EP2581914B1 - Method and facility for producing a radioisotope - Google Patents

Description

Technical area

The present invention relates to a method for producing a radioisotope and an installation for carrying out this method.

State of the art

In nuclear medicine, positron emission tomography is an imaging technique that requires positron-emitting radioisotopes or molecules labeled with these same radioisotopes. The ¹⁸ F radioisotope is one of the most commonly used radioisotopes. Other radioisotopes commonly used are: ¹³ N; ¹⁵ O; and ¹¹ C. The ¹⁸ F radioisotope has a half-life of 109.6 min and can thus be transported to other sites than its production site.

¹⁸ F is most often produced in its ionic form. It is obtained by the bombardment of accelerated protons on a target comprising water enriched in ¹⁸ O. Many targets have been developed, all having the same goal to produce ¹⁸ F in a reduced time with the best performance. Generally, a device for producing radioisotopes comprises a proton accelerator and a target cooled by a cooling device. This target comprises a cavity sealed by an irradiation window to form a hermetic cell inside which is included a radioisotope precursor in liquid or gaseous form.

Generally, the energy of the proton beam directed on the target is of the order of a few MeV to about twenty MeV. Such a beam energy causes a heating of the target and a vaporization of the liquid containing the radioisotope precursor. Since the vapor phase has a lower stopping power, more particles of the irradiation beam pass through the hermetic cell without being absorbed by the radioisotope precursor, which decreases not only the production efficiency of the radioisotope. radioisotopes, but also warms the target further. This well-known phenomenon is commonly called tunneling effect.

It is known to reduce the importance of the "tunneling effect" by means of a pressurization system of the hermetic cell, as for example described in the documents WO2010007174 . Such a system pressurizes the hermetic cell of the target with an inert gas, so as to increase the evaporation temperature of the precursor liquid inside the hermetic cell. However, this solution has the disadvantage of having to work with a higher pressure in the hermetic cell of the target, which requires a target designed to withstand higher pressures. Such a target has the disadvantage of having a wall of greater thickness compared to traditional targets. It therefore requires a relatively high beam energy to irradiate the radioisotope precursor.

The document JP2009103611 discloses a device for producing radioisotopes comprising a system for pressurizing the hermetic cell capable of maintaining a constant internal pressure inside the hermetic cell. To avoid breaking the irradiation window due to an increase in pressure, the document JP 2009103611 proposes to equip the hermetic cell with a control valve allowing a controlled discharge of radioisotope precursor fluid if the pressure in the hermetic cell exceeds a threshold value. This solution has the particular disadvantage of causing the loss of volume of radioisotope precursor fluid contained in the hermetic cell. However, some precursor fluids of radioisotopes can be very expensive, so that it is necessary at all costs to avoid untimely discharges. To avoid inadvertent discharges, the working pressure in the sealed cell of the target must be substantially less than the discharge pressure.

When a target for the production of radioisotopes is irradiated daily by a proton beam for several hours, some areas of the target may become weaker over time. The heating of the irradiation cell can thus damage the seals sealing the cavity closed by the irradiation window, causing leaks. Leaks may also appear at the irradiation window. On the other hand, the irradiation of the target produces secondary radiation that can damage nearby parts, such as ducts, valves or a pressure sensor fitted to the target, which also causes leaks. However, if the aforementioned pressurizing device has the advantage of keeping the radioisotope precursor fluid in a condensed or semi-condensed state, possible leaks in the irradiation cell and / or poor filling of the target of the example to a defective valve, can not be detected in time. Indeed, if the device for monitoring the internal pressure in the hermetic cell records a decrease in this pressure, the pressurizing device will normally inject inert gas into the target to re-increase its internal pressure. It will also be noted that impurities resulting from a washing of the target followed by poor drying may also cause an overpressure, which may be masked by the aforementioned pressurizing device.

When irradiating a target that is not sufficiently filled, in addition to the poor yields of radioisotopes obtained, some parts of the target can heat up quickly because of the "tunneling effect" to deform the target, the joints ensuring the watertightness or the irradiation window. Leaks can occur without being detected in time because of the pressurization system which re-increases the internal pressure of the target due to pressure variation.

The higher the degree of filling of the hermetic cell with the radioisotope precursor fluid, the greater the internal pressure in the hermetic cell increases upon irradiation. However, if the internal pressure in the hermetic cell exceeds a certain threshold, this can cause a rupture of the irradiation window, with extremely harmful consequences.

It is therefore also necessary to avoid a rupture of the irradiation window as a result of an increase in pressure than to detect in time problems of leakage or inadequate filling.

Presentation of the invention

An object of the present invention is, in the production of radioisotopes, to detect in time the problems of leakage or poor filling of a target and to avoid deterioration of the target either by said tunneling effect or by an increase in excessive pressure.

This object is achieved by a method according to claim 1, respectively an installation according to claim 10.

A method according to the invention comprises, in a manner known per se, an irradiation of a volume of radioisotope precursor fluid contained in a hermetic cell of a target, this using a particle beam of a given current, which is produced by a particle accelerator. The target is cooled, and internal pressure is measured in the airtight cell. According to one aspect of the invention, the internal pressure (P) is allowed to freely establish itself in the hermetic cell during the irradiation, without trying to control it by an injection of a pressurizing gas and / or a depressurization valve. , and the irradiation is interrupted or its intensity reduced, when the internal pressure (P) in the hermetic cell comes out of a first tolerance interval, which is defined according to different parameters having an influence on the evolution of the internal pressure in the hermetic cell during irradiation. Such parameters include, for a given target and radioisotope precursor fluid, including the degree of filling of the hermetic cell, the cooling power of the target and the beam current (I).

By this way of proceeding, when the pressure falls below the lower limit of the first tolerance interval, the irradiation is interrupted or its intensity is reduced so as to avoid overheating of the target. This lower limit corresponds to an excessively large deviation from an optimum internal pressure determined for a hermetic cell containing a given volume of radioisotope precursor fluid and irradiated by a given beam current.

When the pressure exceeds the upper limit of the first tolerance interval the irradiation is interrupted or its intensity is reduced so as to also prevent a rupture of the irradiation window due to an excessive increase of the pressure in the hermetic cell. This upper limit can indeed be defined so that it represents a sufficient security with respect to the breaking pressure of the irradiation window.

It will be appreciated that this procedure does not require any injection of a pressurizing gas, which would increase the total pressure in the airtight cell, i.e. the nominal pressure for which the target is to be designed, and would also risk hide leaks. It also does not require depressurization by a discharge causing an expensive radioisotope precursor fluid loss.

To interrupt the irradiation or reduce its intensity, it acts normally directly on the particle accelerator. However, it is also possible to act on the particle beam (for example by deflecting the beam or by interposing an obstacle in its path) or on the target (for example by moving it away from the trajectory of the particle beam).

In a preferred manner, a curve P = f (I), providing the internal pressure (P) in the hermetic cell for different beam currents (I), is determined, for example experimentally or with the aid of a mathematical model, this for a given target, a given volume of a given radioisotope precursor fluid and a given cooling power of the target. The first tolerance interval then has a lower pressure limit and an upper pressure limit, defined for the given beam current (I) based on the curve P = f (I). The lower limit of internal pressure is defined so that it is lower, preferably between 5% to 20% lower, than the pressure value deduced from said curve P = f (I) for the beam current. given (I). The upper limit of internal pressure is a pressure between the pressure value derived from the curve P = f (I) for the given beam current (I) and a nominal pressure value (Pmax) of the hermetic cell. This nominal pressure value (Pmax) is supposed to represent the maximum pressure value for which the hermetic cell is guaranteed.

The upper limit of internal pressure of the first tolerance interval is advantageously at least 20% lower than the nominal pressure value (Pmax) of the hermetic cell. This normally provides sufficient security against rupture of the irradiation window.

Preferably, the upper limit of internal pressure of the first tolerance interval is between 5 and 10 bars higher than the pressure value deduced from the curve P = f (I) for the given beam current (I) and is additionally capped at a pressure value (P2) lower than a value of X bar to the nominal pressure value (Pmax) of said hermetic cell. This way of proceeding makes it possible to detect a bad filling of the hermetic cell or of any impurities coming from the washing of the cell and thus to avoid a too fast rise of the pressure with high value of beam current.

A control device advantageously triggers an alarm when the internal pressure (P) in said hermetic cell exits a given second tolerance interval for said given beam current (I), a given volume of radioisotope precursor fluid and a radiating power. given cooling of said target, said second tolerance interval being included in the first tolerance interval. The operator is thus warned that the evolution of the pressure in the hermetic cell may soon cause an interruption of irradiation, and it may possibly still prevent this automatic interruption.

The second tolerance range has a lower pressure limit and an upper pressure limit, based on the P = f (I) curve mentioned above. The lower internal pressure limit of the second tolerance interval is set so that it is lower, preferably at least 2%, than the pressure value derived from said curve P = f (I) for the beam current (I) given, while nevertheless remaining higher than the lower limit of internal pressure of the first tolerance interval. The upper internal pressure limit of the second tolerance interval is set so that it is greater than the pressure value deduced from the curve P = f (I) for the given beam current (I), all remaining below the upper limit of internal pressure of the first tolerance range.

When the internal pressure (P) in the airtight cell exceeds an upper limit of internal pressure which is set so that it is greater than the pressure value deduced from said curve P = f (I) for the current beam (I) given, but lower than the upper limit of internal pressure of the first tolerance interval, advantageously decreases the beam current. In this way it is possible to prevent interruption of the irradiation.

The degree of filling of the hermetic cell is advantageously optimized so as to obtain a high radioisotope production yield.

The radioisotope precursor is advantageously a precursor of ¹¹ C, ¹³ N, ¹⁵ O or ¹⁸ F.

There is also an installation for implementing the method described. This installation comprises a target with a hermetic cell capable of containing a volume of precursor fluid, this hermetic cell being guaranteed to withstand a nominal pressure (Pmax), a particle accelerator capable of producing and directing an accelerated particle beam. a given current (I) on the target, a system for monitoring the internal pressure of the cell hermetic, and a control device programmed to interrupt the particle beam or reduce its intensity when the internal pressure (P) in the hermetic cell comes out of a first tolerance range determined according to different parameters having an influence on the evolution internal pressure in the hermetic cell during irradiation.

The control device is advantageously programmed to trigger an alarm when the internal pressure of the hermetic cell is outside a second interval in said first tolerance range.

The control device may also be advantageously programmed to cause a decrease in the intensity of the beam current when the internal pressure (P) in said airtight cell exceeds an upper limit of internal pressure.

In a preferred embodiment, the control device is programmed with a curve P = f (I), supplying the internal pressure (P) of the hermetic cell for different beam currents (I), for a given volume of precursor fluid. radioisotope and a given cooling power of said target; this curve P = f (I) being used by said control device to determine said first tolerance interval as a function of the beam current (I).

Brief description of the drawings

Fig. 1

est un schéma d'une installation de production de radioisotopes selon la présente invention ;

Fig. 2

est un graphique montrant une courbe expérimentale P =f(I), représentant l'évolution de la pression interne en fonction du courant de faisceau (I), et des courbes d'intervalles de tolérance de pression interne, ceci pour une cible de géométrie donnée, une puissance de refroidissement donnée et un volume de précurseur de radioisotope donné.

Other features and advantages will be apparent from the detailed description of various embodiments of the invention, which are hereinafter described by way of illustration with reference to the accompanying drawings, in which:

Fig. 1

is a diagram of a radioisotope production facility according to the present invention;

Fig. 2

is a graph showing an experimental curve P = f (I), representing the evolution of the internal pressure as a function of the beam current (I), and internal pressure tolerance interval curves, for a geometry target given, a given cooling power and a given radioisotope precursor volume.

Description of Embodiments of the Invention

A non-limiting embodiment of a radioisotope production installation 10 according to the present invention is illustrated on the basis of the diagram of FIG. Fig. 1 . This installation 10 comprises a target, globally identified by the reference sign 12. This target 12 comprises a hermetic cell 14 enclosing a volume of radioisotope precursor fluid. It is equipped, in known manner, with a cooling circuit 16.

The plant 10 further comprises a particle accelerator 18 capable of producing an accelerated particle beam 20 which is directed at the target 12 to irradiate the radioisotope precursor in the airtight cell 14. The beam 20 enters the airtight cell 14 by an irradiation window 22 having a thickness of the order of a few tens of micrometers. The maximum internal pressure that the target 12 can withstand depends in particular on the thickness of this irradiation window. The nominal pressure (Pmax) of the target 12 is the maximum internal pressure in the hermetic cell 14 guaranteed by the producer of the target. As long as the internal pressure in the airtight cell 14 remains below the nominal pressure (Pmax), the producer of the target ensures that the irradiation window 22 is pressure-resistant. This nominal pressure (Pmax) is of course a function of the geometry of the hermetic cell 14.

The reference sign 24 identifies a schematic representation of a pressure sensor, which measures the internal pressure in the hermetic cell 14. A signal representative of this measured pressure is transmitted, for example through a data bus 26, to a control device 28. On the basis of this pressure signal, the control device 28 monitors the pressure in the hermetic cell 14 in a continuous or quasi-continuous manner.

The installation 10 advantageously comprises a multi-way valve 30, which makes it possible to communicate the hermetic cell 14 with different auxiliary equipment. A first port A of this valve 30 is for example connected to a three-way valve 32, itself connected to a reservoir 34 containing the radioisotope precursor and to a pipetting device 36, such as a syringe. A second port B is connected to a first port of the hermetic cell 14 by a conduit 38 for filling and emptying the hermetic cell 14. A third port C is connected to a container 40, intended to receive the irradiated product when the irradiation is complete. A fourth port D is connected to an overflow vessel 42 for collecting the excess fluid introduced into the airtight cell 14. A fifth port E is connected to a second port of the airtight cell 14, via a conduit 44. conduit 44 which serves to evacuate the excess fluid introduced into the hermetic cell 14, respectively to the introduction of a purge gas gas in the hermetic cell 14. This purge gas is contained in a reservoir 46, connected to a sixth port F.

The control system 12 controls the various valves 30, 32, the pipetting device 36, the cooling device 16, the flow of the purge gas cylinder 10 and the particle accelerator 18. When filling the hermetic cell 14, the valve 30 connects the port A with port B and port D with port E. The three-way valve 32 connects reservoir 34 containing the radioisotope precursor with pipetting device 36 which draws a quantity of fluid including the radioisotope precursor. The three-way valve 32 then connects the pipetting device 36 to the port A of the valve 30. The pipetting device 36 can now inject the fluid containing the radioisotope precursor into the airtight cell 14, any excess liquid being discharged. to the overflow vessel 42. When the airtight cell 14 is filled, the valve 30 closes all the ports, and the accelerator 18 produces the beam irradiating the target 12. When the irradiation of the target 12 is complete, the valve 30 connects the port F with the port E, and the port B with the port C, so that the purge gas is injected into the hermetic cell 14, and the irradiated fluid is removed from the target 12 to be then collected in the irradiated product container 40.

It will be noted that during the irradiation operation of the target 12, the internal pressure (P) is freely allowed to establish in the airtight cell 14. This means that no device for adjusting the pressure is required. internal in the airtight cell 14, on the basis of a pressurization system using a pressurizing gas and a depressurization system using a purge valve.

The internal pressure (P) in the airtight cell 14 is measured by the pressure sensor 24 and monitored by the control device 28. When the internal pressure (P) comes out of a first defined tolerance range, the controller 28 interrupts simply irradiating the target 12 or reducing its intensity. It will be noted that, for a given target 12, this first tolerance interval is defined specifically for the current I of the beam 20, the volume V of the radioisotope precursor fluid contained in the hermetic cell 14 and the cooling power of the target 12. (Normally, the cooling power is kept constant.)

The control system 12 is therefore programmed to interrupt the irradiation of the target 12, when the internal pressure (P) in the sealed cell 14 comes out of a first defined tolerance range. It is also advantageously programmed to trigger a prior alarm, and / or reduce the intensity of irradiation, when the internal pressure (P) in the hermetic cell 14 comes out of a second fixed tolerance range, which is included in the first tolerance interval.

An advantageous definition of these tolerance ranges is now described with reference to the Fig. 2 , which shows in particular an experimental curve P = f (I), representing the evolution of the internal pressure (P) in the hermetic cell 14 as a function of the beam current (I), this for a given target 12, a certain volume of radioisotope precursor liquid in the hermetic cell 14 and a certain cooling power of the target 12. The example of curve P = f (I) shown in FIG. Fig. 2 has for example been determined for a hermetic cell 14 of given geometry, a volume of 3.5 ml, filled with a volume of 2.5 ml radioisotope precursor fluid. To record this curve P = f (I), the beam current was gradually increased by measuring the internal pressure of the target using the pressure sensor 24. These measurements were made until the value of nominal pressure (Pmax) guaranteed for the target 12 for a beam current I of approximately 60 pA. During all the measurements, the coolant flow rate was kept substantially constant, as was the coolant inlet temperature in the target 12.

It will be noted that the curve P = f (I) represented on the Fig. 2 does not constitute a limitation of the invention. Indeed, the curve P = f (I) varies according to the quality of the beam produced by the accelerator, the geometry of the target, the cooling power, the volume and the liquid nature precursor radioisotope. The curve P = f (I) can also be determined theoretically by simulation, taking into account the parameters of the beam, the volume of radioisotope precursor fluid, the power of the cooling system and the geometry of the target 1, characteristics radioisotope precursor liquid.

The first tolerance interval has a lower pressure limit and an upper pressure limit, both defined for said given beam current (I) based on the P = f (I) curve. The lower limit of internal pressure is defined so that it is preferably between 5% to 20% lower than the pressure value deduced from the curve P = f (I) for the given beam current (I ). On the Fig. 2 the curve f (I) = P- (0.2 * P) represents for example the case of a lower limit of internal pressure defined so that it is 20% lower than the pressure value deduced of the curve P = f (I) for a given beam current (I). The upper limit of internal pressure is a pressure between the pressure value derived from the curve P = f (I) for the given beam current and a nominal pressure value (Pmax) of the hermetic cell. It is advantageously between 5 and 10 bars higher than the pressure value deduced from said curve P = f (I) for a given beam current (I), and is capped at a pressure value (P2) less than the value nominal pressure (Pmax) of the hermetic cell 14. The curve f (I) = P + 5 on the Fig. 2 represents, for example, the case of an upper limit of internal pressure set so that it or 5 bar higher than the pressure deduced from the curve P = f (I) for a given beam current (I). On the Fig. 2 , the upper limit of internal pressure is preferably limited upwards to a value P2 = 30 bar, which represents 75% of the nominal pressure Pmax, which is equal to 40 bar.

The second pressure range is within the first tolerance range and is also around the curve f (I) = P. The lower internal pressure limit of the second tolerance interval is defined so that it is lower, preferably at least 2%, to the pressure value deduced from the curve P = f (I) for the given beam current (I), while remaining greater than the lower limit of internal pressure of the first interval of tolerance. The upper limit of internal pressure of the second tolerance interval is determined so that it is greater than the pressure value deduced from the curve P = f (I) for the given beam current (I), all remaining below the upper limit of internal pressure of the first tolerance range.

An example of a second tolerance interval is also shown on the Fig. 2 . The lower limit of internal pressure is represented by the curve f (I) = P- (0.1 * P) and the upper limit of internal pressure is represented by the curve f (I) = P + 2.

The control device 12, which also controls the intensity of the beam current, is advantageously programmed to cause a decrease in the intensity of the beam current when the internal pressure (P) in the airtight cell 14 exceeds an upper limit of internal pressure. This upper limit is then defined so that it is greater than the pressure value deduced from said curve P = f (I) for the beam current. (I) given but less than the upper limit of internal pressure of said first tolerance range.

To optimize the process, it is possible in particular to play on the degree of filling of the airtight cell 14. Indeed, in order to optimize the production yield of radioisotopes, it is useful to optimize the degree of filling of the airtight cell. By knowing the value of the nominal pressure (Pmax) of the hermetic cell, while measuring the internal pressure of the hermetic cell, irradiating for a defined period (for example two hours), for different volumes of radioisotope precursor fluid, the target with a beam current I so as not to exceed the nominal pressure (Pmax). The yield of radioisotopes produced for each of the volumes is then calculated. A radioisotope production efficiency curve is plotted against the degree of cell filling which in practice shows a constant yield above a critical degree of filling and a large yield drop below that same degree of filling. critical. In order to minimize the pressure stresses in the target, while minimizing the tunneling effect, a degree of filling of the hermetic cell corresponding to this degree of critical filling or a slightly higher degree of filling is established. either experimentally or theoretically the curve of the pressure P as a function of the beam current I for this degree of filling of the hermetic cell.

It should be noted that the installation and the method described are particularly suitable for producing radioisotopes such as ¹¹ C, ¹³ N, ¹⁵ O or ¹⁸ F. <b> List of reference signs </ b> 10 radioisotope production facility 32 three way valve 34 tank containing the radioisotope precursor 12 target 14 hermetic cell 36 pipetting device 16 cooling system 38 pipe 40 container for receiving the irradiated product 18 particle accelerator 20 particle beam 42 overflow container 22 irradiation window 24 Pressure sensor 44 pipe 26 data bus 46 tank with purge gas 28 control device 30 multi-way valve

Claims (13)

1. A method for producing a radioisotope, comprising:

   irradiating a volume of radioisotope precursor fluid contained in a hermetic cell of a target, using a beam of particles of given current intensity which is produced by a particle accelerator;

   cooling the said target; and

   measuring the internal pressure inside said hermetic cell;

   characterized in that:

   the internal pressure (P) inside the said hermetic cell is allowed to be freely established during the said irradiation; and

   the said irradiation is interrupted or its intensity reduced when the internal pressure (P) in said hermetic cell moves out of a first tolerance range determined as a function of different parameters having an influence on changes in internal pressure inside the hermetic cell during irradiation, the said parameters for a given target, given beam of particles and given radioisotope precursor fluid, comprising the extent of filling of the said hermetic cell, the cooling power of the target and the beam current intensity (I).
2. The method according to claim 1 wherein:

   a curve P = f(I) is defined giving the internal pressure (P) of the hermetic cell at different beam current intensities (I), for a given volume of radioisotope precursor fluid and a given cooling power of the said target;

   the said first tolerance range has a lower pressure and an upper pressure limit defined for the said given beam current intensity (I) based on the said curve P = f(I);

   the said lower limit of internal pressure is defined so that it is lower, preferably between 5 % and 20 % lower, that the pressure value inferred from the said curve P = f(I) for the said given beam current intensity (I); and

   the said upper limit of internal pressure is a pressure between the pressure value inferred from the said curve P = f(I) for said given beam current intensity and a nominal pressure value (Pmax) of said hermetic cell, the said nominal pressure value (Pmax) being assumed to represent the maximum pressure value at which the said hermetic cell is guaranteed.
3. The method according to claim 2 wherein the said upper limit of internal pressure in the said first tolerance range is lower by at least 20 % than the said nominal pressure value (Pmax) of the said hermetic cell.
4. The method according to claim 2 or 3 wherein the said upper limit of internal pressure in the said first tolerance range is between 5 and 10 bars higher than the pressure value inferred from the said curve P = f(I) for the said given beam current intensity (I) and its ceiling is a pressure value (P2) that is lower than the said nominal pressure value (Pmax) of the said hermetic cell.
5. The method according to any of the preceding claims wherein a control device triggers an alarm when the internal pressure (P) in the said hermetic cell moves out of a second tolerance range defined as a function of different parameters having an influence on changes in internal pressure in the hermetic cell during irradiation, the said second tolerance range being included within the said first tolerance range.
6. The method according to claim 5 wherein:

   a curve P = f(I) is determined giving the internal pressure (P) of the hermetic cell at different beam current intensities (I), for a given volume of radioisotope precursor fluid and given cooling power of the said target;

   the said first tolerance range has a lower pressure limit and upper pressure limit defined for the said given beam current intensity (I) on the basis of the said curve P = f(I);

   the said second tolerance range has a lower pressure limit and a higher pressure limit defined on the basis of the said curve P = f(I);

   the said lower limit of internal pressure in the said second tolerance range is defined so that it is lower, preferably by at least 2 %, than the pressure value inferred from the said curve P = f(I) for the given beam current intensity (I) whilst remaining higher than the said lower limit of internal pressure in the said first tolerance range; and

   the said upper limit of internal pressure in the said second tolerance range is defined so that it is higher than the pressure value inferred from the said curve P = f(I) for the given beam current intensity (I) whilst remaining lower than the said upper limit of internal pressure in the said first tolerance range.
7. The method according to any of the preceding claims wherein, when the internal pressure (P) in said hermetic cell exceeds an upper limit of internal pressure fixed inside the said first tolerance range, the beam current is decreased.
8. The method according to any of the preceding claims wherein the extent of filling of the hermetic cell is optimised experimentally for a range of envisaged beam currents.
9. The method according to any of the preceding claims wherein the said radioisotope precursor is a precursor of ¹¹C, ¹³N, ¹⁵O or ¹⁸F.
10. An installation for implementing the method according to any of the preceding claims, comprising:

    a target with a hermetic cell capable of containing a volume of precursor fluid, the said hermetic cell being guaranteed to withstand a nominal pressure (Pmax);

    a particle accelerator capable of producing and directing a beam of accelerated particles of a given current intensity (I) onto the said target;

    a system to monitor the internal pressure of the said hermetic cell;

    characterized in that it comprises a control device programmed to interrupt the said beam of particles when the internal pressure (P) inside the said hermetic cell moves out of a first tolerance range determined as a function of different parameters having an influence on changes in internal pressure in the hermetic cell during irradiation.
11. The installation according to claim 10 wherein the said control device is programmed to trigger an alarm when the internal pressure in the said hermetic lies outside a second range included within the said first tolerance range.
12. The installation according to claim 10 or 11 wherein the said control device is programmed to cause a reduction in the intensity of the beam current when the internal pressure (P) in the said hermetic cell exceeds an upper limit of internal pressure included in the said second range.
13. The installation according to any of claims 10 to 12 wherein the said control device is programmed with a curve P = f(I) giving the internal pressure (P) of the hermetic cell at different beam current intensities (I), for a given volume of radioisotope precursor fluid and a given cooling power of the said target, the said curve P = f(I) being used by the said control device to define the said first tolerance range as a function of beam current intensity (I).

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