JP5263853B2 - Radionuclide production method and apparatus using accelerator - Google Patents

Description

  The present invention relates to a method and apparatus for simultaneously producing multiple nuclides using an accelerator, and in particular, can efficiently produce radionuclides such as molybdenum 99 and technetium 99m, which are in great demand as radiopharmaceuticals regardless of the heat generated during irradiation. The present invention relates to a method and an apparatus for producing a radionuclide using an accelerator.

1. Molybdenum 99 and Technetium 99m
Technetium 99m (Tc-99m, half-life 6 hours), which is used worldwide in nuclear medicine and diagnostic imaging, is the leading role of over 70% of the radioisotopes used in nuclear medicine. Nuclide obtained as a daughter nuclide of molybdenum 99 (Mo-99, half-life 66 hours). The nuclide required as a radiopharmaceutical is Tc-99m, and Mo-99 is only its raw material.

  As a specific method for producing Tc-99m, a technique of simply eluting and recovering Tc-99m produced by the attenuation of Mo-99 with a physiological saline solution or the like is mainly used. Therefore, the production amount (radioactivity) of Mo-99 dominates the production amount (radioactivity) of Tc-99m. Since this feature can be thought of as squeezing milk (Tc-99m) from dairy cows (Mo-99), this mechanism is called "Milking" or "Generator" and is commercialized. It is commercially available.

2. Main production method and characteristics of Mo-99 Mo-99 currently distributed in the market is recovered as a product in the reactor. Specifically, a fission product of uranium 235 (U-235; isotopic enrichment of 90% or more) concentrated to a high concentration is applicable ( ²³⁵ U (n, f) ⁹⁹ Mo). The reactors that produce Mo-99 by this reaction are few and unevenly distributed for the purpose of global market supply (Canada, Netherlands, Belgium, France, South Africa, etc.). Anxiety remains.

  In addition, reactor-specific problems include: 1) potential operational risks including reactor aging, 2) conflict with nuclear non-proliferation resistance caused by the use of high-concentration uranium (U-235 less than 20%) However, Mo-99 cannot be obtained sufficiently from low concentration U). 3) Radiotoxicity of ultra-long half-life nuclear waste and treatment / handling of waste. Therefore, although the benefit side in the medical use of Mo-99 / Tc-99m is enormous, the magnitude of the problems accompanying it cannot be ignored. Despite stable and large demands on the market, it is not easy to install a nuclear reactor because of the great investment and maintenance costs. In addition, since nuclear weapons can be developed, it is also true that there are restrictions on installation depending on the country, and the stable supply of Mo-99 is an international issue. In Japan only, there are many nuclear reactors, but Mo-99 is not produced and is 100% dependent on foreign countries. The importance of preparing a domestic Mo-99 supply system has been accused. However, there is no concrete progress for the reasons mentioned above.

3. On the other hand, due to the usefulness of Tc-99m, research on a method for producing Mo-99 using another nuclear reaction has been widely promoted. Specifically, the activation method of Mo-98 or Mo-100 by heat or fast neutrons is first mentioned ( ⁹⁸ Mo (n, γ) ⁹⁹ Mo or ¹⁰⁰ Mo (n, 2n) ⁹⁹ Mo). Since this reaction uses neutrons derived from a nuclear reactor or accelerator, it is not necessary to use highly enriched uranium. Therefore, especially the regulatory issues are cleared. In addition, not only is it possible to reduce the cost of capital investment and maintenance costs related to expensive reactors to about 1/10 or less, but it is not necessary to consider the waste problem. However, it is not easy to control the production, that is, the criticality / shutdown of the reactor, whereas the accelerator can be turned on / off very easily.

  However, the production method shown here, specifically, the activation method using neutrons has a drawback that the yield is only about 1/10 compared to the case of directly obtaining Mo-99 derived from fission. is there. Moreover, as a result of Mo-99 being produced in Mo-98 or Mo-100, isotope dilution occurs (= specific activity is low), and these cannot be separated by actual operation techniques. Therefore, the formulation method performed after that also has the subject that the establishment method used as the present standard cannot be applied. However, other methods for avoiding problems have been developed, and it is not impossible to obtain a Tc-99m preparation.

  As an alternative to the production method using an accelerator, a method of irradiating a target with charged particles, more specifically protons (protons), has been studied, but at a practical level (for example, a large amount of radioactivity that can be used for medical purposes). Have not yet been reported).

  In addition, examples of a subcritical reactor and a hybrid manufacturing method using an accelerator as a neutron source sufficient to cause criticality have been reported. In this case, the molybdenum irradiation method is in accordance with other nuclear reactor methods.

  Prior arts for the whole method using accelerators have not yielded a practical level of yield (radioactivity) in any case, and have been evaluated through examination or verification of the concept.

  That is, Non-Patent Document 1 estimates the amount of Tc-99m and Mo-99 produced when Mo-100 is irradiated with protons with an energy range of 68 → 8 MeV and Non-Patent Document 2 with 22 → 10 MeV. It is. Although it is written that any nuclide will be obtained in a yield according to energy, there is no description about a specific irradiation method or apparatus configuration. It is a previous paper on the experimental element that explores so-called feasibility, and can be said to be a report investigating physical phenomena.

Non-Patent Documents 3 and 4 describe that radionuclides are simultaneously manufactured by arranging different types of targets in series and simultaneously irradiating them, although the nuclides to be manufactured are different. In Non-Patent Document 3, the target substances are a gas target for ¹¹ C production and a liquid target for ¹⁸ F production, and in Non-Patent Document 4, a ¹⁶ O (p, pn) ¹⁵ O reaction as a previous stage target. Oxygen gas for use with ¹⁶ O (p, α) ¹³ N reaction water as a post target and labeled with ¹⁵ O, such as [ ¹⁵ O] CO ₂ , [ ¹⁵ O] H ₂ O And ¹³ N-labeled compounds such as ¹³ NH ₃ , ¹³ N ₂ O and ¹³ N ₂ are obtained.

  On the other hand, in Non-Patent Document 5, in order to make two types of long nuclides at the same time, Na-22 and Ge-68 (→ Ga-68) are made by using two Mg and Ga targets, or Rb and Ga. In the same manner to produce Sr-82 (→ Rb-82) and Ge-68 (→ Ga-68). Here, → indicates a daughter nuclide of the generator.

Lagunas-solar, M.C. et al. (1991) Cyclotron production of NCA 99mTc and 99Mo. An alternative non-reactor supply source of instant 99mTc and 99Mo → 99mTc generators. Appl. Radiat. Beaver, J.E. and Hupf, H.B. (1971) Production of 99mTc on a medical cyclotron: A feasibility study.J. Nucl. Med. 12 (11), 739-741 Kim, S.W., et al. (2007) A study on a tandem target for a simultaneous production of C-11 and F-18. J. Label. Compd. Radiopharm. 50, 567-568 Koh, K. et al. (1983) External tandem target system for efficient production of short-lived positron emitting radionuclides. IEEE Trans. Nucl. Sci. NS-30, 3064-3066 G. F. Steyn, et al. (2008) Development of Tandem Targets for a Vertical Beam Target Station.12th Workshop on Targetry and Target Chemistry, Seattle

  By irradiating protons to a Mo-100 target enriched with only Mo-100 equivalent to about 10% among the seven types of molybdenum isotopes that exist in nature, Mo- with high radionuclide purity according to the incident energy It has long been confirmed that 99 and / or Tc-99m are produced. However, even now, production using charged particles is not performed. The reason for this is that the half-lives of Mo-99 and Tc-99m are not suitable for efficient production, and the isotope enriched Mo-100 is expensive, resulting in poor cost competitiveness in the market. However, technically, the problem of heat generation during irradiation is large.

  On the other hand, in the technique described in Non-Patent Document 5, when producing the target nuclide, it is necessary to prepare a target substance in some container, in this case, in the capsule in order to compensate for melting. However, the work (preparation) for sealing the target is very troublesome. Further, the material constituting the capsule itself absorbs the beam energy and attenuates the energy necessary for the original nuclear reaction (particularly for the second stage). At the same time, miscellaneous nuclides derived from the capsule material are generated, which may adversely affect the quality. Furthermore, since the two targets are aligned and fixed, it seems necessary to take them out at the same time.

  The present invention has been made to solve the above-mentioned conventional problems, and enables efficient production of radionuclides such as molybdenum 99 and technetium 99m, which are in great demand as radiopharmaceuticals, regardless of the heat generated during irradiation. Let it be an issue.

The heat generation during irradiation is represented by the product of the beam energy and the current value, and is estimated to be, for example, 40 [MeV] × 10 [μA] = 400 [W]. When Mo-99 and Tc-99m required for practical use are to be obtained by a reaction represented by the nuclear reaction formulas ¹⁰⁰ Mo (p, pn) ⁹⁹ Mo and ¹⁰⁰ Mo (p, 2n) ^99m Tc) The required current value is 1 to 2 [mA], that is, the heat generation estimate is 40 to 80 [kW]. If recoil neutrons generated by the nuclear reaction are also used, it contributes to the production of Mo-99 and Tc-99m. In that case, the resulting heat generation does not significantly affect the heat generation estimation. The establishment of the irradiation system is determined by how the heat quantity is removed and dispersed on the target side that receives the beam. A practical heat resistance density in a system having a general cooling efficiency is considered to be several hundreds [W / cm ² ] at most. For example, when 300 [W / cm ² ] is set, a necessary target area is required. Ranges from 100 to 200 [cm ² ]. However, the spread of the area means an increase in the amount of target preparation, which further reduces the low specific activity, and there is a concern about the adverse effect on the subsequent processing. Furthermore, in order to diffuse the irradiated beam so as to be evenly distributed over all the prepared wide target areas of 100 to 200 [cm ² ], another technical problem increases.

  On the other hand, if the target is a replacement type (for example, a turbine rotary type in which the target 70 is disposed on the six rotor blades shown in FIG. 1), the beam 10 is irradiated over a substantially wide range without increasing the diameter. Can be possible. In FIG. 1, 16 is a beam duct, 72 is a rotating shaft, and 74 is a rotating body. Here, the rotating body 74 can be reduced in weight as being hollow.

  Further, as illustrated in FIG. 2, since there is only a half-circle target at the maximum on the beam trajectory, the heat generation amount per target when viewed in unit time can be halved. This does not change regardless of the number of unit rotations of the rotating body.

  For example, it is assumed that each target has a thickness capable of absorbing energy of 5 MeV and a beam current of 100 μA is applied.

  The rotating body rotates once per second in FIG. 2 (A) and twice per second in FIG. 2 (B). Regardless of the number of rotations, since the maximum chance (location) where the beam can collide is up to 0 ≦ θ ≦ π from the viewpoint of one target, the time for heat generation is also reduced to less than half.

  Therefore, Δ5 (MeV) × 100 (μA) = 500 (W) = 500 (J / S) and the calorific value per target given by a simple calculation is 0.5 sec. Can be reduced to half (250).

  Considering the entire rotating body, there are always several targets on a given beam axis, so there is no change in the amount of heat generated per unit time, for example, per second, and constant radioactivity can be generated. .

  The configuration for rotating the target is not limited to that shown in FIG. 1. For example, as shown in FIG. 3, six blades of rotating bodies 74A and 74B are arranged opposite to each other, or as shown in FIG. 74 and 12 blades 75 can be arranged in tandem.

  As the target holding structure, as shown in FIG. 5, for example, a target 70 made of a single metal molybdenum thin film having a thickness of 5 mm or less is fixed to a U-shaped holder 78, or as shown in FIG. For example, molybdenum trioxide or a powder-sintered target 70 can be sandwiched and held between thin films 80 made of aluminum or gold that do not get in the way when activated.

  Moreover, heat removal is required for any irradiation method of the target. However, if a cooling medium is present on the beam trajectory, it has a beam energy absorption capability proportional to the product of thickness and density, whether it is water or gas. That is, energy prepared for causing the intended nuclear reaction is lost to the cooling medium, and the target reaction may not be sufficiently performed. For this reason, a low density, for example, helium or air is usually used to cool the target on the beam trajectory. Arbitrary positions and number of devices (for example, jet ports) 50 for jetting them can be installed inside the irradiation device, and as shown in FIG. 7, the target 70 can be cooled and used for the driving force of the rotating body 74. It is possible to squirt on a specially prepared wing instead of the target. In the vicinity of an irradiation device where an intense radiation environment is expected, it is significant that a rotational force can be obtained with a simple mechanism as compared with a motor drive that requires electrical control.

  For example, even in the case of water, since the density differs greatly between liquid and gas (water vapor), there is often no great problem even if water vapor exists on the beam trajectory. Therefore, a small amount of water can be ejected, and the vaporization heat of water during evaporation can be expected to have a great effect on cooling. As shown in FIG. 8, the gravity and the centrifugal force of the rotating body can be applied to the ejection of the small amount of liquid. Although the rotational drive source used here is not particularly defined, a small diameter hole 74X can be arbitrarily formed in the lower part of the cooling water storage area 74W provided at the center of the rotating body to secure a water channel. A rotary blade serving as a target is provided at the outlet of the water channel, and water is supplied from the center of the rotary body toward this. Since the target itself generates heat under the influence of irradiation, all of the small amount of water boils here, and at the same time as the vaporization, the heat of the target can be taken as the heat of vaporization. Optimal control, such as the amount of water, can be determined comprehensively, including the hole diameter, channel shape, and rotational speed. Since the final use of cooling water is "heat removal by vaporization", some water leakage does not affect the function (where the water leakage is from and where it is intended to discharge is not essential, it is vaporized from multiple locations Is more efficient). Furthermore, there is an advantage that the manufacture and assembly of the parts constituting this function are remarkably facilitated.

  In addition to the vaporized moisture, the heat transferred to the released helium or the like needs to be released out of the system. Moreover, in order to implement | achieve the above structure, collection | recovery and reuse as a substance (all cooling media) are needed. Therefore, the irradiation device needs to be a sealed space except for piping provided for cooling the entire system.

  Inside the space, a rotating body can be provided on the left and right sides of the beam trajectory or arbitrarily. A condenser is provided at the top of the rotating body to liquefy and recover the vaporized vapor. Probably not all liquid can be recovered, so it is possible to fill the interior space with cooling water in advance. In this case, a part of the cooling water is sucked with a pump or the like and returned to the center of the rotating body, thereby completing a series of cooling water supply systems. The space can have a simple opening / closing structure so that the target can be easily taken out after irradiation.

  In addition, Mo-99 and Tc-99m, which are examples of the target production nuclide of the present invention, have a half-life difference of about 10 times. By optimizing the irradiation operation method using this difference, it becomes possible to increase the total amount of radioactivity generated in a certain irradiation period of Tc-99m to be finally used.

The radioactivity of a nuclide produced by irradiation is determined by its half-life T,
S = 1−e− ^λt (1)
λ = 0.693 / T (2)
It can be expressed as Here, S is a saturation rate, λ is a decay constant (s ⁻¹ ), and t is an irradiation time (s).

  Saturation rate represents the generation and decay of radioactivity with respect to the length of irradiation time in the production of radionuclides by an accelerator. When S = 1 (100%), the generation and decay are balanced. (Approaching 1 after prolonged irradiation). Therefore, irradiation after a certain time hardly contributes to the production of radioactivity. Generally, it is appropriate that the irradiation time is about half-life (S = 0.5), and 2.5 half-life irradiation (S = 0. 82) is a widely used technique. Therefore, for mass production, there is no appropriate method other than increasing the beam current value.

  In order to produce Mo-99 (T = 66 [hr]) by irradiating Mo-100 with protons, irradiation for about 3 to 5 days is efficient for the above reasons, but Tc-99m ( The irradiation period required for T = 6 [hr]) is much shorter as shown in FIGS. Actually, since the nuclide to be used is Tc-99m, the irradiation of the energy region suitable for the generation of Tc-99m is performed at the same time by using the irradiation of the energy region capable of efficiently generating Mo-99. If it becomes possible to efficiently extract the Tc-99m with the necessary irradiation period period, the total amount of Tc-99m becomes a considerable amount. For example, considering that Tc-99m is supplied to a place where it is needed, it is possible and convenient for Tc-99m to supply the source at a distance that does not require time to transport the source. When supplying to a place where time is required, the physical attenuation of Mo-99 is suppressed more than that of Tc-99m, so that the supply with Mo-99 is efficient. Furthermore, with Mo-99, there is also an advantage that Tc-99m, which is about 1.7 times the original Mo-99 radioactivity, can be obtained in one week. Therefore, the motivation for studying this irradiation technique is to answer the need for the production demand of Mo-99 together with Tc-99m.

  Fig. 10 (Scholten, B et al., Excitation functions for the cyclotron production of 99mTc and 99Mo., Appl. Radiat. Isot. 51 (1999) 69-80) shows the relationship between the cross-sectional area (ease of production) and irradiation energy. Show. In the figure, attention was paid to the fact that the effective irradiation energy range of Tc-99m having a short half-life is shifted to the lower side so as to partially overlap the efficient irradiation energy range of Mo-99 having a long half-life. That is, the incident energy of a proton capable of efficiently producing molybdenum 99 from Mo-100 is 60-20 MeV, while the incident energy of a proton capable of efficiently producing technetium 99m is 30-20 MeV.

  Therefore, considering the ease of making the target, the effective energy region for manufacturing Mo-99 is 40 → 20 [MeV] and that of Tc-99m is 20 → 10 [MeV], as shown in FIG. As described above, the first target 11 for producing Mo-99 is placed on the high energy side, and the beam for Tc-99m is collided with the beam 10 having the residual energy attenuated in accordance with the passage of the first target 11 on the downstream side. By installing the two targets 12, the present invention can be realized. The beam operation is important in that the second stage target 12 is exchanged with a 6-hour irradiation cycle that is a half-life of Tc-99m.

  The attenuation of the beam energy varies depending on the situation depending on the total of the incident energy and the thickness and density of the passing substance (target). The thicker and the higher the density, the easier it is to stop the beam. The higher the incident energy, the harder the beam to stop (the energy is less likely to drop). FIG. 11 shows an example in which the incident energy is 40 MeV and the thickness of each target is 0.25 mm (250 μm). The number after the arrow is the energy that is attenuated and the number in parentheses is the target. It is lost energy.

  The number of target stages is not limited to two, but may be three, 11, 12, 13 as shown in FIG. 11 (B), or four, 11, 12, 13, 14 as shown in FIG. 11 (C). It is also possible to increase the number of stages.

Further, all the targets shown in FIG. 11 may be the same Mo-100 regardless of the generated nuclides, which contributes to the simplification of the preparation work. Further, if a substance containing a Mo-100, chemical type is not may be arbitrary, for example, elemental metals Mo-100 or the like MoO ₃ which is a metal oxide can be utilized. In order to simplify the preparation work, all chemical compositions may be the same. Of course, when the best chemical form is desired for a subsequent chemical reaction, the chemical composition may be different among a plurality of targets.

  This invention is made | formed based on the said knowledge, The said subject is solved by the manufacturing method of the radionuclide by the accelerator characterized by replacing a several solid target during beam irradiation.

  Here, the target is supported by a rotating body and rotated around an axis outside the beam trajectory, so that one target supported by the rotating body receives a beam in a heated state and does not receive a beam. The cooling state can be taken.

  In addition, the rotating body can be intermittently rotated to stop the target one after another at the irradiation position.

  Alternatively, the rotating body can be reciprocally rotated.

  The target can be supported as a rotor blade on the outer periphery of the turbine-like rotor.

  The target can be tilted with respect to the beam axis.

  In addition, a plurality of the rotating bodies may be provided across the beam so that the targets supported by the rotating bodies alternately hit the beam.

  The rotating body can be rotated by a fluid used for cooling the target.

  Further, a part of the fluid used for cooling the target can be guided to the inside of the rotating body and supplied to the target site via a flow path extending in the centrifugal force acting direction of the rotating body.

  Further, the target can be supported on the rotation plane of the turret-shaped rotating body.

  Further, the periphery of the rotating body and the target can be filled with a cooling medium.

In addition, a plurality of solid targets arranged in series are irradiated with a particle beam from an accelerator,
Each beam reacts with energy attenuated as the beam passes through the target,
Further, by exchanging the target according to the irradiation time of the target, a plurality of nuclides having different half-lives can be obtained efficiently.

  In addition, the target for obtaining a nuclide with a short half-life is obtained by continuing or suspending the irradiation of the beam until the target for obtaining the nuclide having a long half-life is collected after the irradiation of the total irradiation amount is completed. Can be recovered by exchanging them sequentially.

  Further, the irradiation time until the exchange can be set to a period of about 0.5 to 2.5 times the half-life of the production nuclide.

  Further, at least one material of the target may be a metal and / or a metal oxide.

  In addition, a plurality of nuclides having different half-lives can be obtained separately from the target having the same chemical composition and / or isotope abundance ratio.

  The particles may be protons and the target may be molybdenum 100.

  Moreover, the nuclide produced can be molybdenum 99 and technetium 99m.

  Further, the incident energy of protons used for manufacturing the molybdenum 99 can be 60-20 MeV, or the incident energy of protons used for manufacturing the technetium 99m can be 30-20 MeV.

  In addition, the target molybdenum 100 is activated by recoil neutrons generated when protons collide, and as a result, molybdenum 99 and / or technetium 99m can be manufactured.

  The present invention also provides a radionuclide production apparatus using an accelerator comprising means for replacing a plurality of solid targets during beam irradiation.

  According to the present invention, it is possible to efficiently produce radionuclides such as molybdenum 99 and technetium 99m, which are in great demand as radiopharmaceuticals regardless of heat generation during irradiation.

  For example, Tc-99m of a total amount of 171 [Ci] can be obtained by irradiation of only 170 [μA] × 2.5 [day]. This is a method that has been considered in order to obtain the same yield. Specifically, the required beam current of 1 [mA] class can be reduced to 1/5 or less, and the irradiation time can be reduced to about half. become. Therefore, the time and energy saving effect of the present invention is extremely large.

  At the same time, by establishing a method for producing Tc-99m / Mo-99 by charged particle irradiation, it is possible to review the production system dependent on Mo-99, that is, a reactor, which is required worldwide. This not only greatly reduces capital expenditures and operating and maintenance costs, but also allows the nuclear-related political and waste issues to be completely ignored. Furthermore, it is not impossible to establish a manufacturing facility with the same level of Mo-99 production capacity at the private level if the cost is commensurate with recovering and reusing the concentrated isotope Mo-100 used for the target.

The figure which shows the basic composition of the rotary target which concerns on this invention Diagram showing the action of the rotary target Diagram showing a variation of the rotary target The figure which shows another modification similarly An exploded perspective view showing an example of a target holding structure in a rotary target An exploded perspective view showing another example The perspective view which shows another modification similarly An exploded perspective view showing still another example The time chart which shows the effect | action of embodiment of this invention Diagram showing the relationship between cross-sectional area and irradiation energy The side view which shows the basic composition of embodiment of this invention The perspective view which shows the principal part structure of 1st Embodiment of this invention. Similarly, an exploded perspective view showing a detailed configuration of the second embodiment Sectional view of the first target part The perspective view which shows the principal part structure of 3rd Embodiment of this invention. The perspective view which similarly shows the principal part structure of 4th Embodiment. The perspective view which shows the modification of a rotary target Sectional drawing which shows the principle of the modification shown in FIG. The perspective view which shows the 1st target part of 5th Embodiment of this invention which employ | adopted the modification shown in FIG. Side view showing another modification of the rotary target The perspective view which shows the principal part structure of 6th Embodiment of this invention. Side view showing the operation of the sixth embodiment (A) perspective view and (B) cross-sectional view for explaining a method of replacing a rotating body The perspective view which similarly shows the approach state of a robot hand Similarly (A) When opened and (B) Holding vertical section Time chart of Example 1 Time chart of Example 2 Time chart of Example 3 The figure which shows the structural example for implementing Example 3. FIG. Time chart of Example 4

  Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

  In the first embodiment of the present invention, as shown in FIG. 12, for example, six upper targets 11 disposed on the circumference of a rotating body 74 disposed on the upstream side of the beam 10 irradiated from the accelerator 8. And a rear target unit 40 including a disc-shaped rear target 12 and a support 45 for holding the rear target 12, which are disposed on the downstream side of the upper target unit 20. .

  Both the front stage target 11 and the rear stage target 12 are made of Mo-100, and the front stage target 11 mainly generates Mo-99, and the rear stage target 12 generates Tc-99m.

  Mo-99 and Tc-99m can be efficiently manufactured by exchanging the post-stage target 12 about every 6 hours that is the half-life of the post-stage target 12 until the half-life of the pre-stage target 11 is reached. At this time, the beam current value may be determined according to the required amounts of Tc-99m and Mo-99, and it is considered that the required amount is about 100 to 200 [μA].

  When the required amount of Tc-99m is 170 Ci / week (Mo-99 production amount is 100 Ci / week), the irradiation current is 15 μA in the normal range, 170 μA in the challenging region, and 1 mA required in the fast neutron method. Table 1 shows the results of comparison between these three types.

  Irradiation time is a realistic 6 hours (Tc-99m half-life), 12 hours, which is about half a day, 66 hours, which is the half-life of Mo-99, and 4 types of 7 days required by the fast neutron method. did.

  The Mo-99 yield A in the table is the production amount of the energy region (40 → 20 MeV) obtained by the former target 11 alone, and the total milking amount B is the total obtained from Mo-99 produced by the former target 11 in one week. The value of the amount of Tc-99m (1st to 5th day), the single Tc-99m yield C is the production amount of the energy region (20 → 10 MeV) obtained by the latter stage target 12 alone, and the total Tc-99m yield D is The ratio of the value given by the sum (B + C) of the front stage target 11 and the rear stage target 12 and the single Tc−99m is (B + C) / C.

  As is clear from Table 1, with simple double irradiation without changing the rear stage target 12, the single Tc-99m yield C is saturated, and even when irradiated with 1 mA for 7 days, the total Tc-99m yield D remains at 543 Ci. On the other hand, in the case of the exchange irradiation according to the present invention, the yield of 2404Ci was almost 5 times as high. On the other hand, in the fast neutron method shown for reference, it was 171 Ci.

  FIG. 13 (disassembled perspective view) and FIG. 14 (front stage target) show the detailed configuration of the second embodiment of the present invention in which the rotary body of the front stage target portion 20 of the first embodiment is an opposed type of two rotary bodies 74A and 74B. Sectional view). In the figure, 28 is a sealing lid, 50 is a cooling nozzle for cooling the target, and 52 is a condenser.

  FIG. 15 shows a third embodiment of the present invention in which the rear stage target portion 40 of the first embodiment is a rotary type by a turret 43 that is rotationally driven by a motor 44.

  FIG. 22 shows a fourth embodiment of the present invention in which all targets are turret types and three stages of targets 11, 12, 13 are provided. In the figure, reference numeral 23 denotes a one-stage turret rotated by the motor 24, 80 denotes a three-stage turret section, and 83 denotes a three-stage turret rotated by the motor 84.

  In the above-described embodiment, the target 70 on the turbine type rotator 74 is provided perpendicular to the beam 10. However, as shown in the modification shown in FIG. You can also. When the beam is vertical, the distance that the beam 10 passes through the target 70 is only the thickness t as shown in FIG. 18 (A), whereas when the beam 10 is inclined, as shown in FIG. 18 (B). Since it becomes longer by 1 / sin θ and becomes L ′ = L × (1 / sin θ), even if an expensive target is made thinner, it can be irradiated in a pseudo-thickness, and the cost can be reduced.

  FIG. 19 shows the front target unit 20 of the fifth embodiment of the present invention in which the targets 11A and 11B are arranged obliquely as shown in FIG. 17 on the rotating bodies 74 and 74B that rotate in the opposite directions of the upper target.

  The method of tilting the target with respect to the beam is not limited to the method shown in FIG. 17, and the rotation shaft 72 of the rotating body 74 may be tilted with respect to the beam 10 as shown in FIG. 20.

  Next, FIG. 21 shows a sixth embodiment of the present invention in which the front stage target 11 and the rear stage target 12 are arranged together on the rotating body 74.

  In this embodiment, the rack and pinion gear may be continuously rotated counterclockwise in the figure, but as shown in FIGS. 22 (A), (B), and (C), the rack and pinion gear is constituted by a cylinder 90 composed of two cylinders. Thus, the three sets of targets 11 and 12 can be exchanged by causing the rotating body 74 to rotate intermittently. The targets 11 and 12 are composed of three groups, group 1, group 2 and group 3, and when the target group 1 stops at the direct irradiation position of the beam 10 as shown in FIG. One of the cylinders 90 is actuated and instantaneously rotates 120 degrees counterclockwise, and the group 2 stops at the direct irradiation position of the beam 10 as shown in FIG. Similarly, when the target group 2 is irradiated for the required time, the other of the cylinders 90 instantly operates and rotates again counterclockwise by 120 degrees, and the group 3 stops at the direct irradiation position of the beam 10 as shown in (C). And receive the necessary time. Each target after irradiation is appropriately replaced or removed at the non-irradiation position.

  The rotating body 74 can be exchanged as follows, for example. That is, a rubber grip 78 that is inwardly expanded by a fluid (for example) air pressure as shown in FIG. 23B is provided inside the rotating shaft holding portion 77 of the motor 76 shown in FIG. Then, as shown in FIG. 24, for example, the robot hand 66 holds the rotating body 74, and as shown in FIG. 25, the pneumatic pressure to the rubber grip 78 can be turned on and off.

  In the above description, two or more targets are provided, but the target may be one.

  The Mo-100 is arranged in the front stage to produce Mo-99 having a half-life of 66 hours, and the latter stage is similarly arranged to produce Tc-99m having a half-life of 6 hours. FIG. 26 shows a time chart of Example 1 in which different nuclides are obtained separately.

  Note that a shorter interval between beam irradiations is preferable because physical attenuation in the previous stage can be suppressed. For example, re-irradiation is possible in about 10 minutes. The reason for setting the irradiation time to a half-life of 6 hours is that the half-life irradiation of the production nuclide is effective in terms of yield. In addition, when it is not necessary to consider efficiency, irradiation time can be made arbitrary.

  In order to produce the third different nuclide (in this case, Zn-62) during the production of Mo-99 / Tc-99m, this is an example in which another target material (in this case, Cu) is irradiated. 100 is arranged to produce Mo-99 with a half-life of 66 hours, while Mo-100 and Cu-nat are alternately arranged in the latter stage to form a Tc-99m with a half-life of 6 hours and a Zu- with a half-life of 9 hours. FIG. 27 shows a time chart of the second embodiment in which 62 is generated alternately.

  There is a concern that emitting a continuous beam over a relatively long period of several days to one week may cause a large load on the production schedule of other nuclides. However, according to the present invention, for example, if the irradiation can be covered by a relatively short time irradiation, for example, if a long irradiation time is required, for example, a part of the targets arranged in the first stage may be It is not impossible to produce a third nuclide by using a target other than molybdenum.

  Mo-100 and Zn-68 are alternately placed in the previous stage so that the incident energy is uniform for each target, generating Mo-99 with a half-life of 66 hours and Cu-67 with a half-life of 62 hours for each sheet. Thus, FIG. 28 shows a time chart of Example 3 in which Mo-100 is arranged in the subsequent stage to generate Tc-99m having a half-life of 6 hours.

  As described above, two or more types of targets to be continuously irradiated may be used as long as the half-lives of the nuclides to be generated are similar and the beam energy ranges to be used are also equivalent. In this case, the arrangement of the targets 11A and 11B may be either FIG. 29A in which the same target is arranged for each rotator or FIG. 29B in which the target is changed even in the same rotator. The present embodiment is very effective as a method for efficiently using precious machine time.

  Time of Example 4 in which Zn-62 having a half-life of 9 hours was produced by arranging Cu-nat in the former stage and Tb-152g having a half-life of 5.3 days was produced by arranging Gd-152 in the latter stage. A chart is shown in FIG.

  Thus, contrary to Example 1-3, the former stage target may be exchanged for irradiation.

  Further, in each time chart shown in FIGS. 26 to 30, the irradiation end time of the last target of the target having a short half-life coincides with the irradiation end time of the target having a long half-life in order to effectively use the irradiation beam. Is set.

  In any case, the target / irradiation time / generated nuclide / beam type / exchange target / exchange time are not limited as long as the energy range and the half-life match the configuration intended by the present invention.

  Radionuclides such as molybdenum 99 and technetium 99m, which are in great demand as radiopharmaceuticals used in radiology, nuclear medicine, diagnostic imaging, etc., can be efficiently produced and supplied at low cost.

DESCRIPTION OF SYMBOLS 8 ... Accelerator 10 ... Beam 11, 11A, 11B, 12, 13, 14, 70 ... Target 20 ... Previous stage target part 34, 43, 83 ... Turret 24, 44, 84 ... Motor 40 ... Rear stage target part 50 ... Cooling nozzle 74 , 74A, 74B ... Rotating body 80 ... Three-stage target part

Claims (40)

  A method for producing a radionuclide using an accelerator, wherein a plurality of solid targets are replaced during beam irradiation.   The target is supported by the rotating body and rotates around an axis outside the beam trajectory, so that one target supported by the rotating body is in a heated state in which the beam is received and in a cooled state in which the beam is not received. The method for producing a radionuclide using an accelerator according to claim 1, wherein:   The method for producing a radionuclide using an accelerator according to claim 2, wherein the rotating body is intermittently rotated to stop the target one after another at an irradiation position for a predetermined time.   3. The method for producing a radionuclide using an accelerator according to claim 2, wherein the rotating body is reciprocally rotated.   The method for producing a radionuclide using an accelerator according to any one of claims 2 to 4, wherein the target is supported as a rotor blade on the outer periphery of the turbine-like rotor.   6. The method for producing a radionuclide using an accelerator according to claim 5, wherein the target is tilted with respect to a beam axis.   7. The radiation by an accelerator according to claim 2, wherein a plurality of the rotators are provided across the beam, and targets supported by the rotators are alternately in contact with the beam. A method for producing nuclides.   8. The method for producing a radionuclide using an accelerator according to claim 2, wherein the rotating body is rotated by a fluid used for cooling the target.   A part of the fluid used for cooling the target is guided to the inside of the rotating body and supplied to a target site via a flow path extending in the centrifugal force acting direction of the rotating body. A method for producing a radionuclide using the accelerator according to claim 8.   The method for producing a radionuclide using an accelerator according to any one of claims 2 to 4, wherein the target is supported on a rotation plane of a turret-like rotating body.   The method for producing a radionuclide using an accelerator according to any one of claims 2 to 10, wherein the periphery of the rotating body and the target is filled with a cooling medium. A plurality of solid targets arranged in series are irradiated with a beam of particles from the accelerator,
Each beam reacts with energy attenuated as the beam passes through the target,
The method for producing a radionuclide using an accelerator according to any one of claims 1 to 11, further comprising efficiently obtaining a plurality of nuclides having different half-lives by exchanging the target according to the irradiation time of the target.   The target that obtains the nuclide with the short half-life is sequentially continued until the irradiation of the target that obtains the nuclide with the long half-life is completed and collected until the target is obtained, or is stopped temporarily. The method for producing a radionuclide using an accelerator according to claim 12, wherein the radionuclide is exchanged and collected.   The method for producing a radionuclide using an accelerator according to claim 13, wherein the irradiation time until the exchange is 0.5 to 2.5 times the half-life of the production nuclide.   The method for producing a radionuclide using an accelerator according to any one of claims 1 to 14, wherein at least one material of the target is a metal and / or a metal oxide.   The method for producing a radionuclide using an accelerator according to any one of claims 12 to 15, wherein a plurality of nuclides having different half-lives are obtained separately from the target having the same chemical composition and / or isotope abundance ratio.   The method for producing a radionuclide using an accelerator according to claim 15 or 16, wherein the particles are protons and the target is molybdenum 100.   The method for producing a radionuclide using an accelerator according to claim 17, wherein the produced nuclides are molybdenum 99 and technetium 99m.   The radionuclide by an accelerator according to claim 18, wherein an incident energy of a proton used for manufacturing the molybdenum 99 is 60-20 MeV, or an incident energy of a proton used for manufacturing the technetium 99m is 30-20 MeV. Manufacturing method.   18. Production of a radionuclide by an accelerator according to claim 17, wherein the target molybdenum 100 is activated by recoil neutrons generated when protons collide, and as a result, molybdenum 99 and / or technetium 99m are produced. Method.   An apparatus for producing a radionuclide using an accelerator, comprising means for replacing a plurality of solid targets during beam irradiation.   The target is supported by the rotating body and rotates around an axis outside the beam trajectory, so that one target supported by the rotating body is in a heated state in which the beam is received and in a cooled state in which the beam is not received. The apparatus for producing a radionuclide using an accelerator according to claim 21, wherein   23. The radionuclide production apparatus using an accelerator according to claim 22, wherein the rotating body performs an intermittent rotational motion, and the target is stopped for a predetermined time one after another at the irradiation position.   23. The radionuclide production apparatus using an accelerator according to claim 22, wherein the rotating body is configured to perform reciprocating rotational motion.   The radionuclide production apparatus using an accelerator according to any one of claims 22 to 24, wherein the target is supported as a rotor blade on the outer periphery of a turbine-like rotor.   26. The radionuclide production apparatus using an accelerator according to claim 25, wherein the target is tilted with respect to a beam axis.   27. The apparatus for producing a radionuclide using an accelerator according to claim 22, wherein a plurality of the rotating bodies are provided with a beam interposed therebetween, and targets supported by the rotating bodies alternately hit the beam.   The radionuclide production apparatus using an accelerator according to any one of claims 22 to 27, wherein the rotator is rotated by a fluid used for cooling a target.   29. A part of a fluid used for cooling the target is guided to the inside of the rotating body and supplied to a target site via a centrifugal force of the rotating body. Radionuclide production equipment using an accelerator.   The method for producing a radionuclide using an accelerator according to any one of claims 22 to 24, wherein the target is supported on a rotation plane of a turret-like rotating body.   31. The radionuclide production apparatus using an accelerator according to claim 22, wherein the periphery of the rotating body and the target is filled with a cooling medium. A plurality of solid targets arranged in series are irradiated with a beam of particles from the accelerator,
Each beam reacts with energy attenuated as the beam passes through the target,
32. The radionuclide production apparatus using an accelerator according to claim 21, wherein a plurality of nuclides with different half-lives are efficiently obtained by exchanging the target according to the irradiation time of the target.   The target that obtains the nuclide with the short half-life is sequentially continued until the irradiation of the target that obtains the nuclide with the long half-life is completed and collected until the target is obtained, or is stopped temporarily. 33. The radionuclide production apparatus using an accelerator according to claim 32, which is exchanged and collected.   34. The radionuclide production apparatus using an accelerator according to claim 33, wherein the irradiation time until the exchange is about 0.5 to 2.5 times the half-life of the production nuclide.   The radionuclide production apparatus using an accelerator according to any one of claims 21 to 34, wherein at least one material of the target is a metal and / or a metal oxide.   36. The radionuclide production apparatus using an accelerator according to any one of claims 22 to 35, wherein a plurality of nuclides having different half-lives are separately obtained from the target having the same chemical composition and / or isotope abundance ratio.   37. The radionuclide production apparatus using an accelerator according to claim 35 or 36, wherein the particles are protons and the target is molybdenum 100.   38. The radionuclide production apparatus using an accelerator according to claim 37, wherein the produced nuclides are molybdenum 99 and technetium 99m.   39. The radionuclide by an accelerator according to claim 38, wherein an incident energy of a proton used for manufacturing the molybdenum 99 is 60-20 MeV, or an incident energy of a proton used for manufacturing the technetium 99m is 30-20 MeV. Manufacturing equipment.   38. The accelerator according to claim 37, wherein the molybdenum 100 as a target is activated by recoil neutrons generated when protons collide, and as a result, molybdenum 99 and / or technetium 99m are produced. Radionuclide production equipment by

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