HIGH-INTENSITY MULTI-PARTICULAR CYCLOTRON FOR THE INDUSTRIAL PRODUCTION OF α and β RADIONUCLIDES

Abstract

Title: HIGH-INTENSITY MULTI-PARTICULAR CYCLOTRON FOR THE INDUSTRIAL PRODUCTION OF α AND β- RADIONUCLIDES. The invention relates to a cyclotron for the production of α or β- emitting radionuclides. The cyclotron, with a magnetic periodicity of 3, comprises three accelerating cavities connected at the center, thus eliminating the need for phase control between the cavities, forming a single high-frequency resonator. The 6 accelerating spaces per revolution allow for rapid acceleration (the angle ϕ between the accelerating spaces of each cavity is approximately 30°), essential for acceleration in the 3rd and 6th harmonics. This cyclotron preferably has an injection system (31) powered by various types of ion sources, enabling the efficient acceleration of charged particles with Z / A ratios of 1 / 2 and 1 / 4.The cyclotron can also be equipped with stripping extraction devices positioned within it to extract charged particles and double their charge state. These particles allow for the execution of a range of nuclear reactions for the production of α- and β-emitting radionuclides. See Figure 4B for the abbreviation.

Description

Title of the invention: HIGH-INTENSITY MULTI-PARTICULAR CYCLOTRON FOR PRODUCTION INDUSTRIAL RADIONUCLEIDES a and P technical field

[0001] The present 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. STATE OF THE ART

[0002] The rapid development of personalized medicine relies on "theranostics," a neologism that combines therapy and diagnosis. This type of targeted therapy uses alpha and [3-]emitting radionuclides.

[0003] α emitters are, for example, At-211 (denoted At-211 or 21 *At), Terbium-149 (denoted Tb-149 or 149Tb), or Actinium-225 (denoted Ac-225 or 225Ac). 3- emitters are, for example, Lutetium-177 (denoted Lu-177 or 177Lu), Terbium-161 (denoted Tb-161 or 161Tb), or Holmium-166 (denoted Ho-166 or 166Ho).

[0004] [3-] emitters are generally produced by neutron capture in specific nuclear reactors. However, this method of producing [3-] emitters can pose logistical problems for supplying nuclear medicine centers.

[0005] It is known that alpha emitters can be obtained using cyclotron-type particle accelerators, in particular by bombarding specific targets with 4He2+, H+, or 12C6+ ions. [3-] emitters are obtained by bombarding specific targets with intense beams of high-energy H+ or D+ ions (protons and deuterons) (in the 40 to 20 MeV range), producing nuclear reactions on specific targets.

[0006] The production of the different emitters [3- can also be carried out 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.

[0007] These methods have the advantage of being able to be implemented in a facility close to nuclear medicine centers. On the other hand, they require the upstream production of different types of charged particles, these particles then being accelerated (for example by means of a cyclotron).

[0008] An installation for producing emitters of different types generally comprises a cyclotron and beamlines feeding specific production targets of alpha-emitting radionuclides or [3-] emitters. SUMMARY

[0009] To resolve, at least partially, the aforementioned technical problems, the invention provides for an isochronous cyclotron configured to accelerate charged particles having a charge state Z and a number of nucleons A and whose Z / A ratio is equal to 1 / 4 or equal to 1 / 2, the cyclotron being remarkable in that it comprises: - a magnetic field exhibiting an azimuthal modulation, invariant according to a periodicity of three; - a radio frequency accelerator system, with a periodicity of 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.

[0010] 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 center of the cyclotron 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 center of the cyclotron so as to form a single radiofrequency cavity, and for each die, the main directions of two adjacent accelerating spaces form between them an angle, called the "opening angle", between 25° and 40°, preferably between 25° and 35°, even more preferably between 28° and 32° and ideally 30°.

[0011] Connecting the accelerating electrodes to the center of the cyclotron creates a radio-frequency 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 particle rotation frequency (usually difficult to use due to phase fluctuations between the electrodes).

[0012] The opening angle between the accelerating spaces allows for the efficient acceleration of particles exhibiting: - 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.

[0013] 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 several production lines. Each production line aims, for example, to produce alpha emitters or [3-] 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 [3-] emitter production facilities.

[0014] The invention also relates to a method for producing α and β- emitting radionuclides, preferably for medical use, comprising the following steps carried out using a cyclotron according to the invention; - inject a beam of charged particles having a Z / A ratio equal to 1 / 4 or equal to 1 / 2 into the plane of symmetry of the cyclotron; - direct the beam of accelerated charged particles towards at least one target. BRIEF DESCRIPTION OF THE FIGURES

[0015] 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:

[0016] Figs.1A and 1B represent 3-dimensional views of the magnet.

[0017] Figure 2 represents an example of an accelerating system such that it can be put into work in a cyclotron according to the invention.

[0018] Fig. 3 represents a magnification of the accelerating system of Fig. 2.

[0019] Fig.4A and Fig.4B represent, schematically, the accelerating system of Fig.2 and an example of a trajectory that can be followed by ions during their acceleration by the cyclotron.

[0020] Fig. 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.

[0021] Figure 6 represents an example of an injection line comprising three ion sources.

[0022] The drawings are given by way of example and are not limiting of the invention. They constitute schematic representations of principle intended to facilitate the Understanding of the invention and are not necessarily at the scale of practical applications. In particular, figures 2 to 6 are not representative of reality. DETAILED DESCRIPTION

[0023] Before beginning a detailed review of embodiments of the invention, optional features which may possibly be used in association or alternatively are stated below.

[0024] Advantageously, the cyclotron comprises 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.

[0025] In one embodiment, the cyclotron includes a voltage source, referred to as "high frequency" m, configured to apply an electric field to each die (41), said electric field having a frequency such that:

[0026] Bc^ Z _ 2gfHF Uo A- h

[0027] where B is the induction of a magnetic field, Uq is a unified atomic mass unit of the 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 revolution frequency fcyc of the charged particles in the cyclotron, said revolution frequency fcyc having at least two harmonics h® and Ai such that hZ IA is constant for h = Ùq and Z / A = 1 / 2 and for h = and Z / A = 1 / 4.

[0028] In a cyclotron development, hQ = 3 and = 6.

[0029] In one embodiment, the cyclotron includes a line for injecting charged particles in 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.

[0030] 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.

[0031] In one embodiment of the cyclotron, the three accelerating electrodes are galvanically connected.

[0032] The use of a cyclotron requires the upstream production of various types of charged particles in ion sources that produce intense beams. These high-performance sources are external, and specific devices allow the ions to be injected into the cyclotron for acceleration. The production of such ions can be carried out in different types of sources.

[0033] For example, the production of 4He2+ or 12C6+ ions 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 4He 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 12C3+ ions than 12C6+ ions. For example, an ECR source can produce 300 mA (emA) of 12C3+, compared with 30 emA for the completely ionized 12C6+. The number of ions with a high state of charge (e.g., 12C6+) that can be produced is therefore small. Therefore, the number of emitters that can be produced from these ions is small.Today, this production method cannot meet the growing demand from nuclear medicine centers.

[0034] There is therefore a need to increase the production of emitters by increasing the performance of cyclotrons and for the production of emitters [3- controlled by a cyclotron, that is to say without requiring implementation in a nuclear reactor.

[0035] There is therefore a need to increase the production of α and / or [3- emitters (the latter are currently produced in nuclear reactors).

[0036] 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 the level of a local minimum of the azimuthal modulation of the magnetic field.

[0037] Increasing the charge state by stripping the charged particles induces a reduction in the radius of curvature of their trajectory in the median plane. They then describe a reentrant trajectory towards the center of the cyclotron. Indeed, after interacting with this stripper, which is the extraction means, the particles cross a zone (called a "hill") where the magnetic field is higher, immediately adjacent to the area (called the "valley") where the magnetic field is weaker and where the extraction mechanism 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 complete a half-turn inside the cyclotron to reach the magnetic field valley again, where the Laplace force is weaker. The radius of curvature of the particles' trajectory increases. The particles' trajectory straightens, and they then move towards the edge of the cyclotron magnet pole from where they can be extracted.

[0038] The extraction means thus makes it possible to extract the charged particles from the cyclotron without resorting to a specific extraction channel.

[0039] 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.

[0040] It is therefore not necessary to inject particles already exhibiting a high charge state. Particles with a low charge state, such as He, C, or 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.

[0041] Increasing the Z / A ratio corresponds, for example, to doubling this ratio.

[0042] 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.

[0043] In one embodiment of the cyclotron, the average magnetic field induction (B) is between 3 T and 3.5 T.

[0044] 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 2.103.

[0045] In one embodiment, the method comprises, preferably simultaneously with the injection of the beam of charged particles, an application of an oscillating radio frequency electrical voltage on the dice of the cyclotron to accelerate the injected charged particles.

[0046] In one embodiment of the process, the charged particle beam having a Z / A ratio of 1 / 4 comprises 4He+ and / or 12C3+ and / or D2+, and the charged particle beam having a Z / A ratio of 1 / 2 comprises H2+.

[0047] By "isochronous acceleration", we mean acceleration by means of an alternating electric field at a constant frequency.

[0048] By "invariant with respect to a periodicity of three", we mean for example invariant with respect to a rotation of order three.

[0049] By "object having a periodicity of three", we mean an object whose shape exhibits invariance under rotation of order three.

[0050] 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.

[0051] By “static magnetic field”, we mean a magnetic field which does not vary over time.

[0052] By "high energy" is meant energies beyond the threshold of the nuclear reactions for the production of the specific radionuclides envisaged. This is, for example, 4 MeV / nucleons, or 8 MeV / nucleons or even more.

[0053] By “high frequency” is meant a frequency greater than 10 MHz and preferably between 30 MHz and 150 MHz, for example equal to 70 MHz.

[0054] 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.

[0055] By "increasing a charge-to-mass ratio of a charged particle", we mean increasing an absolute value of the charge-to-mass ratio.

[0056] By "unified atomic mass unit", we mean 931.494 MeV / c2.

[0057] Figures IA and IB represent 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 can be ions, light or heavy, or partially ionized molecules (such as molecular dihydrogen H2+). These charged particles are accelerated along trajectories F having, at least in part, a spiral shape extending along a plane 3 called the "median plane".

[0058] 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 particle's charge and to the intensity of the magnetic field in which the particles are immersed, and is inversely proportional to the mass of the particles).

[0059] To maintain isochronism with increasing charged particle speeds, one solution is to modulate a 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.

[0060] 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.

[0061] The median plane 3 is preferably a plane of symmetry of the magnetic field source. In this way, 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 comprises, for example, a superconducting coil configured to generate a magnetic field induction (B) compatible with a molecular hydrogen dissociation rate of less than 2 x 10³. This reduces high-intensity beam losses to an acceptable level at high energy.

[0062] 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 2ir / 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". The rotational invariance of the third order is obtained, for example, by means of an arrangement of the 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") corresponding to the weak field and are arranged between the hills 221.

[0063] The median plane 3 includes a center 30 in the vicinity of which the charged particles intended to be accelerated 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.

[0064] The cyclotron 1, as shown in [Fig. 1A] and 2, includes a resonant cavity 40, also called an RF cavity (for "Radio Frequency," such cavities generally being 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.

[0065] The resonant aspect of the RF cavity 40 allows the high-frequency electric field to be amplified when it is close to the resonance frequency of the cavity 40. The acceleration of the charged particles in the cyclotron 1 is thereby improved.

[0066] Using a single RF cavity 40 offers a considerable advantage by eliminating the need for phase control of the electric field. Indeed, prior art cyclotrons generally comprise several separate RF cavities, each requiring phase control. However, poor phase control inevitably leads to a reduction in the efficiency of charged particle acceleration. This, in turn, reduces the intensity of the accelerated particle flux. Precise phase control of RF cavities is all the more important when the harmonics considered for particle acceleration are high. Accelerating particles using the h = 6 harmonic is difficult, particularly when the number of revolutions made by the particles is significant.Thus, the use of a single RF cavity 40 allows the phase of the electric field to be regulated throughout the cavity without requiring precise control of the cavity itself. The single RF cavity therefore enables efficient acceleration on the 6th harmonic.

[0067] The RF cavity 40 is special in that it is formed by three conducting electrodes 41, also called "accelerating electrodes" or "dee." The accelerating electrodes 41 extend preferably 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, in particular, to the charged particles so as to accelerate them.

[0068] In the absence of an electrical connection between the electrodes 41, each accelerating electrode 41 can form an independent radio frequency resonant cavity, 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 to each other. The electrodes 41 They can be electrically connected using 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's resonance. To overcome this drawback, the electrodes 41 are preferentially 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 vicinity is preferably determined from the projection of the electrodes 41 onto the median plane 3. The vicinity 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 cavity 40 can be easily calculated. It is not necessary to take into account the length and impedance of the transmission line.

[0069] 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.

[0070] 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.

[0071] The electrodes 41 and the complementary electrodes 42 (or respectively dice and anti-dice) can have different shapes allowing the application of an electric field in the median plane 3. For example, they can be partially curved to form U-shapes. They are then 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 embodiment, 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. [Fig. 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 part by part without encountering obstacles.

[0072] The accelerating electrodes 41 and complementary electrodes 42 are arranged alternately in a circular arrangement. 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 gaps GE, GS, also called accelerating gaps. Cyclotron 1 is configured so that charged particles are accelerated within these accelerating gaps GE, GS. The accelerating gaps GE, GS are essentially empty spaces between the accelerating electrodes 41 and the complementary electrodes 42, within which the electric field is established to accelerate the charged particles.

[0073] Each accelerating space GE, GS exhibits, at least in part, a substantially radial orientation. By "radial orientation" is meant an orientation aligned along a ray passing through the center 30 of the median plane 3. By "substantially radial" is meant oriented parallel to the ray passing through the center 30 of the median plane 3, to within + / - 20°, or even + / - 10°. This substantially radial orientation may vary along each accelerating space GE, GS. The substantially radial orientation will be considered to be 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.

[0074] One of the accelerating gaps GE 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 accelerating gaps GS 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).

[0075] The single 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 4L. 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 through the RF cavity 40 without the need to control phase between different generators.

[0076] Fig. 5 shows, for example, that the central space of the electromagnet 21 is structured so as 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.

[0077] 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 [Fig. 4A], these are charged particles (ions or ionized molecules) with an elementary charge number Z (also called "charge state") and a total number of nucleons A (particularly in the case of ionized molecules) such that Z / A = 1 / 4. Examples include 4He+ or 12C3+ particles. In the case of [Fig. 4B], these are particles with a Z / A = 1 / 2. Examples include H2+ or D2+ ("D" stands for deuterium - also written as 2H). Cyclotron 1 is remarkable in that it allows for the efficient acceleration of both particles with a Z / A = 1 / 4 and particles with a Z / A = 1 / 2 without changing accelerator systems 4.

[0078] An example embodiment allows for the acceleration of ions with a Z / A ratio of 1 / 4 (for example, D2+ molecular ions, 4He+ and 12C3+ ions). A positive 4He+ ion is a helium atom that has lost a single electron. In this case, Z = 1. The 4He+ ion comprises 4 nucleons (A = 4). The electric charge-to-mass ratio, which we will denote as Z / A in the following description, is therefore equal to 1 / 4 in the case of the 4He+ ion. It is also possible to consider the 12C3+ ion (whose Z / A = 1 / 4). An H2+ molecular ion comprises two protons and one electron. The equivalent Z / A ratio is 1 / 2.

[0079] 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 means of 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 means of the sixth harmonic (h = 6) of the particle frequency.

[0080] 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 which nevertheless proves correct for at least part 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 α) corresponds to the angle formed between consecutive accelerating spaces GE, GS, that is, those arranged on either side of the same accelerating electrode 4L.

[0081] The distal portions GED, GSD of the accelerating spaces GE, GS are preferably considered. The distal portion of each accelerating space GE, GS is preferably linear. Alternatively, it may not be linear, as shown in [Fig. 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.

[0082] 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 rectilinear, 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.

[0083] 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, GS spaces, and particularly when the distance between these GE, GS spaces corresponds to the flight time of the charged particle on the trajectory F. Thus, with each passage through a GE, GS space, the particle gains energy.

[0084] For a particle with a Z / A ratio of 1 / 2 (accelerated by the third harmonic of the electric field), the acceleration is maximum when the opening angle ¢) is equal to 60°. For a particle with a Z / A ratio of 1 / 4 (accelerated by the sixth harmonic of the electric field), the acceleration is maximum when the opening angle ¢) is equal to 30°.

[0085] However, it can be considered that there exists a range of aperture angles in which the Z / A = 1 / 2 and Z / A = 1 / 4 particles are accelerated sufficiently efficiently. This is a range that offers a compromise allowing the acceleration of very different particles with the same accelerating system 4 and the same electric field. A range of aperture angles extending between 25° and 40° makes it possible to obtain sufficiently efficient acceleration to allow the accelerated particles to reach high energies enabling the production of alpha and / or [3-] emitters. With these opening angles ¢, the acceleration of the particles Z / A=l / 4 remains optimal for the 6th harmonic (the maxima 46 and minima 47 of amplitude of the electric field are located exactly on the GE and GS spaces) and sufficiently efficient for the 3rd harmonic (the maxima 46 and minima 47 of amplitude are located slightly offset with respect to the GE and GS spaces but the field is still significant).A narrower range of aperture angles improves the efficiency of accelerating charged particles (and therefore the flux of accelerated particles). For example, the range of aperture angles is between 25° and 35°, preferably between 28° and 32°. The ideal angle, showing the best results, is 30°.

[0086] 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 energy W: R n_ 1 A &'p — cz

[0087] 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 Tm. In this practical embodiment, the diameter D of the cyclotron is approximately 230 cm and the average magnetic field at the median 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.

[0088] The frequency of the HF electric field, the frequency f and the magnetic induction B are related by: R _ A 2nf uo D~ Z h c2

[0089] where h is a harmonic of the HF field, Uq the unified atomic mass unit. The acceleration of the particles is carried out on the 3rd and 6th harmonics. The optimal opening angle ¢) between the GE, GS spaces is 30° (optimal for the 6th harmonic, and allowing acceleration also with the 3rd harmonic).

[0090] Fig. 1A represents, in top view, the median plane 3 and part of the accelerating system 4. The median plane 3 comprises two regions, including a central region 401 and a peripheral region 402. These regions 401, 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.

[0091] 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.

[0092] 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 in order to accelerate ions having 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.

[0093] In the illustrated examples, the accelerating electrodes 41 of the accelerator system 4 are electrically connected to each other, at the level of the central region 401 of the median plane 3. The complementary electrodes 42 are, for example, connected to ground.

[0094] 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 makes it possible to produce an intense beam of particles having a high Z / A ratio.

[0095] The extraction means 6 is positioned along a trajectory 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 in the vicinity of an edge of the cyclotron 1, and in particular 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 4He+ particle at 32 MeV (i.e. 8 MeV / nucleon) tends to double the charge state of the particle.The resulting 4He2+ particle therefore has a doubled Z / A ratio, that is, equal to 1 / 2 (instead of the initial 1 / 4). The same is true for a 12C3+ ion at 96 MeV which, after interaction with the stripper, can exhibit a charge state of up to 6+. The resulting 12C6+ ion then has a doubled Z / A ratio, equal to 1 / 2.

[0096] The extraction means 6 is disposed 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. Thus, this zone 222 is 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 therefore follows a reentrant trajectory F, as shown in [Fig. 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 weak magnetic field B, the radius of curvature increases allowing the particle to move towards the outer edge. of the accelerator 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.

[0097] The interaction, for example, of the molecular ion H2+ or D2+ (also called "molecular deuterium," deuterium being an isotope of hydrogen whose nucleus, the deuteron, is composed of a proton and a neutron), with the extraction means 6, tends to break the charged molecule (H2+ yields two H+ ions, and D2+ yields two D+ ions). Consequently, the charged particles, here protons or deuterons, are released. In the case of the H2+ molecule, the Z / A ratio of bound protons changes from Z / A = 1 / 2 to Z / A = 1 / 1 when they are released. In the case of the D2+ molecule, the Z / A ratio of bound deuterons changes from Z / A = 1 / 4 to Z / A = 1 / 2 when they are released.

[0098] Figure 5 shows an illustration of the simulations carried out on models of cyclotron 1 according to the invention. The charged particles Z / A=1 / 4 (for example 4He+, D2+ or 12C3+), after interaction with the extraction means 6, have 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 the cyclotron 1.

[0099] 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.

[0100] In one embodiment, the cyclotron 1 may 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").

[0101] Having several means of extraction 6 allows, for example, to feed several distinct beam lines.

[0102] 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 may include a plurality of strippers to allow for rapid replacement should one of them be damaged.

[0103] The cyclotron 1 can be part of a high-energy particle production line. The 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 4He+, 12C3+ or ionized molecules such as D2+. The injection line 31 can also be fed 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+.

[0104] The injection line 31 is preferably located along an axis of the cyclotron 1, allowing the charged particles to be injected at the center 30 of the median plane 3 of the cyclotron 1 so that they can be accelerated. In the example of [Fig. 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 90° rotation of the beam.

[0105] For the production of ions with Z / A = 1 / 4, preferred sources will be called "ECR" (for "Electron Cyclotron Resonance" in English), generally capable of delivering, continuously, a flux of ions equivalent to an electric current of several tens of mA in the case of 4He+ and several hundred uA in the case of 12C3+.

[0106] For the production of Z / A = 1 / 2 ions, a so-called "multicusp" source, capable of generating H2+ charged molecules, is preferably used. The electric current of the extracted ions is generally on the order of 10 mA. Once accelerated, the current of the H2+ ions is generally reduced to about 1.5 mA. Thanks to the extraction method 6 of the cyclotron 1, which allows the number of accelerated ions to be doubled, it is possible to obtain a current extracted from the cyclotron of up to about 3 mA of protons.

[0107] Similarly, for the production of molecular deuterium ions at Z / A = 1 / 4, a multicusp source, capable of generating deuterium molecules charged with D2+, will be preferred.

[0108] The [3- emitter production lines may include Be (beryllium) targets to generate neutron fluxes capable of driving specific activators (the so-called "ARC" method) for the production of different [3- emitting radionuclides. One of the targets may include 165Ho.

[0109] The emitter production lines may include targets of 209Bi, 226Ra and / or 142Nd, depending on the type of nuclear reaction envisaged.

[0110] The invention is not limited to the embodiments previously described and extends to all embodiments covered by the invention.

Claims

Demands

1. An isochronous cyclotron (1) configured to accelerate charged particles having a charge state Z and a number of nucleons A and whose Z / A ratio is equal to 1 / 4 or equal to 1 / 2, the cyclotron being characterized in that it comprises: • a magnetic field (B) having an azimuthal modulation, invariant with a periodicity of three; • a radio-frequency accelerating system (4), with a periodicity of three, comprising, and preferably being composed of, three electrodes (41), called "dice", intended to be connected to an oscillating radio-frequency electrical voltage, and three other electrodes (42), called "anti-dice", intended to be connected to 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, each accelerating space having a proximal portion (GEP,GSP) extending from a vicinity 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°, preferably between 25° and 35°, even more preferably between 28° and 32° and ideally 30°.

2. 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 such that: Bc2 Z _ 2nfHF Uo A “ h where B is the induction of a magnetic field, Uq 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 the empty, and h is a harmonic of a revolution frequency fcyc of the charged particles in the cyclotron (1), said revolution frequency fCyc having at least two harmonics h® and Ai such that hZ / A is constant for h = and Z / A = 1 / 2 and for h = and ZlA = 1 / 4.

3. Cyclotron (1) according to the preceding claim, in which / îq = 3 and hr = 6.

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

5. 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.

6. 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.

103.

7. 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.

8. 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).

9. A method 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; • injecting a beam of charged particles having a Z / A ratio of 1 / 4 or 1 / 2 into a plane of symmetry (3) of the cyclotron (1); • directing the beam of accelerated charged particles towards at least one target.

10. A production method according to the preceding claim, wherein the charged particle beam having a Z / A ratio of 1 / 4 comprises 4He+ and / or 12C3+ and / or D2+, and the charged particle beam having a Z / A ratio of 1 / 2 comprises h2+.

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