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.
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.
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.
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.
Example embodiments will be explained in more detail below with reference to figures, in which:
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:
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:
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:
In one embodiment, the device can furthermore comprise:
The device can furthermore comprise a heating device for heating the 100Mo-metal target to a temperature of over 400° C.
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
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.
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.
Embodiments shown in
In
In
In
In
In
In
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.
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).
Number | Date | Country | Kind |
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10 2010 006 434 | Feb 2010 | DE | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/EP2011/051017 | 1/26/2011 | WO | 00 | 8/1/2012 |
Publishing Document | Publishing Date | Country | Kind |
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WO2011/092174 | 8/4/2011 | WO | A |
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