# Patent

## Title
Method and device for producing a 99mTc reaction product

## Abstract

A method for producing a reaction product containing 99mTC may include providing 100Mo-metal targets to be irradiated, irradiating the 100Mo-metal target with a proton stream having an energy for the induction of a 100Mo(p, 2n)99mTC core reaction, heating the 100Mo-metal target to over 300° C., recovering incurred 99mTc in a sublimation-extraction process with the aid of oxygen gas which is conducted over the 100 Mo-metal target forming 99mTc-Technetium oxide. Further, a device for producing the reaction product containing 99mTc may include a 100Mo metal target, an acceleration unit for providing a proton stream, which can be directed to the 100Mo-Metal target, such that a 100Mo(p, 2n)99mTC core reaction is induced upon irradiation of the 100Mo-metal target by the proton stream, a gas supply line for conducting oxygen gas onto the irradiated 100Mo-metal target to form 99mTC-Technetium oxide, and a gas discharge line to discharge the sublimated 99mTC-Technetium oxide.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a U.S. National Stage Application of International Application No. PCT/EP2011/051017 filed Jan. 26, 2011, which designates the United States of America, and claims priority to DE Patent Application No. 10 2010 006 434.3 filed Feb. 1, 2010. The contents of which are hereby incorporated by reference in their entirety.
TECHNICAL FIELD
This disclosure relates to a method and a device for producing a 99mTc reaction product. 99mTc is used in medical imaging in particular, for example in SPECT imaging.
BACKGROUND
A commercially available 99mTc-generator is an instrument for extracting the metastable isotope 99mTc from a source containing decaying 99Mo, for example with the aid of solvent extraction or chromatography.
99Mo in turn is usually obtained from a method which uses highly enriched uranium 235U as a target. 99Mo is created as a fission product by irradiating the target with neutrons. However, as a result of international treaties, it will become ever more difficult in future to operate reactors with highly enriched uranium, which could lead to a bottleneck in the supply of radionuclides for SPECT imaging.
U.S. Pat. No. 5,802,438 discloses a method for producing 99mTc by irradiating a Mo-metal target in the surroundings of a reactor. HU 53668 (A3) and HU 37359 (A2) describe methods in which 99mTc is obtained with the aid of sublimation processes.
SUMMARY
In one embodiment, a method for producing a reaction product containing 99mTc may comprise: providing a 100Mo-metal target to be irradiated, irradiating the 100Mo-metal target with a proton beam having an energy suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction, heating the 100Mo-metal target to a temperature of over 300° C., and obtaining the 99mTc made in the 100Mo-metal target in a sublimation-extraction process with the aid of oxygen gas, which is routed over the 100Mo-metal target forming 99mTc-technetium oxide in the process.
In a further embodiment, the method further comprises feeding the obtained 99mTc-technetium oxide to an alkaline solution, more particularly to a sodium hydroxide solution, or to a salt solution to form 99mTc-pertechnetate. In a further embodiment, the 100Mo-metal target is available in the form of a film, in the form of a powder, in the form of tubules, in the form of a grid structure, in the form of spheres or in the form of metal foam. In a further embodiment, the 100Mo-metal target is held by a thermally insulating mount. In a further embodiment, heating of the 100Mo-metal target is achieved by the irradiation by the proton beam. In a further embodiment, the heating is brought about with the aid of current conducted through the 100Mo-metal target. In a further embodiment, the heating is brought about by heating a chamber, more particularly a ceramic chamber, in which the 100Mo-metal target is arranged.
In another embodiment, a device for producing a reaction product containing 99mTc may comprise: a 100Mo-metal target, an accelerator unit for providing a proton beam which can be directed at the 100Mo-metal target, the proton beam having an energy which is suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction when the 100Mo-metal target is irradiated by the proton beam, a gas supply line for routing oxygen gas onto the irradiated 100Mo-metal target for forming 99mTc-technetium oxide, and a gas discharge line for discharging the sublimated 99mTc-technetium oxide.
In a further embodiment, the device may further comprise a liquid chamber with an alkaline solution, more particularly with a sodium hydroxide solution, or a salt solution into which the 99mTc-technetium oxide can be routed for the formation of 99mTc-pertechnetate. In a further embodiment, the 100Mo-metal target is available in the form of a film, in the form of a powder, in the form of tubules, in the form of a grid structure, in the form of spheres or in the form of metal foam. In a further embodiment, the 100Mo-metal target is held by a thermally insulating mount. In a further embodiment, the device includes a circuit for conducting current through the 100Mo-metal target. In a further embodiment, the 100Mo-metal target is arranged in a heatable chamber, more particularly a ceramic chamber.



BRIEF DESCRIPTION OF THE DRAWINGS
Example embodiments will be explained in more detail below with reference to figures, in which:
FIG. 1 shows an example device for producing 99mTc-pertechnetate, according to one embodiment,
FIG. 2 shows another example device for producing 99mTc-pertechnetate, according to another embodiment,
FIG. 3 shows another example device for producing 99mTc-pertechnetate, according to another embodiment,
FIG. 4 shows a plan view of the 100Mo-metal film,
FIGS. 5-9 show the schematic representation of a 100Mo-metal target in different embodiments, and
FIG. 10 shows steps of an example method, according to one embodiment.



DETAILED DESCRIPTION
Some embodiments provide a method and a device by means of which a reaction product containing 99mTc can be obtained.
In some embodiments, a method for producing a reaction product containing 99mTc may comprise the following steps:

    
    
        providing a 100Mo-metal target to be irradiated,
        irradiating the 100Mo-metal target with a proton beam having an energy suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction, with a 100Mo(p, 2n)99mTc nuclear reaction being induced by the irradiation,
        heating the 100Mo-metal target to a temperature of over 300° C., more particularly of over 400° C.,
        obtaining the 99mTc made in the 100Mo-metal target in a sublimation-extraction process with the aid of oxygen gas, which is routed over the heated 100Mo-metal target forming 99mTc-technetium oxide in the process.
    
    


The 99mTc-technetium oxide can be discharged by the gas flow of the oxygen gas and thus be e.g. transported away from the 100Mo-metal target.
Certain embodiments are based on the discovery that 99mTc can be obtained directly in a 100Mo-metal target if the 100Mo-metal target is irradiated by a proton beam with a suitable energy, e.g. in a region between 20 MeV and 25 MeV. Thus, the 99mTc is obtained directly from a nuclear reaction occurring as a result of the interaction of the proton beam with the molybdenum atoms, according to the nuclear reaction 100Mo(p, 2n)99mTc.
The 99mTc produced in this manner is extracted with the aid of a sublimation process. To this end, the 100Mo-metal target with the 99mTc is heated to a temperature of over 300° C. If oxygen gas is now routed to the 100Mo-metal target, the 99mTc reacts with the oxygen, forming 99mTc-technetium oxide in the process, e.g. according to the equation 2Tc+3.5O2->Tc2O7. The molybdenum of the target likewise reacts with the oxygen, forming a molybdenum oxide in the process, e.g. by forming MoO3. However, since the molybdenum oxide is substantially less volatile than the technetium oxide, the technetium oxide is transported away by the oxygen gas routed over the 100Mo-metal target and can be discharged.
Here, the proton irradiation and the extraction of 99mTc by the oxygen gas with optional heating of the 100Mo-metal target can occur at the same time or alternately in succession.
Accelerating protons to the aforementioned energy usually requires only a single accelerator unit of average size, which can also be installed and used locally. Using the above-described method, 99mTc can be made locally in the vicinity or in the surroundings of the desired location of use, for example in the surroundings of a hospital. In contrast to conventional, non-local production methods which are accompanied by the use of large installations such as in nuclear reactors and the distribution problems connected therewith, a local production solves many problems. Nuclear medicine units can plan their workflows independently from one another and are not reliant on complex logistics and infrastructure.
The proton beam may be accelerated to an energy of between 20 MeV and 25 MeV. Restricting the maximum energy to no more than 35 MeV, more particularly to 30 MeV and most particularly to 25 MeV, avoids too high an energy of the particle beam triggering nuclear reactions which lead to undesired reaction products, e.g. other Tc isotopes than 99mTc, which should then be removed again in a complicated manner.
The 100Mo-metal target can be designed in such a way that the emerging particle beam has an energy of at least 5 MeV, more particularly at least 10 MeV. This makes it possible to keep the energy range of the proton beam in a region in which the occurring nuclear reactions remain controllable and in which undesired reaction products are minimized.
In one embodiment, the following step is additionally carried out:

    
    
        feeding the obtained 99mTc-technetium oxide, which was transported away, to an alkaline solution, more particularly to a sodium hydroxide solution, or to a salt solution, more particularly a sodium salt solution, to form 99mTc-pertechnetate.
    
    


This may provide an advantageous reaction product containing 99mTc because 99mTc-pertechnetate can easily be distributed and processed and can be a starting point for the production of radiopharmaceuticals, e.g. SPECT tracers.
In the case of a sodium hydroxide solution, the reaction equation is: Tc2O7+2NaOH->2NaTcO4+H2O.
Excess O2, which originates from the oxygen gas and was routed through the liquid, can be cleaned and returned to the gas supply, e.g. within a closed loop.
In one embodiment, the 100Mo-metal target is available in the form of a film, more particularly as a stack of films of a plurality of films arranged one behind the other in the beam direction. This makes it possible to obtain 99mTc in a particularly effective fashion and, moreover, it is easier to heat the 100Mo-metal target to the temperature required for sublimation. Alternative forms are possible, for example, the 100Mo-metal target can be available in the form of a powder, in the form of tubules, in the form of a grid structure, in the form of spheres or in the form of metal foam.
To this end, the 100Mo-metal target can be held by a thermally insulating mount, e.g. epoxy resin strengthened by G20.
Heating to the desired temperature can already be achieved by proton beam irradiation because the proton beam on its part transfers thermal energy onto the 100Mo-metal target. Optionally, the temperature of the 100Mo-metal target can be set by matching the energy and/or intensity of the proton beam and/or the strength of the gas flow, which can e.g. be controlled by a valve, to one another or by controlling one or more of these variables. Heat supply by the proton beam and heat dissipation by the mount and by convection cooling can thus be matched to one another. This enables the equilibrium temperature to be set in the 100Mo-metal target.
In particular, the 100Mo-metal target can be heated by proton beam irradiation only. Additional heating devices are not mandatory.
In an alternative and/or additional embodiment, the 100Mo-metal target can be heated with the aid of a current which is conducted through the 100Mo-metal target, i.e. it can be heated with the aid of a circuit, e.g. by the Ohmic heating occurring in this case. The temperature to be achieved can be set in a simple manner by controlling the electric circuit.
In an alternative and/or additional embodiment, the 100Mo-metal target can be arranged in a chamber, e.g. in a ceramic chamber, which is heated specifically for heating the 100Mo-metal target. This can also be used to reach or set the temperature required for the sublimation.
In some embodiments a device for producing a reaction product containing 99mTc may comprise:

    
    
        a 100Mo-metal target,
        an accelerator unit for providing a proton beam which can be directed at the 100Mo-metal target, the proton beam having an energy which is suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction when the 100Mo-metal target (15) is irradiated by the proton beam (13),
        a gas supply line for routing oxygen gas onto the irradiated 100Mo-metal target for forming 99mTc-technetium oxide,
        a gas discharge line for discharging the sublimated 99mTc-technetium oxide.
    
    


In one embodiment, the device can furthermore comprise:

    
    
        a liquid chamber with an alkaline solution, more particularly with a sodium hydroxide solution, or a salt solution into which the 99mTc-technetium oxide can be routed for the formation of 99mTc-pertechnetate.
    
    


The device can furthermore comprise a heating device for heating the 100Mo-metal target to a temperature of over 400° C.
FIG. 1 shows one embodiment of a device for producing 99mTc-pertechnetate.
An accelerator unit 11, e.g. a cyclotron, accelerates protons to an energy of approximately 20 MeV to 25 MeV. The protons are then, in the form of a proton beam 13, directed at a 100Mo-metal target 15, which is irradiated by the proton beam. The 100Mo-metal target 15 is designed such that the emerging particle beam has an energy of approximately at least 10 MeV.
Illustrated here is a 100Mo-metal target 15 in the form of a plurality of metal films 17, arranged one behind the other in the beam direction and arranged perpendicular to the beam propagation direction. As illustrated in FIG. 4, the area of the film 17 is greater than the cross-sectional profile of the proton beam 13.
The metal films 17 are held by a thermally insulating mount 19 which, for example, can be manufactured in large parts from epoxy resin strengthened by G20.
The proton beam 13 interacts with the 100Mo-metal target 15 as per the 100Mo(p, 2n)99mTc nuclear reaction, from which 99mTc then emerges directly.
Here, the proton beam 13 is controlled in terms of its intensity such that so much thermal energy is transferred to the metal films 17 during the irradiation that the metal films 17 moreover heat up to a temperature of over 400° C.
Oxygen gas is routed over the 99mTc from an oxygen source via a valve 21 which controls the gas flow.
At such temperatures, the 99mTc made in the metal films 17 reacts with the oxygen and makes 99mTc-technetium oxide, e.g. according to the equation 2Tc+3.5O2->Tc2O7. The 100Mo likewise reacts with the oxygen forming a molybdenum oxide in the process, e.g. forming 100MoO3. Since the MoO3 is significantly less volatile than the technetium oxide, the technetium oxide is transported away by the oxygen gas routed over the 100Mo-metal target 15 and can be discharged.
The gas flow, the energy transmitted by the proton beam 13 and the heat loss through the mount 19 of the 100Mo-metal target 15 are matched to one another such that the temperature required for the sublimation-extraction process is reached and maintained.
The gas containing technetium oxide is subsequently routed into a liquid column 23 containing a salt solution or alkaline solution and effervesced there such that 99mTc-pertechnetate is formed by a reaction of the technetium oxide with the solution, e.g. sodium pertechnetate in the case of a sodium hydroxide solution or a sodium salt solution. In the case of a sodium hydroxide solution, the reaction equation can, for example, be: Tc2O7+2 NaOH->2NaTcO4+H2O.
Subsequently, the 99mTc-pertechnetate now made can be used as starting point for the production of radiopharmaceuticals, e.g. of SPECT tracers.
The O2 rising in the liquid column 23 can be routed back to the supplying gas inlet in an e.g. closed loop 25.
FIG. 2 shows another embodiment that substantially corresponds to the embodiment shown in FIG. 1.
This embodiment has a device 27, by means of which electric current can be conducted through the metal films 17, i.e. the metal films 17 are part of a circuit. The current which flows through the metal films 17 heats the metal films 17 by resistance heating. The temperature to which the metal films 17 are heated can thus be controlled in a simple manner, and so the metal films 17 reach a temperature required for the sublimation-extraction process.
FIG. 3 shows a further embodiment, in which, compared to the embodiment shown in FIG. 1, a heating device 29 is arranged in the irradiation chamber, the latter being able to be made of e.g. ceramics, by means of which heating device the temperature required for the sublimation-extraction process is produced.
Embodiments shown in FIG. 1 to FIG. 3 for heating the metal films 17 can also be combined with one another.
In FIGS. 1-3, the 100Mo-metal target is embodied as metal film. Other embodiments are possible, e.g., as shown in FIGS. 5-9.
In FIG. 5, the 100Mo-metal target is embodied as a multiplicity of tubules.
In FIG. 6, the 100Mo-metal target is available in powder form.
In FIG. 7, the 100Mo-metal target is shown as a multiplicity of spheres.
In FIG. 8, the 100Mo-metal target is shown in the form of a metal foam block.
In FIG. 9, the 100Mo-metal target is shown in the form of a grid.
What is common to all these embodiments is that the 100Mo-metal target 15 has a large surface area, which can react with the supplied oxygen gas. This leads to an efficient extraction of the 99mTc-technetium oxide.
FIG. 10 shows a schematic diagram of example steps of a method according to one embodiment.
Initially, a 100Mo-metal target is provided (step 41).
The target is subsequently irradiated by a proton beam which was accelerated to an energy of 10 MeV to approximately 25 MeV (step 43).
After irradiation of the target, the target is heated to a temperature of over 400° C. (step 45) in order, with the aid of a sublimation-extraction process, to extract the 99mTc made in the target.
To this end, oxygen gas is routed over the target (step 47), the forming 99mTc-technetium oxide being sublimated and discharged (step 49).
99mTc-pertechnetate can be obtained from the 99mTc-technetium oxide with the aid of a sodium hydroxide solution or a sodium salt solution (step 51).
LIST OF REFERENCE SIGNS


    11 Accelerator unit
    13 Proton beam
    15 100Mo-metal target
    17 Metal film
    19 Mount
    21 Valve
    23 Liquid column
    25 Loop
    27 Circuit
    29 Heating device
    Step 41
    Step 43
    Step 45
    Step 47
    Step 49
    Step 51

## Claims

1. A method for producing a reaction product containing 99mTc, comprising:
providing a100Mo-metal target to be irradiated,
accelerating protons with only a single acceleration unit to form a proton beam having an energy suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction,
irradiating the 100Mo-metal target with the proton beam having the energy suitable for inducing the 100Mo(p, 2n)99mTc nuclear reaction,
heating the 100Mo-metal target to a temperature of over 300° C., and
obtaining the 99mTc made in the 100Mo-metal target in a sublimation-extraction process with the aid of oxygen gas, which is routed over the 100Mo-metal target forming 99mTc-technetium oxide in the process.

2. The method of claim 1, additionally comprising feeding the obtained 99mTc-technetium oxide to an alkaline solution to form 99mTc-pertechnetate.

3. The method of claim 1, wherein the 100Mo-metal target is in the form of a film, in the form of a powder, in the form of tubules, in the form of a grid structure, in the form of spheres, or in the form of metal foam.

4. The method of claim 1, wherein the 100Mo-metal target is held by a thermally insulating mount.

5. The method of claim 1, wherein heating of the 100Mo-metal target is achieved by the irradiation by the proton beam.

6. The method of claim 1, wherein the heating is achieved by conducting current through the 100Mo-metal target.

7. The method of claim 1, wherein the heating is achieved by heating a chamber in which the 100Mo-metal target is arranged.

8. A device for producing a reaction product containing 99mTc, comprising:
a 100Mo-metal target,
a single accelerator unit for accelerating protons, with only the single acceleration unit, to form a proton beam directed at the 100Mo-metal target to thereby irradiate the 100Mo-metal target, the proton beam having an energy which is suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction when the 100Mo-metal target is irradiated by the proton beam,
wherein the device is configured to heat the 100Mo-metal target to a temperature of over 300° C., and
a sublimation-extraction system for extracting 99mTc, including:
a gas supply line for routing oxygen gas onto the irradiated and heated 100Mo-metal target forming 99mTc-technetium oxide by sublimation, and
a gas discharge line for extracting the sublimated 99mTc-technetium oxide.

9. The device of claim 8, further comprising a liquid chamber with an alkaline solution into which the 99mTc-technetium oxide is routed for the formation of 99mTc-pertechnetate.

10. The device of claim 8, wherein the 100Mo-metal target is available in the form of a film, in the form of a powder, in the form of tubules, in the form of a grid structure, in the form of spheres or in the form of metal foam.

11. The device of claim 8, wherein the 100Mo-metal target is held by a thermally insulating mount.

12. The device of claim 8, comprising a circuit for conducting current through the 100Mo-metal target to heat the 100Mo-metal target to the temperature of over 300° C.

13. The device of claim 8, wherein the 100Mo-metal target is arranged in a heatable chamber to heat the 100Mo-metal target to the temperature of over 300° C.

14. The method of claim 1, additionally comprising feeding the obtained 99mTc-technetium oxide to a sodium hydroxide solution.

15. The device of claim 8, further comprising a liquid chamber with a sodium hydroxide solution into which the 99mTc-technetium oxide is routed for the formation of 99mTc-pertechnetate.

16. The method of claim 1, additionally comprising feeding the obtained 99mTc-technetium oxide to a salt solution to form 99mTc-pertechnetate.

17. The device of claim 8, further comprising a liquid chamber with a salt solution into which the 99mTc-technetium oxide is routed for the formation of 99mTc-pertechnetate.

18. A method for producing a reaction product containing 99mTc, comprising:
providing a 100Mo-metal target to be irradiated,
accelerating protons in an acceleration unit to form a proton beam,
irradiating the 100Mo-metal target with the proton beam having an energy suitable for inducing a 100Mo(p, 2n)99mTc nuclear reaction,
heating the 100Mo-metal target, by the irradiation by the proton beam, to a temperature of over 300° C., and
obtaining the 99mTc made in the 100Mo-metal target in a sublimation-extraction process with the aid of oxygen gas, which is routed over the 100Mo-metal target, heated to the temperature over 300° C., forming 99mTc-technetium oxide in the process.

19. The method of claim 18, comprising forming the proton beam with a single acceleration unit.

20. The method of claim 18, further comprising feeding the formed 99mTc-technetium oxide to an alkaline solution to form 99mTc-pertechnetate.

21. The method of claim 18, further comprising feeding the formed 99mTc-technetium oxide to a salt solution to form 99mTc-pertechnetate.

22. The method of claim 18, wherein the 100Mo-metal target comprises a film in the form of: a powder, tubules, a grid structure, spheres, or a metal foam.

23. The method of claim 18, comprising holding the 100Mo-metal target with a thermally insulating mount.

24. The device of claim 8, wherein the 100Mo-metal target is heated to the temperature over 300° C. by the irradiation of the proton beam from the single accelerator unit.