GB2487198A

GB2487198A - Apparatus and methods for the production of mo-99 using a compact neutron generator

Info

Publication number: GB2487198A
Application number: GB201100442A
Authority: GB
Inventors: Timothy John Hughes; Oliver Heid; Paul Beasley
Original assignee: Siemens AG
Current assignee: Siemens AG
Priority date: 2011-01-12
Filing date: 2011-01-12
Publication date: 2012-07-18
Also published as: GB201100442D0

Abstract

The present invention provides apparatus for producing Mo-99, comprising a source of protons 12 (32, 34 fig. 4); DC electrostatic accelerator 10 (30, fig. 4) to accelerate the protons from the source of protons into a proton beam 22 (38, fig. 4); a neutron generator target material 14 (40, fig. 4) which releases a beam of neutrons 16 (42, fig. 4) in response to an incident beam of protons 22 (38, fig. 4); and a target 20 (44, fig. 4), which is hit by the neutron beam (16; 42) and contains a species which becomes Mo-99 in response to the incident neutron beam. The Mo-99 generating material is preferably Mo-98 or U-235 and the neutron generator is preferably Li-7. A corresponding method is also provided. In another embodiment, the neutron beam is produced by applying deuterium ions to a neutron generator target material (for preference Be-10) which releases a beam of neutrons in response to an incident beam of deuterium ions. In a further embodiment, Mo-99 is generated by applying a proton beam to Mo-100.

Description

I

APPARATUS AND METHODS FOR THE PRODUCTION OF MO-99

USING A COMPACT NEUTRON GENERATOR

As is well known, Nuclear Medicine is currently used in the diagnosis of tumours, and investigations into other medical conditions.

Technetium Tc99m is an important radioisotope used in Nuclear Medicine.

Currently, it is produced in a two-part process. The first part of the process involves the production of Molybdenum Mo-99. The Mo-99 produced then decays to Tc-99m with a half life of 66 hours.

Typically, the Mo-99 is produced in a high flux nuclear reactor using HEU (highly enriched Uranium).

Conventionally, a Tc99m generator is a device used to extract the metastable isotope Tc-99m of technetium from a source of decaying molybdenum Mo-99 at the point of use. Mo-99 has a half-life of 66 hours and can be easily transported over long distances to hospitals, whereas its decay product technetium Tc99m is extracted and used for a variety of nuclear medicine diagnostic procedures. Technetium Tc99m has a half-life of only 6 hours, which is inconvenient for transport, but is useful in medical diagnostic procedures.

Conventional Mo-99 / Tc99m generators use column chromatography, in which Mo- 99 in the form of molybdate, MoO42 is adsorbed onto acid alumina (AI2O3). When the Mo-99 decays, it forms pertechnetate Tc04, which because of its single charge is less tightly bound to the alumina. Pulling normal saline solution through the column of immobilized Mo-99 elutes the soluble Tc-99m, resulting in a saline solution containing the Tc99m as the pertechnetate, with sodium as the counterbalancing cation.

The solution of sodium pertechnetate may then be added in an appropriate concentration to a pharmaceutical to be used, or sodium pertechnetate can be used directly without pharmaceutical tagging for specific procedures requiring only the Tc- 990 as the primary radiopharmaceutical.

A large percentage of the Tc-99m generated by a Mo-99ITc-99m generator is produced in the first 3 parent half lives, or approximately one week. Hence, clinical nuclear medicine units purchase at least one such generator per week, or order several in a staggered fashion.

There has been considerable disruption to the Mo-99 supply chain due to the small number of reactors in the world: recently estimated at five, and their lengthy maintenance schedules due to their age and safety concerns of operating a nuclear reactor.

The present invention accordingly proposes alternative methods and apparatus for producing Mo-99, both as a product in itself, and as an intermediate product in a method of producing Tc99m, which methods and apparatus do not require the use of a high flux nuclear reactor and I-IEU.

The present invention accordingly proposes methods and apparatus as defined in the appended claims.

The above, and further, objects, characteristics and advantages of the present invention will become more apparent from consideration of the following description of certain embodiments thereof, together with the accompanying drawings, wherein: Fig. I schematically illustrates a DC accelerator useful in a method according to a first embodiment of the invention; Fig. 2 schematically illustrates apparatus for producing Mo-99 according to the first embodiment of the present invention; and Fig. 3 schematically illustrates a tandem DC accelerator useful in a method according to a second embodiment of the invention; Fig. 4 schematically illustrates apparatus for producing Mo-99 according to the second embodiment of the present invention.

The present invention provides methods and apparatus for producing Mo-99 using a DC electrostatic accelerator.

The attached appendix, which forms part of the present description, describes high-voltage electrostatic accelerators which may be employed in the methods of the present invention, and may form part of the apparatus according to the present invention. As described, high voltage accelerators may be provided as tandem accelerators or conventional linear accelerators.

In a conventional linear accelerator, a target is placed in the centre of the accelerator and charged particles are directed towards that target. The charged particles interact with the target.

Fig. I shows such a conventional linear accelerator. A target 100 is positioned in a central region 101 of the accelerator. The accelerator itself is made up of concentric shells 102, split at an "equator" 103 such that each shall is made up of two half-shells, separated by a gap. A path 104 is provided, perpendicular to the "equator" and leading in a straight line to the target from outside of the accelerator. A beam of charged particles may be directed along the path 104 to the target 100. Each shell is charged to a high voltage as compared to its outwardly neighbouring shell, and the description in the appendix recites one possible arrangement for achieving this. In the described example, thirty concentric shells are used, charged up by a I 00kVe, 100kHz AC inverter. This provides a voltage of 5MV at the centre, and a voltage gradient of 5MV/(30x15mm) = 11.11kV/mm. By charging the shells with a voltage of polarity opposite to that of the charged particles, the beam 105 of charged particles is accelerated towards the centre of the accelerator. The beam 105 of particles hits target 100 and undergoes the required reaction.

In a tandem accelerator, a particle converter is placed in the centre of the accelerator and charged particles are directed towards that particle converter. The charged particles interact with the particle converter, and emerge as a different type of charged particle, in the same trajectory as the original charged particle. Assuming that the different type of particle has the opposite charge as compared to the original particle, it will be accelerated out of the accelerator, while the original particle is accelerated into the accelerator.

Fig. 3 shows such a tandem accelerator. This shares features common with those of the accelerator in Fig. I, sharing common reference numerals. A particle converter is positioned in the central region 101 of the accelerator. The accelerator itself is made up of concentric shells 102, split at an "equator" 103 such that each shell is made up of two half-shells, separated by a gap. A first path 104 is provided) perpendicular to the "equator" and leading in a straight line to the particle converter from outside of the accelerator. A second path 204 is provided) in line with the first path 104 and leading in a straight line from the particle converter to outside of the accelerator.

A beam 105 of charged particles may be directed along the path 104 to the particle converter 200. Each shell is charged to a high voltage as compared to its outwardly neighbouring shell, and the description in the appendix recites one possible arrangement for achieving this. In the described example) thirty concentric shells are used) charged up by a 1 OOkVen, 100kHz AC inverter. This provides a voltage of 5MV at the centre) and a voltage gradient of 5MV/(30x15mm) = 11.11kV/mm. By charging the shells with a voltage of polarity opposite to that of the charged particles) the beam of charged particles is accelerated towards the centre of the accelerator.

When the charged particles hit the particle converter) they are converted into different particles, with an opposite charge. For example) ft ions may hit a particle converter being an ion stripper arrangement) conventional in itself) and be converted to i( ions, protons.

The oppositely-charged particles are then repelled from the centre of the accelerator) accelerating out along path 204. A target 210 is positioned outside of the accelerator. The oppositely-charged particles leave the accelerator and hit target 210. The beam 105 of particles hits target 100 and causes emission of other particles.

The present invention may be applied both to conventional linear accelerators and tandem accelerators. Various different targets may be used, as will be described in more detail in the following examples.

According to a first example of the first embodiment of the invention, Mo-99 may be produced using a compact neutron generator through a Mo-98(n,-y)Mo-99 route.

According to this embodiment of the invention, and as schematically represented in Fig. 1, a conventional linear DC electrostatic accelerator 10, similar to that described with reference to Fig. 1, is provided with a beam 22 of protons (H ions) from a proton source 12. In the centre of the DC electrostatic accelerator is a target of neutron source material 14, such as a thin Lithium Li-7 target, which produces neutrons 16 from the (p,n) reaction Li-7(p,n)Be-8 or similar.

The Li-i reaction is particularly advantageous because it is a transition reaction which, at around 1.885MeV, produces a collimated neutron beam 16. Depending on their required energy the collimated neutron beam 16 can be directed at a moderator 18 to produce an epithermal neutron spectrum (a neutron that has energy about that of a thermal neutron, but not as large as for fast neutrons, so having a modest requirement for shielding).

After the moderator 18, the neutrons hit a target 20 including Mo-98. This interaction results in the production of Mo-99 through an Mo-98(n,y)Mo-99 reaction.

In an example DC electrostatic accelerator, the H ions are accelerated to the centre of the accelerator, at which point they cross the centre into the shell structure of the accelerator on the opposite side, which has a decelerating field.

The incident proton beam 22 loses a portion of its energy as it passes through the neutron-source material 14. As the resulting proton beam 24 exits the target, it is gradually slowed as it passes through the accelerator 10 and is collected in the structure of the DC electrostatic accelerator, acting as a collector assembly. In this way, the energy of the beam is recovered.

In a second example of the first embodiment of the invention, similar to the first example, the proton source 12 is replaced with a source of deuterium ions 2H' (D).

The neutrons are generated as a result of accelerated particles of deuterium l-l (D) hitting a target 14 of beryllium Be-b in a Be-b0(d,n)C-11 reaction to produce carbon- 11 and a free neutron.

The free neutron may then be directed towards the Mo-98 target 20 to produce Mo-99 in an Mo-98(n, y) reaction.

In a third example of this first embodiment, apparatus and methods are provided for producing Mo-99 using a compact neutron generator for the production of Mo-99 through the U-235 fission route with an energy recycling proton beam. As in the first or second examples, at the centre of the DC electrostatic accelerator 10 is a material 14 which produces neutron beams 16 in response to the incident proton beam 22.

The collimated neutron beam 16 is directed at a moderator 18, which produces an epithermal neutron spectrum.

In this example, after the moderator 18, the neutrons hit a subcritical Uranium U-235 target 20 to produce U-236 through the U-235(n,y)U-236 reaction. The U-236 fissions to become Mo-99 plus other fission products and neutrons. Mo-99 may then be separated from other fission products in a hot cell.

The resulting Mo-99 is removed from the U-235 target 20 by a chemical process which is conventional in itself.

The incident proton beam 22 loses a portion of its energy in the target 14. As the proton beam exits the target as shown at 24, it is gradually slowed as it passes through the accelerator and is collected in the structure of the DC electrostatic generator. In this way, the energy of the beam is recovered.

In further examples of the first embodiment, Mo-99 is produced by conversion of Mo- 100. A proton beam is generated, for example by any of the methods described in the publication "Ion and Electron Sources" by C.E. Hill and published by CERN. A copy of that paper is filed with the present application. The proton beam is them aimed at a target containing Mo-100. This is converted to Mo-99 by a Mo-I 00(p,pn)Mo-99 reaction.

According to a second embodiment of the invention, alternative apparatus and methods are provided for producing Mo-99 using a tandem compact neutron generator, through a Mo-98(n,y)Mo-99 reaction route.

Fig. 4 schematically represents an example of apparatus according to second embodiment of the present invention, using a tandem DC electrostatic accelerator.

According to a first example of this second embodiment of the invention, a tandem DC electrostatic compact accelerator 30, similar to that described with reference to Fig. 2, is provided with a source 32 of ft ions, and produces a beam 36 of ft ions directed towards the centre of the accelerator. In the centre of the tandem DC electrostatic accelerator 30 is an ion stripper arrangement 34 (such as a carbon stripper foil which is conventional in itself), which converts ft ions to H4 ions (protons) by removal of two electrons from each ion. The resulting H beam 38 is incident upon a target material 40 which produces neutron beams 42 in reaction to the incident protons. For example, the material 40 may be Lithium Li-7, which produces neutron beams 42 from the (p,n) reaction Li-7(p,n)Be-8, or another material with a similar reaction to incident protons. Conventional ion stripper arrangements are described, for example, in Proceedings of EPACO8, Genoa, Italy pp3620-3622 04 T12 A. Takagi et aL "Temperature Measurement of Carbon Stripper Foil by Pulsed 65OkeV I-I-ion beam' and the 2002 publication by T. Spickermann et al. "Comparison of Carbon Stripper Foils Under Operational Conditions at the Los A/amos Proton Storage Ring" Copies of these papers are filed with the present application.

This Li-7(p,n)Be-8 reaction is particularly advantageous because it is a transition reaction which, at around 1.885MeV, produces a collimated neutron beam 42. The collimated neutron beam 42 is directed at a moderator (not shown in the drawing, but could be a simple water vessel or wax block) to produce an epithermal neutron spectrum. After the moderator, the neutrons hit a Mo-98 target 44, producing Mo-99 through the Mo-98(n,y)Mo-99 reaction.

In a second example of this second embodiment, apparatus and methods are provided for producing Mo-99 using a compact neutron generator for the production of Mo-99 through the U-235 fission route with an energy recycling proton beam. As in the first example, at the centre of the DC electrostatic accelerator 10 is an ion stripper arrangement 34 which produces a proton beams 38 in response to the incident ft ions 36.

The proton beam is directed to target 40, which produces neutron beams 42 in reaction to the incident protons. The target 40 may be of Li-7 as described above.

The resulting Mo-99 is removed from the U-235 by a chemical process which is conventional in itself.

In a further example of the second embodiment, Mo-99 is produced by conversion of Mo-I 00. A proton beam 38 is generated by the method described in relation to the first and second examples. The proton beam 38 is them aimed at target 44 containing Mo-100. This is converted to Mo-99 by a Mo-I 00(p,pn)Mo-99 reaction. In this example, there is no need for the first target 40, but the proton beam 38 is directed onto the Mo-i 00 target 44.

Accordingly, the present invention provides methods an apparatus for the production of Molybdenum Mo-99 which is of use, for example, in the preparation of Technetium Tc99m for use in Nuclear Medicine.

Such a system has the advantage of enabling the on-site production of Mo-99.

According to the present invention, neutron beams are produced in-situ from readily generated l-I or H ion beams. This avoids the conventional requirement for a neutron source, which is usually a large piece of equipment, a particle accelerator or a reactor.

The appended annex contains detailed descriptions of certain types of DC electrostatic accelerator, which are considered suitable for use in the present invention.

Numerous variations and modifications to the present invention will be apparent to those skilled in the art, and the scope of the invention is as defined in the appended claims. For example, while certain arrangements have been described for producing neutrons from a proton beam, any suitable known or later-devised combination or particles or target material may be employed in the present invention.

Claims

CLAIMS1. Apparatus for producing Mo-99 comprising: -a source of protons (12; 32, 34); -a DC electrostatic accelerator (10; 30) to accelerate the protons from the source of protons into a proton beam (22; 38); -a neutron generator target material (14; 40) which releases a beam of neutrons (16; 42) in response to an incident beam of protons (22; 38); and -a target (20; 44), which is hit by the neutron beam (16; 42) and contains a species which becomes Mo-99 in response to the incident neutron beam.
2. Apparatus according to claim 1 wherein the target contains Mo-98.
3. Apparatus according to claim 1 wherein the target contains U-235.
4. Apparatus according to any preceding claim wherein the neutron generator target material comprises lithium Li-7.
5. Apparatus according to any preceding claim, further comprising a moderator (18) to reduce the energy of neutrons in the neutron beam before they hit the target.
6. Apparatus according to claim 5, wherein the neutron generator target material (14) is at the centre of the DC electrostatic accelerator.
7. Apparatus according to any preceding claim, wherein the DC electrostatic accelerator is a DC electrostatic compact accelerator (30).
8. Apparatus according to any preceding claim, wherein the source of protons itself comprises: -a source (32) of H ions and -an ion stripper arrangement (34) at the centre of the accelerator, such that H ions from the H ion source accelerate into the accelerator (30) and impact upon the ion stripper arrangement (34) arranged to convert the ft ion beam (36) to a proton beam (38).
9. Apparatus according to claim 5, wherein the DC electrostatic accelerator is a tandem DC electrostatic compact accelerator.
10. Apparatus according to any preceding claim, further comprising a collector assembly in the DC electrostatic accelerator (10), arranged to catch and recycle proton beam energy.
11. A method for producing Mo-99 comprising the steps of: -generating protons (12; 32, 34); -accelerating the protons into a DC electrostatic accelerator (10; 30) to form a proton beam (22; 38); -applying the proton beam to a neutron generator target material (14; 40) which releases a beam of neutrons (16; 42) in response to the incident beam of protons (22; 38); -applying the beam of neutrons to a target (20; 44), which contains a species which becomes Mo-99 in response to the incident neutron beam.
12. A method according to claim 11 wherein the target contains Mo-98.
13. A method according to claim 11 wherein the target contains U-235.
14. A method according to claim 11, further comprising the step of reducing the energy of neutrons in the neutron beam before they hit the target by passing the beam of neutrons through a moderator (18).
15. A method according to any of claims 11-14 wherein the step of generating protons itself comprises the steps of: -generating ft ions -accelerating the ft ions into the accelerator to form a beam of I-f ions; -stripping electrons from the F-f ion beam (36) to generate a proton beam (38).
16. A method according to any of claims 11-15 further comprising catching and recycling proton beam energy by collecting protons in a collector assembly in the DC electrostatic accelerator.
17. Apparatus for producing Mo-99 comprising: -a source of deuterium ions D; + -a DC electrostatic accelerator (10; 30) to accelerate the deuterium ions from the source of deuterium ions into a beam of deuterium ions; -a neutron generator target material (14) which releases a beam of neutrons (16) in response to an incident beam of deuterium ions; and -a target (20), which is hit by the neutron beam (16) and contains a species which becomes Mo-99 in response to the incident neutron beam.
18. Apparatus according to claim 17 wherein the target contains Mo-98.
19. Apparatus according to claim 17 wherein the target contains U-235.
20. Apparatus according to any of claims 17-19 wherein the neutron generator target material comprises Beryllium Be-I 0.
21. Apparatus according to any of claims 17-20, further comprising a moderator (18) to reduce the energy of neutrons in the neutron beam before they hit the target.
22. Apparatus according to claim 21, wherein the neutron generator target material (14) is at the centre of the DC electrostatic accelerator.
23. Apparatus according to any of claims 17-22, wherein the DC electrostatic accelerator is a DC electrostatic compact accelerator (30).
24. A method for producing Mo-99 comprising the steps of: -generating deuterium ions D; -accelerating the deuterium ions into a DC electrostatic accelerator (10) to form a beam of deuterium ions; -applying the beam of deuterium ions to a neutron generator target material (14) which releases a beam of neutrons (16) in response to the incident beam of deuterium ions; -applying the beam of neutrons to a target (20), which contains a species which becomes Mo-99 in response to the incident neutron beam.
25. A method according to claim 24 wherein the target contains Mo-98.
26. A method according to claim 24 wherein the target contains U-235.
27. A method according to any of claims 24-26, further comprising the step of reducing the energy of neutrons in the neutron beam before they hit the target by passing the beam of neutrons through a moderator (18).
28. A method according to any of claims 24-27 wherein the neutron generator target material comprises Beryllium Be-b.
29. A method according to any of claims 24-28 further comprising catching and recycling proton beam energy by collecting protons in a collector assembly in the DC electrostatic accelerator.
30. Apparatus for producing Mo-99 comprising: -a source of protons; -a DC electrostatic accelerator to accelerate the protons from the source of protons into a proton beam; and -a target, which is hit by the proton beam and contains a species which becomes Mo-99 in response to the incident proton beam.
31. Apparatus according to claim 30 wherein the target contains Mo-100.
32. Apparatus according to claim 30 or claim 31, wherein the target material is at the centre of the DC electrostatic accelerator.
33. Apparatus according to any of claims 30-32, wherein the DC electrostatic accelerator is a DC electrostatic compact accelerator (30).
34. A method for producing Mo-99 comprising the steps of: -generating protons; -accelerating the protons into a DC electrostatic accelerator to form a proton beam; -applying the proton beam to a target, which contains a species which becomes Mo-99 in response to the incident proton beam.
35. A method according to claim 34 wherein the target contains Mo-I 00.