Patent Grant
9922743
This application is a national phase application of International Application No. PCT/EP2011/068876, filed Oct. 27, 2011, designating the United States and claiming priority to Belgium Patent Application No. 2010/0640, filed Oct. 27, 2010, both of which are incorporated by reference as if fully rewritten herein.
The present invention generally relates to a device for producing radioisotopes, and more particularly a device for producing radioisotopes through radiation using a particle beam of a target fluid comprising a radioisotope precursor. It also relates to an irradiation cell designed to produce radioisotopes through irradiation using a particle beam of a target fluid comprising a radioisotope precursor.
In nuclear medicine, positron emission tomography is an imaging technique requiring radioisotopes imaging positrons or molecules marked by those same radioisotopes. 18F is one of the most commonly used radioisotopes from among others such as 13N, 15O or 11C. 18F has a half-life time of 109.6 min. and can thus be conveyed toward sites other than its production site.
18F is most often produced in its ionic form and obtained by accelerated proton bombardment on an irradiation cell comprising 18O-enriched water. Many irradiation cells have been developed that all have the same purpose of producing 18F in a shorter period of time with a better yield. Generally, the production of radioisotopes comprises a proton accelerator and an irradiation cell. This irradiation cell comprises a cavity, inside which the radioisotope precursor in liquid form is included.
Generally, the energy from the proton beam directed on the irradiation cell is approximately from several MeV to approximately 20 MeV. Such a beam energy causes heating of the irradiation cell as well as vaporization of the radioisotope precursor, thereby decreasing the stopping power of that precursor and therefore the radioisotope production yield. A device cooling the target must therefore also be used so as to try to keep the radioisotope precursor in liquid form, or at most in an intermediate state between liquid and vapor. Furthermore, in the case of 18F production, due to the particularly high cost of the precursor, 18O-enriched water, only a very small volume of that precursor, at most several milliliters, can be placed in the irradiation cell. Consequently, the issue of heat dissipation produced by the irradiation of the target material on such a small volume is a major problem to be overcome. Typically, the power to be dissipated for an energy beam of 18 MeV with an intensity from 50 to 100 μA is between 900 W and 2,700 W, over a radioisotope precursor volume generally comprised between 0.2 and 5 ml, for irradiation times from several minutes to several hours.
Document U.S. Pat. No. 5,917,874 describes a radioisotope production device comprising an irradiation cell closed by a metal foil and comprising a fluid comprising a radioisotope precursor or target fluid. The depth of the cavity of the irradiation cell with respect to the axis of the beam is relatively small so as to irradiate substantially the entire target fluid sample. In one preferred usage example of that document, the depth of the cavity of the irradiation cell is 1.7 mm, so as to have an optimal working cross-section to produce radioisotopes. The energy from the particle beam irradiating the target fluid is approximately 8 MeV, which requires a thin enough metal foil to limit energy losses of the beam when the latter passes through the foil. In the cited document, the foil has a thickness of approximately 6 microns and is held by a perforated grid so as to bear the increasing internal pressure in the irradiation cell during irradiation. The radioisotope production device also comprises means for cooling the irradiation cell. The irradiation cell can be inserted into a cooling housing in which a stream of water circulates. The irradiation cell also comprises a solid column made from a material with a high heat conductivity and situated on the rear side of the irradiation cell, across from the foil, so as to evacuate the heat produced in the cavity. The inside of the cooling housing is cylindrical and comprises a conduit situated across from the apex of said cone and designed to project a turbulent flow of cold water on the cone. The cone also has fins spaced radially around the surface thereof, so as to improve the evacuation of the heat. Such a device only enables the irradiation of small volumes of 18O-enriched water, and does not have the means making it possible to effectively cool the metal foil, which can be problematic in terms of the sealing of the irradiation cell. Furthermore, the perforated grid is not completely transparent to the beam and prevents part of the beam from penetrating inside the cavity. Part of the perforated grid or the metal foil therefore absorbs part of the beam, which causes heating of the metal foil. The metal foil being relatively thin and being the most heated and least well-cooled part, it is relatively fragile. Furthermore, the seals situated between the latter and the body are damaged during use and said cavity loses sealing.
Document BE 1011263 describes a radioisotope production device comprising an irradiation cell with a cavity comprising a hemispherical part, closed by a foil. The irradiation cell receives a fluid comprising a radioisotope precursor also called “target fluid.” The walls of this cavity are made from a heat-conducting metal material and with a thin enough thickness to dissipate the heat from the inside of the cavity. An element called a “diffuser” surrounds the outer walls of said cavity, creating a channel in which a coolant circulates. Nevertheless, the irradiation cell must have a minimal depth so as to sufficiently irradiate target fluid without beam losses in the body of the irradiation cell. In order to increase the depth of the cavity without significantly increasing the volume of the cell so as to minimize the quantity of 18O inside the cell, an irradiation cell as described in document WO 2005081263 has been produced. This irradiation cell comprises a first cylindrical part and a second hemispherical part situated on the side opposite a foil closing the cavity. A first drawback of this type of device is that when the irradiation cell is irradiated, a large portion of the fluid comprised in the cavity vaporizes, leaving only a thin net of water on the lower wall of the cavity. The particle beam passing through a low-density volume, the likelihoods of 18O(p,n)18F nuclear reactions are decreased. Furthermore, the walls of the cavity being relatively thin and undergoing significant heating, said cavity collapses after several uses, which positions part of the liquid, which is already not very irradiated, outside the beam and causes a drop in yield.
Document US 20050084055 describes a radioisotope production device comprising an irradiation cell comprising a target fluid. The irradiation cell comprises a cavity closed by a foil. The cavity comprises a face opposite said foil and called “rear wall,” as well as an upper wall situated at the top of the foil and the rear wall. The rear wall is inclined such that the part of the rear wall proximal to the upper wall is further from the foil than the part of the rear wall distal to the upper wall. The device also comprises a cooling system comprising a vertical conduit 502 through which a coolant arrives. The vertical conduit 502 is connected to a conduit 504 and adjacent to the rear wall, which in turn is connected to a conduit 506 adjacent the upper wall. In this device, the lower wall separating said surface from the part of the rear wall distal to the upper wall is not cooled. Furthermore, the cooled walls are only cooled by a conduit in contact with part of the walls. Lastly, the fluid present in the cavity condenses on the cooled upper wall through a liquid having been heated after having passed through the conduit 504 and adjacent to the rear wall. The cooling of the fluid comprised in the cavity is therefore not optimal and must be improved so as to have more condensed liquid across from the beam so as to increase the probabilities of nuclear reactions.
With the aim of reducing the mechanical stresses on the foil due to the increase in pressure in the cavity during irradiation, document U.S. Pat. No. 6,586,747 describes a radioisotope production device comprising an irradiation cell comprising a cavity closed by a foil that is inclined relative to the axis of the beam. In this way, the power of the beam is distributed over a larger area. Nevertheless, in this device, with the increase in the area of the foil exposed to the beam, the power of the beam dissipated in the foil nevertheless remains high, which causes overall heating of the foil and an increase in the inner pressure in the cavity.
Document US 20060062342 aims to resolve the problem of pressure stresses on the foil by introducing a pressurized chamber adjacent to the foil of the irradiation cell, such that the pressure exerted on the foil on the side of the pressurization chamber opposes the pressure exerted on the same foil on the side of the irradiation cell. The incline or perpendicular position relative to the beam of the target chamber foil should make it possible to force the target fluid under the apex of the foil. Nevertheless, the device does not comprise a system for cooling the foil, and the addition of a pressurized chamber and therefore additional foil in the passage of the beam causes power losses of the beam. The foil being poorly cooled, it is difficult to force the fluid against the apex of said foil.
The document FIROUZBAKHT M. L. et al, “Mechanism of nitrogen-13-labeled ammonia formation in a cryogenic water target—Target design, products and operating parameters,” Nuclear Medicine and Biology, ELSEVIER, N.Y. vol. 26, no. 4, May 1, 1999, pages 437-441, describes a target with a conical cavity cooled by a cryogenic liquid. The foil forming the irradiation window is separated from the conical cavity by an annular channel that serves to collect, through gravity, at the lowest level, the liquid the condenses on the walls of the cavity.
The document FIROUZBAKHT M. L. et al, “Cryogenic target design considerations for the production of [18F]fluoride from enriched [18O] carbon dioxide,” Nuclear Medicine and Biology, ELSEVIER, N.Y., vol. 26, no. 7, Oct. 1, 1999, pages 749-753, also describes targets cooled by a cryogenic liquid. The cavity of the target of
It will be noted that cryogenic cooling targets cause fewer problems regarding cooling of the cell and the metal foil forming the irradiation window. They do, however, require finding gaskets that withstand cryogenic temperatures and, at the same time, have a sufficient lifetime when exposed to intense irradiation.
In order to increase the radioisotope production yields, it is necessary to provide a radioisotope production device that does not comprise the drawbacks of the prior art.
In particular, it is necessary to provide effective means for cooling the window closing the target cavity, particularly when working with a non-cryogenic coolant.
It is also necessary to improve the cooling device for the walls of the target cavity.
Other advantages and properties of the device according to the invention will be shown in light of the following description.
According to a first aspect, the present invention relates to a device designed to produce radioisotopes through the irradiation of a target fluid comprising a radioisotope precursor using a particle beam, the device comprising:
Preferably, the metal foil is positioned substantially perpendicular to the axis of the particle beam.
Preferably, the radioisotopes are produced by irradiating a target fluid using a substantially horizontal particle beam. Preferably, the plane formed by the metal foil is a vertical plane.
Preferably, the acute angle (α) is comprised between (approximately) 30° and (approximately) 89°, preferably between (approximately) 45° and (approximately) 85°, still more preferably between (approximately) 60° and (approximately) 85°.
Preferably, the cooling device comprises a coolant intake situated across from the part of the irradiation cell opposite said foil, and a diffuser creating a channel capable of circulating the coolant.
The inclined surface may for example be a plane or surface made up of several planes or a curved surface or surface made up of several curved surfaces. Preferably, the cavity has a substantially conical shape, and preferably over the largest part of its depth, is in the form of a straight cone of revolution. In this embodiment, the inclined surface is then a concave surface of a cone, and the corner-shaped area is defined by a cone surface, the plane formed by the metal foil, and a horizontal plane intercepting the cone surface and the plane formed by the metal foil.
Preferably, the apex of the substantially conical cavity is rounded, and is preferably in the form of the spherical cap.
Preferably, the irradiation cell comprises:
Preferably, the first part further comprises a groove surrounding the second part on the side of the rear surface, said groove being designed to serve as a collector for a coolant flowing along the outer surface of said second part.
Preferably, the irradiation cell is made from niobium.
Preferably, the outer surface of the second substantially conical part comprises furrows, preferably extending from an area close to the apex of the second part toward a region close to the base of the second part, so as to create pathways for the passage of said coolant flowing along the outer surface of said second part.
According to another aspect, the present invention relates to an irradiation cell designed to produce radioisotopes by irradiating a target fluid comprising a radioisotope precursor using a particle beam, the cell comprising:
Preferably, the first part also comprises a groove, which, on the side of the rear surface, surrounds the outer surface of the second part, so as to reduce the thickness of the first part at the base of the second part, said groove being designed to serve as a collector for a coolant flowing along the outer surface of the second part.
Preferably, the outer surface of the second substantially conical part comprises furrows, each of said furrows preferably extending from an area close to the apex of the second, substantially conical part toward a region near the base of the second part, so as to create pathways between them for the passage of a coolant flowing along the outer surface of the second part.
The device according to the present invention is designed to be used in the context of radioisotope production, in particular through irradiation of a target fluid using an accelerated particle beam. One preferred use of the device 1 according to the present invention is the production of 18F through bombardment using an accelerated proton beam 13 on 18O-enriched water. Preferably, the beam 13 is substantially horizontal.
The irradiation cell 7 can be inserted into a body 8 comprising a cooling device. The cooling device comprises a coolant inlet 9, preferably a non-cryogenic coolant. The coolant intake 9 is preferably situated along the axis A-B and oriented toward the part of the irradiation cell 7 opposite the foil 4. Preferably, the cooling device also comprises a diffuser 14 creating an annular channel 10 around the irradiation cell 7. The coolant circulating in the channel 10 must ensure that the walls of the irradiation cell 7 are cooled enough for the target fluid comprised in the cavity 3 to remain essentially in liquid form.
The cavity 3 comprises, in the lower part 20 thereof, an inclined surface 15 (here a concave conical surface, since the cavity 3 is preferably substantially conical). This inclined surface 15 delimits the lower part 20 of the cavity at the bottom thereof, so as to evacuate the target fluid, which condenses in contact with the cold walls of the cavity 3 by gravity toward said metal foil 4. It intercepts the plane formed by the metal foil 4 by forming an acute angle (α) with that plane, so as to form an area 18 capable of receiving, by gravity, the coolant that (during operation) condenses in contact with the walls of the cavity 3 cooled by the cooling device. Preferably, the acute angle (α) is comprised between 30° and 89°, more preferably between 45° and 85°, and still more preferably between 60° and 85°. The inclined surface 15 is in contact with the lower part of the metal foil 4, thereby creating the area 18 of the cavity 3 in contact with the metal foil 4 in which target fluid condensed on the walls of the cavity 3 may accumulate more quickly.
According to one preferred aspect, the cavity 3 is substantially conical. The conical shape of the cavity makes it possible to maximize the cooled surface Sr relative to the volume of the cavity Vc. It has in fact surprisingly been discovered that if the Sr/Vc ratios are compared to the shapes of the cavities of the prior art with that of the present invention, it can be seen that for a given opening radius of the cavity R and depth of the cavity P (
Tables 1, 2 and 3 show that for a same depth P of the cavity and a same opening radius R of the cavity, the volume of a conical irradiation cell is always smaller than the volume of an irradiation cell comprising a cylindrical part and a hemispherical part as described in document WO 2005081263. Consequently, for a same depth P of the cavity and a same opening radius R of the cavity, the “area of the cooled surface per unit of volume” ratio Sr/Vc for a conical irradiation cell is always larger than that of an irradiation cell as described in document WO 2005081263. Advantageously, the irradiation cell 7 for use in the device 1 according to the present invention therefore enables the irradiation of a reduced target fluid volume, while keeping the depth of the cavity 3 sufficient to prevent beam losses, and providing improved cooling.
According to another preferred aspect, the irradiation cell is made from niobium, a material chosen for its chemical inertia properties and acceptable thermal properties. Niobium does not produce secondary radioisotopes whereof the half-life time exceeds 24 hours. Niobium nevertheless has the drawback of being difficult to machine, which is why in this preferred aspect, the apex of the cell is preferably rounded.
One example embodiment of an irradiation cell made from niobium is shown in
According to another preferred aspect, the radius R of the opening of the cavity is comprised between 2 mm and 20 mm, more preferably between 5 mm and 15 mm, and the depth of the cavity is preferably comprised between 1 and 10 cm, more preferably between 1 cm and 5 cm.
According to another preferred aspect, the height h2 of the spherical cap is less than 1 cm.
An irradiation cell 7 according to one preferred aspect is shown in
The conical cavity 3 passes through the first part 16 to extend into the second part 17, and forms, in the front surface of the first part 16, an opening delimited by the edge 22, with a circular shape, such that said metal foil 4 closes the opening at the edge 22 when it bears on the front surface of the first part 16.
According to another preferred aspect of the present invention, the outer surface of the second part 17 of the irradiation cell 7 comprises linear furrows 12, each of said furrows 12 preferably extending from a region/area close to the apex of the second substantially conical part 17 toward a region near the base of the second substantially conical part 17, so as to create pathways between them making it possible to accelerate the passage of the coolant 9 and therefore to improve cooling. The addition of the furrows 12 also causes an increase in the outer surface area of the cone and therefore the heat exchange surface area.
According to still another preferred aspect, the first part 16 of the irradiation cell 7 also comprises an annular groove 11 surrounding the second part 17, at the base of the second, substantially conical part 17, locally reducing the thickness of the first part 16 of the irradiation cell 7.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2010/0640 | Oct 2010 | BE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2011/068876 | 10/27/2011 | WO | 00 | 6/12/2013 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2012/055970 | 5/3/2012 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 5917874 | Schlyer | Jun 1999 | A |
| 6586747 | Erdman | Jul 2003 | B1 |
| 8288736 | Amelia | Oct 2012 | B2 |
| 20050084055 | Alvord et al. | Apr 2005 | A1 |
| 20060062342 | Gonzalez Lepera et al. | Mar 2006 | A1 |
| 20060104401 | Jongen | May 2006 | A1 |
| Number | Date | Country |
|---|---|---|
| 1011263 | Jun 1999 | BE |
| 1569243 | Aug 2005 | EP |
| 2005081263 | Sep 2005 | WO |
| Entry |
|---|
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| International Search Report, International Patent Application No. PCT/EP2011/068876, date of completion Nov. 30, 2011, 3 pages. |
| Mahmoud L. Firouzbakht et al., “Mechanism of Nitrogen-13-Labeled Ammonia Formation in a Cryogenic Water Target.” Nuclear Medicine & Biology, 1999, vol. 26, pp. 437-441. |
| Mahmoud L. Firouzbakht et al., “Cryogenic Target Design Considerations for the Production of [18F]Fluoride From Enriched [18O]Carbon Dioxide.” Nuclear Medicine & Biology, 1999, vol. 26, pp. 749-753. |
| T. Kakavand et al., “Computer Simulation Techniques to Design Xenon-124 Solid Target for Iodine-123 Production.” Iran. J. Radiat. Res., 2008; vol. 5, No. 4, pp. 207-212. |
| Number | Date | Country | |
|---|---|---|---|
| 20130266105 A1 | Oct 2013 | US |
