 MeV / nucleon, the magnetic stiffness is 1.632 T m. In this practical implementation, the diameter D of the cyclotron is approximately 230 cm and the average magnetic field at the mid-plane 3 is approximately 3.06 T and the "HF" frequency for "high frequency" of the accelerating electric field is, for example, equal to 70.4 MHz.

[0092] The frequency of the HF electric field, the frequency f, and the magnetic induction B are represented by: B = - - -7 where h is a harmonic of the HF field, U o the unified atomic mass unit. Particle acceleration is performed on the 3rd and 6th harmonics. The optimal opening angle between the GE and GS spaces is 30° (optimal for the 6th harmonic, and also allowing acceleration with the 3rd harmonic).

[0093] Figure 1A shows a top view of the median plane 3 and part of the accelerator system 4. The median plane 3 comprises two regions: a central region 401 and a peripheral region 402. These regions 401 and 402 can also be called "proximal" and "distal." The central (or proximal) region 401 extends in the vicinity of the belly 30 of the median plane 3, and the peripheral (distal) region 402 extends from the central region 401. The central region 401 extends for a distance of approximately 4 cm to 15 cm from the center 30 of the median plane 3. The peripheral region 402 surrounds the central region 401, extending from the central region 401 to an edge of the median plane 3. The edge can be located at a distance from the center 30 of between 40 cm and 150 cm.

[0094] The plurality of electrodes 41, 42 comprises two portions 411, 412, 421, 422, respectively called the "central" portion and the "peripheral" portion, or respectively the "proximal" portion and the "distal" portion, extending respectively into the central region 401 and the peripheral region 402.

[0095] In one embodiment, the central portions 411, 412 of the accelerating and complementary electrodes 41, 42 are removably attached to the peripheral portions 412, 422. Therefore, the central portions 411, 421 of the accelerating and complementary electrodes 41, 42 can be interchanged with other central electrodes to accelerate ions with a different Z / A ratio or according to a different acceleration harmonic. This attachment between the central and peripheral electrodes can be achieved using screws.

[0096] In the illustrated examples, the accelerating electrodes 41 of the accelerating system 4 are electrically connected to each other, at the central region 401 of the median plane 3. The complementary electrodes 42 are, for example, connected to ground.

[0097] Figure 5 schematically represents an embodiment of the cyclotron 1 according to the invention, comprising an extraction means 6 for extracting charged particles without the need for a specific extraction channel. Furthermore, this extraction means also enables the production of an intense particle beam with a high Z / A ratio.

[0098] The extraction means 6 is positioned along a path F of the particle beam, preferably when the particles have high energy, for example, 8 MeV / nucleon. The extraction means 6 intersects, for example, the median plane 3 near an edge of the cyclotron 1, and in particular near an edge of the accelerator system 4. The extraction means 6 is configured to increase the Z / A ratio of the charged particles when they interact with it. The extraction means 6 is, for example, a stripper. Such a means includes, for example, a sheet of graphite. The electromagnetic interaction of the graphite sheet with the charged particles passing through it tends to strip electrons from the charged particle. The number of positive charges increases. The effect of a stripper on a particle of 4 Hey +At 32 MeV (i.e., 8 MeV / nucleon), the particle's charge state tends to double. The resulting particle of 4 Hey 2+ Therefore, it presents a doubled Z / A ratio, that is, equal to 1 / 2 (instead of the initial 1 / 4). The same is true for an ion 12 C 3+ at 96 MeV which, after interaction with the stripper, can exhibit a charge state of up to 6+. The resulting ion 12 C 6+ then presents a doubled Z / A ratio, equal to 1 / 2.

[0099] The extraction means 6 is located in a zone 222 of the median plane 3 in which the azimuthal modulation of the magnetic field B reaches a minimum, at least locally. This zone 222 is therefore necessarily bounded by two other adjacent zones 221 in which the azimuthal modulation of the magnetic field B reaches a maximum, at least locally. Considering the magnetic stiffness of a particle with a ratio Z / A, it is observed that an increase in Z / A tends to proportionally reduce the radius of curvature p of the charged particle's trajectory. The charged particle thus follows a reentrant trajectory F, as shown in Figure 5. In a zone of strong magnetic field B, the radius of curvature decreases and the trajectory F returns towards the center, avoiding contact with the electrodes 41, 42 of the central region 401, and subsequently enters a zone 222 where the magnetic field B is weaker.In this area 222 of low magnetic field B, the radius of curvature increases allowing the particle to move towards the outer edge of the accelerating system 4. By placing a window 8 on this trajectory F, it is possible to extract the charged particles without having to use a specific extraction channel.

[0100] The interaction, for example, of the molecular ion FV or Ü2 + (also called "molecular deuterium," deuterium being an isotope of hydrogen whose nucleus, the deuteron, is composed of a proton and a neutron), with extraction method 6, tends to break the charged molecule (FV gives two H ions) + , and Ü2 + gives two D ions + ). Therefore, the charged particles, in this case protons or deuterons, are released. In the case of the F molecule, the Z / A ratio of the bound protons changes from Z / A = 1 / 2 to Z / A = 1 / 1 when they are released. In the case of the Ü2 molecule +, the Z / A ratio of bound deuterons changes from Z / A = 1 / 4 to Z / A = 1 / 2 when they are released.

[0101] Figure 5 shows an illustration of the simulations performed on cyclotron models 1 according to the invention. The charged particles Z / A=1 / 4 (for example 4 Hey + , Ü2 + or 12 C 3+ ), exhibit, after interaction with the extraction means 6, a Z / A ratio of 1 / 2. Since these particles have equal Z / A ratios, the trajectories from the extraction means 6 are identical, allowing the use of the same beamline at the exit of cyclotron 1.

[0102] In one embodiment, the cyclotron 1 may also include a magnetostatic gradient corrector 48, for example placed upstream of the exit of the cyclotron 1 before passing through the window 8 in the yoke, so as to correct a horizontal focusing (i.e. in the median plane 3) of the extracted beam 9.

[0103] In one embodiment, the cyclotron 1 can include several extraction means 6 used simultaneously and in particular, as many extraction means 6 as there are zones 222 where the modulation of the magnetic field B reaches a low value (called "valleys").

[0104] Having several means of extraction 6 allows, for example, the supplying of several distinct beamlines.

[0105] Each extraction means 6 can be mounted on a rod inserted in a direction, for example, perpendicular to the median plane 3, so that the extraction means is retractable. The rod can include a plurality of strippers to allow for rapid replacement should one of them be damaged.

[0106] Cyclotron 1 can be part of a high-energy particle production line. Cyclotron 1 has an injection line 31 fed by one or more ion sources 32 having a Z / A ratio of 1 / 4. The source(s) 32 are, for example, capable of producing ions such as 4 Hey + , 12 C 3+ or ionized molecules such as Ü2 + The injection line 31 can also be supplied by one or more other ion sources 32, configured to produce weakly ionized ions or molecules having a Z / A ratio of 1 / 2, such as 2H + .

[0107] The injection line 31 is preferably located along an axis of the cyclotron 1, allowing charged particles to be injected at the center 30 of the cyclotron 1's median plane 3 so that they can be accelerated. In the example shown in Figure 6, it is supplied by three different ion sources 32. In this way, it is possible to accelerate at least three different types of ions with the cyclotron 1. The ion sources 32 are, for example, installed in high-voltage platforms. Two ion sources 32 followed by their low energy beam transfer optics (LEBT) are placed in the same plane, for example horizontal, and on either side of the injection line 31. A magnetic dipole 33 can be installed and configured to deflect the particle beam by 90° towards the cyclotron 1 and, preferably, select the desired charge states for injection.A third source 32 can be placed in an axial extension of the injection line 31, not requiring deflection of the particles by the magnetic dipole 33. The cyclotron 1 includes a device, called an "inflector", allowing the injection of particles from the injection line 31 into the median plane 3 by a rotation of the beam by 90°.

[0108] For the production of ions with Z / A = 1 / 4, we will preferentially adopt so-called "ECR" sources (for "Electron Cyclotron Resonance" in English), generally capable of delivering, continuously, an ion flux equivalent to an electric current of several tens of mA in the case of the 4 Hey + and several hundred pA in the case of the 12 C 3+ .

[0109] For the production of Z / A = 1 / 2 ions, a so-called "multicusp" source, capable of generating FV-charged molecules, is preferred. The electric current of the extracted ions is generally on the order of 10 mA. Once accelerated, the FV ion current is generally reduced to about 1.5 mA. Thanks to the extraction method 6 of cyclotron 1, which allows doubling the number of accelerated ions, it is possible to obtain a cyclotron extract current of up to approximately 3 mA of protons.

[0110] Similarly, for the production of molecular deuterium ions at Z / A = 1 / 4, a multi-cusp source capable of generating deuterium molecules charged with Ü2 will be preferred. + .

[0111] p-emitter production lines may include beryllium (Be) targets to generate neutron fluxes capable of driving specific activators (the so-called "ARC" method) for the production of various p-emitting radionuclides. One of the targets may include... 165 Ho.

[0112] Transmitter production lines may include targets for 209 Bi, 226 Ra and / or 142 Nd, depending on the type of nuclear reaction envisaged.

[0113] In addition, independent protection may be sought for an ion production process such as those described above, and more specifically for the production of deuteron ions. This process employs an extraction method configured to increase the Z / A ratio of charged particles when they interact with it (for example, a stripper). The process is carried out, for example, in a cyclotron incorporating such an extraction method, or even advantageously in a cyclotron as described above.

[0114] The production process includes, for example, the following steps: accelerating molecular deuterium ions (D2 + ), these ions having a Z / A ratio equal to 1 / 4; to cause an interaction of said accelerated molecular deuterium ions with the extraction means so as to dissociate each molecular deuterium ion (D2 + ) in deuteron ions (D +The deuteron ions produced have a Z / A ratio of 1 / 2. When molecular deuterium ions have a Z / A ratio of 1 / 4, only one electron is involved in forming the molecular bond between the two deuteron nuclei. Therefore, interaction with the extraction medium removes this bonding electron, resulting in the dissociation of the molecule into two deuteron ions. As mentioned earlier, it is easier to efficiently produce and accelerate ions with a low Z / A ratio (e.g., 1 / 4) to subsequently increase their charge state. Thus, the process allows for the efficient production of ions with a Z / A ratio of 1 / 2.

[0115] For the production of molecular deuterium ions at Z / A = 1 / 4, a multi-cusp source capable of generating deuterium molecules charged with Ü2 will be preferred. + .

[0116] In addition, when the process is implemented in a cyclotron, such as the one described above, the process may include using the reduction of the radius of curvature of the trajectory of said deuteron ions (D + ), resulting from the increase in the Z / A ratio, to cause (or facilitate) their extraction from the cyclotron.

[0117] Molecular deuterium ions are preferentially accelerated to an energy greater than or equal to 16 MeV (in other words, greater than or equal to 4 MeV / nucleon) and preferentially to 32 MeV (in other words, 8 MeV / nucleon). Thus, each deuteron ion produced will have an energy of 8 MeV, or 4 MeV / nucleon (or 16 MeV if the molecular deuterium ions have an initial energy of 32 MeV).

[0118] In a specialization of the radionuclide production process as described above, and in particular of p-emitting radionuclides, it is advantageous to implement the deuteron ion beam production process as described. The radionuclide production process includes, for example, the following steps: producing a deuteron ion beam (D + ) by implementing the aforementioned deuteron ion beam production process; and directing the deuteron ion beam towards at least one target to produce the p-emitting radionuclides.

[0119] In this eventuality, the target is preferentially beryllium.

[0120] The invention is not limited to the embodiments previously described and extends to all embodiments covered by the invention.

Claims

Demands 1. isochronous cyclotron (1) configured to accelerate charged particles having a charge state Z and a number of nucleons A and whose ratio Z / A is equal to 1 / 4 or equal to 1 / 2, the cyclotron being characterized in that it comprises a radiofrequency accelerating system (4), of periodicity three, comprising, and being preferably composed of, three electrodes (41), called "dice", intended to be connected to an oscillating radiofrequency electrical voltage, and three other electrodes (42), called "anti-dice", intended to be connected to the electrical ground, the anti-dice (42) forming, with the three dice (41), six spaces (GE, GS), called accelerating spaces, within which the charged particles are intended to be accelerated, the accelerating spaces each having a proximal portion (GEP, GSP) extending from a neighborhood of a center (30) of the cyclotron (1) and a distal portion (GED, GSD) extending from the proximal portion (GEP,GSP) and substantially along a main radial direction, the three dice (41) being electrically connected to each other in the vicinity of the center (30) of the cyclotron (1) so as to form a single radiofrequency cavity (40), for each die (41), the main directions of two adjacent accelerating spaces (GE, GS) form between them an angle ( ), called the "opening angle", between 25° and 40°.

2. Cyclotron (1) according to the preceding claim, in which the opening angle ( ) is between 25° and 35°.

3. Cyclotron (1) according to the preceding claim, wherein the opening angle ( ) is between 28° and 32° and ideally 30°.

4. Cyclotron (1) according to the preceding claim, comprising a magnetic field (B) exhibiting an azimuthal modulation, invariant over a periodicity of three.

5. Cyclotron (1) according to the preceding claim, comprising a voltage source, referred to as "high frequency", configured to apply an electric field to each die (41), said electric field having a frequency HF such as : where B is the magnetic field induction, U o is a unified atomic mass unit of the charged particles intended to be accelerated by the cyclotron (1), c is the speed of light in a vacuum, and h is a harmonic of a frequency cyc of revolution of the charged particles in the cyclotron (1), said frequency cyc of revolution exhibiting at least two harmonics h0 and h F such that hZ / A is constant for h = 6. Cyclotron (1) according to the preceding claim, in which h0 = 3 and h F = 6.

7. Cyclotron (1) according to any one of the preceding claims, comprising at least one extraction means (6) configured to increase the Z / A ratio of charged particles when they interact with said extraction means (6), preferably at high energy, each extraction means (6) being arranged in the cyclotron (1) to intersect a trajectory of the charged particles when they are accelerated by said cyclotron (1), 8. Cyclotron (1) according to the preceding claim, taken in its dependence with claim 4, in which each extraction means (6) is disposed at the level of a local minimum of the azimuthal modulation of the magnetic field (B).

9. Cyclotron (1) according to any one of the preceding claims, wherein the average magnetic field induction (B) is between 3 T and 3.5 T.

10. Cyclotron (1) according to any one of the preceding claims, comprising a superconducting coil configured to generate a magnetic field induction (B) compatible with a molecular hydrogen dissociation rate of less than 2.10 -3 .

11. Cyclotron (1) according to any one of the preceding claims, comprising an injection line (31) of charged particles in a plane of symmetry (3) of the cyclotron (1), referred to as the "median plane", the injection line (31) being disposed in an axis of the cyclotron, said axis of the cyclotron being an axis around which the magnetic field (B) exhibits rotational invariance of order three.

12. Cyclotron (1) according to the preceding claim, comprising at least two sources (32) of charged particles, one of the sources (32) being configured to produce charged particles having a Z / A ratio of 1 / 2 and another of the sources (32) being configured to produce charged particles having a Z / A ratio of 1 / 4, the at least two sources (32) being mounted on the injection line (31) so as to permit the injection of the charged particles produced into the median plane (3) of the cyclotron (1).

13. A process for producing alpha and beta-emitting radionuclides preferably for medical use, comprising the following steps carried out using a cyclotron (1) according to any one of the preceding claims; • inject a beam of charged particles having a Z / A ratio equal to 1 / 4 or equal to 1 / 2 into a plane of symmetry (3) of the cyclotron (1); • direct the beam of accelerated charged particles towards at least one target.

14. A production method according to the preceding claim, wherein the beam of charged particles having a Z / A ratio equal to 1 / 4 comprises 4 Hey + and / or of the 12 C 3+ and / or of the Ü2 + , and the beam of charged particles having a Z / A ratio equal to 1 / 2 includes FV.

15. A process for producing a deuteron ion beam from molecular deuterium ions having a charge state Z, a nucleon number A, and a Z / A ratio of 1 / 4, the process being carried out in a cyclotron (1) comprising an extraction means (6) configured to increase the Z / A ratio of the molecular deuterium ions when they interact with it, the production process comprising the following steps: • accelerate molecular deuterium ions; • to induce an interaction of said accelerated molecular deuterium ions with the extraction means so as to dissociate the molecular deuterium ions into a plurality of deuteron ions in order to form said deuteron ion beam.

16. A method for producing a deuteron ion beam according to the preceding claim, configured to accelerate molecular deuterium ions to an energy greater than or equal to 16 MeV.

17. A method for producing a deuteron ion beam according to any one of the two preceding claims, wherein the cyclotron (1) comprises a magnetic field (B) having an azimuthal variation so as to form sectors of weak magnetic field (222); and wherein the interaction of said accelerated molecular deuterium ions with the extraction means (6) is carried out in one of said sectors of weak magnetic field (222).

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