Method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99, and purification and recovery system for medical technetium-99m from low specific activity molybdenum-99

Abstract

A radioactive pharmaceutical using low-specific-activity radioactive molybdenum-99 as a raw material and radioactive technetium-99m as a raw material for its labeled compound are extracted at a user point such as a hospital. Fill an activated carbon or alumina in a metal mesh cylindrical container that is not a column with restricted flow rate, make it in a low-pH acidic state, and immerse the metal mesh cylindrical container in the molybdenum solution that is flowing by stirring to adsorb the molybdenum-99 onto the activated carbon or alumina to prepare a molybdenum-99 adsorption column. Elute the technetium-99m generated from the molybdenum-99 from the molybdenum-99 adsorption column, and pass it through a technetium-99m purification column filled with aluminum oxide to capture the technetium-99m. Pass a pH-neutral physiological saline through the technetium-99m purification column to separate and elute the technetium-99m, remove impurities, and then purify and recover it.

Description

Technical Field

[0001] The present invention relates to a radiopharmaceutical using low-specific-activity radioactive molybdenum-99 ( 99 Mo) as a raw material and a process for extracting radioactive technetium-99m ( 99m Tc) at a user point such as a hospital as a raw material for its labeled compound, and a system therefor.

Background Art

[0002] Tc (technetium) is a transition metal with an atomic number of 43 located in Group 7 and Period 5. Among the isotopes of Tc, 99m Tc (technetium-99m) emits only γ (gamma) rays with a short half-life (6 hours) suitable for diagnostic imaging and weak energy (140 keV) suitable for in vitro measurement, and furthermore 99 using a generator ( 99 Mo / 99m Tc generator) utilizing the radioactive equilibrium with 99m Mo, it is widely used in nuclear medicine diagnostic imaging. 99 Tc, due to its short half-life, usually obtains its parent nuclide 99 Mo (half-life 66 hours), and is used in the method of obtaining 99m Tc from

[0003] 99 As a method for obtaining 235 Mo, the specific activity (the intensity of radioactivity per unit mass of a substance containing a radioactive isotope) produced by the nuclear fission method using neutron irradiation of fissile uranium ( 99 U; uranium) is very high 99 Mo is generated, and at the same time, the Fission method (nuclear fission method) of separating and using it from the simultaneously generated nuclear fission products has been used worldwide as a practical technology. In that case, 99 since the specific activity of 99 Mo is high, generally using aluminum oxide (alumina) used in medicine as its adsorbent, carrying99 Daughter nuclide of Mo 99m By eluting (milking) Tc with physiological saline 99m The method of obtaining Tc is used as an actual manufacturing technique.

[0004] On the other hand, 99 Without using uranium as a raw material for obtaining Mo, using a molybdenum compound as a raw material, and containing it as one of its isotopes 98 By utilizing the neutron activation (n,γ) reaction of Mo (a neutron capture reaction in which a substance irradiated with neutrons undergoes a nuclear reaction and emits γ-rays when it changes into a radioactive substance), the target 99 There is a method for generating Mo, and the Mo generated by this (n,γ) method 99 Compared with the Fission method, the 99 Specific activity of Mo is extremely low, about one ten-thousandth (hereinafter, low specific activity is referred to as LSA). Therefore, in order to put the (n,γ) method into practical use, trace amounts of 99 Daughter nuclide generated from Mo, trace amounts of 99m Tc need to be separated, purified, and recovered.

[0005] So far, as methods studied and put into practical use as the (n,γ) method, the activated carbon method, the sol-gel method, the MEK method, and the sublimation method are known. These methods are for a large amount of 99m Tc in a pharmaceutical manufacturer's factory for preparations such as Tc-labeled compounds used in diagnosis 99 Extraction method of a large amount of 99m Tc from Mo. On the other hand, at user points such as hospitals, for individuals or a few patients, the 99m Tc needed on that day is often extracted, recovered, and used.

[0006] Instead of Mo with high specific activity using uranium as a raw material, low specific activity LSA 99 Mo using a molybdenum compound as a raw material 99 Is used 99mAlthough the development of Tc small generators (TcPG: Technetium-99m portable generators) has been carried out many times so far, they have not been put into practical use for the reasons shown below. The inventors of the present invention developed and proposed a PZC (polyzirconium compound) method, which is a kind of sol-gel method.

[0007] In Patent Document 1, radioactive molybdenum, which is the parent nuclide of technetium 99 Mo, is neutron-irradiated in a nuclear reactor using natural isotope Mo as a raw material, so that 98 it is generated by the Mo(n,γ) reaction, and 99 a Mo solution containing Mo is passed through an activated carbon (AC) column, so that 99 Tc, which is the daughter nuclide of Mo, 99m is selectively adsorbed and collected on the AC, and the activated carbon non-adsorbed Mo ( 99 containing Mo) remaining in the voids of the AC column and the pores of the AC is washed away with water. Then, the Tc adsorbed on the AC is eluted using an alkali (such as caustic soda NaOH) solution, and further, 99m Mo, 99m Mo, radioactive impurities, and other impurities contained in the Tc recovery solution are removed by passing the solution through an aluminum oxide (alumina)-filled AL column arranged at the rear stage of the AC column, 99 so as to purify the Tc recovery solution. A method and apparatus for this are described. 99m 99m

[0008] In Patent Document 2, similar to Patent Document 1, natural isotope Mo is neutron-irradiated in a nuclear reactor to generate 98 Mo by the Mo(n,γ) reaction, and then 99 Tc, which is the daughter nuclide of Mo, 99m is recovered using spherical activated carbon (BAC), 99m a method for recovering Tc, 99 a Mo solution containing Mo is passed through an AC column by a pressure flow in which the solution is pumped into the column or a vacuum flow in which the solution is sucked into the column by a pump, and the activated carbon non-adsorbed Mo ( 99 containing Mo) remaining in the voids of the AC column and the pores of the AC is washed away with water. Then, the Tc adsorbed on the AC is eluted using an alkali (such as caustic soda NaOH) solution, and after that,99m As a method for eluting Tc from AC, a method of heating to about 80 °C to promote elution was investigated. Then, 99m Mo contained in the Tc recovery solution, 99 Mo, radionuclides, and other impurities are removed by passing through a column filled with AL arranged at the rear stage of the AC column, 99m A method and apparatus for purifying the Tc recovery solution are described.

[0009] In Patent Document 3, as in Patent Documents 1 and 2, by neutron irradiation of natural isotope Mo in a nuclear reactor, 98 Generated by the Mo(n,γ) reaction 99 From Mo to its daughter nuclide 99m Tc is recovered using AC. Mainly, 99 To prevent leakage of radioactive substances by shielding radiation such as γ-rays emitted from Mo, it is installed inside a double-walled cell 99 Piping from a Mo solution tank containing Mo to an external cell equipped with an AC column with low radiation shielding ability, circulating the Mo solution through the AC column installed in the external cell and then back to the internal Mo solution tank, 99m To selectively adsorb and collect Tc to prevent external radiation leakage. Then, after washing away the activated carbon non-adsorbable Mo ( 99 Mo-containing) in the voids of the AC column and the pores of the AC with water, 99m Tc adsorbed on the AC is eluted using an alkaline (such as caustic soda NaOH) solution, and finally, 99m Mo contained in the Tc recovery solution, 99 Mo, radionuclides, and other impurities are removed by passing through a column filled with AL arranged at the rear stage of the AC column, 99m A method and apparatus for purifying the Tc recovery solution are described.

[0010] The PZC method described in Patent Documents 4 to 6 is an inorganic polymer compound (polyzirconium compound) composed of zirconium (Zr)-oxygen (O)-chlorine (Cl), and by Zr-O-Mo bonds 99Those containing Mo bind 200 - 250 mg(Mo) / g(PZC) of Mo per unit weight of PZC, 99 Mo- 99m which are the basic characteristics of a 99m Tc generator. Moreover, the

[0011] Tc milking characteristics are also excellent. However, since the constituent components of PZC contain the heavy metal zirconium, it is judged that it is difficult to apply for a change in radioactive pharmaceutical standards, and thus practical application has not progressed.

[0012] Patent Document 7 is similar. As a matrix enabling the elution of technetium 99m, molybdenum compounds containing molybdenum 99 selected from the group consisting of zirconium molybdate, titanium molybdate, cerium molybdate, iron molybdate, tin molybdate, and mixtures thereof are used. Since all of them contain heavy metals such as Zr (zirconium), Ti (titanium), Ce (cerium), Fe (iron), Sn (tin), etc., it is considered that it is difficult to apply for a change in radioactive pharmaceutical standards and practical application has not progressed. 99 When alcohol such as ethanol, propanol, or isopropyl alcohol is used as a precipitant in an 99 Mo solution, 99% of 99m Mo precipitates and is easily recovered. A method for recovering and purifying the daughter nuclide 99m Tc in the solution is described. However, in this method, at the use point such as a hospital, 99 Tc cannot be used as a small 99m Mo /

Prior Art Documents

Patent Documents

[0013]

Patent Document 1

Patent Document 2

Patent Document 3

[0014] The prior arts described in Patent Documents 1 to 3 99 In order to recover Tc generated in a Mo solution containing Mo 99m inside a metal cylindrical container (column) where the inflow part and the outflow part of the Mo solution are connected, 99m activated carbon (AC) capable of selectively adsorbing Tc is filled and built in, and the Mo solution is passed through the column.

[0015] In the conventional method, in order to completely adsorb and collect Tc contained in the Mo solution by passing it through the AC column, 99m it is necessary to limit the flow rate when flowing a Mo( 99 Mo) solution( 99 Mo solution containing Mo) through a flow-through AC column. Specifically, in the case of a low specific activity Mo solution, 99 since the Mo concentration is low, in order to recover the target amount of 99m Tc, it is necessary to pass a large amount of Mo( 99 Mo) solution through the AC column. For example, when the flow rate per unit time passed through an AC column filled with 5 g of AC is a maximum of 50 to 100 mL / min, 99 it takes 20 to 40 minutes or more to pass 2.0 L of Mo( 99m Mo) solution. There is a problem with work efficiency in recovering short half-life Tc for diagnostic use in a short time.

[0016] However, when the amount of the Mo( 99 Mo) solution becomes, for example, 5 to 20 L, 99m the time required to pass the solution through the AC column to adsorb and collect Tc becomes 2 to 5 hours or more, the working efficiency decreases, and the short half-life 99m Tc recovered may deteriorate 99g into Tc and may become unusable as a pharmaceutical raw material. Incidentally, 99g Tc (technetium 99 ground state) is 99m one of the radioactive isotopes of Tc with a half-life of 211,000 years generated from Tc and is a pharmaceutical raw material 99m Tc is generated in proportion to the elapsed time after the extraction and separation of Tc, and if there is too much, it becomes an impurity of the pharmaceutical raw material 99m Tc.

[0017] From a high-concentration Mo solution containing radioactive molybdenum 99( 99 Mo) as a radioactive pharmaceutical raw material, in the high-concentration Mo solution 99 generated and contained by the decay of Mo 99 technetium 99m( 99m Tc), which is the daughter nuclide of Mo, in order to recover it, even if there is 10 16 or more Mo( 99 Mo) in terms of the atomic number ratio, it is sufficient to use AC that can selectively adsorb and recover the trace amount of 99m Tc therein.

[0018] In the high-concentration Mo solution formed 99 daughter nuclide of Mo 99m As a method for selectively separating and recovering Tc, if a metal mesh cylindrical container with AC built-in is immersed in the Mo solution and the surrounding Mo solution is stirred and flowed to adsorb and collect Tc in the Mo solution, there is no need to pass the solution through an AC column that requires a flow rate limit. That is, if Tc contained in the Mo solution is adsorbed and collected by the AC immersed in the Mo solution, it is not necessary to take a long time by passing the solution through the AC column. 99m Tc 99m Tc in the Mo solution can be adsorbed by the AC immersed in the Mo solution and collected, and it is not necessary to take a long time by passing the solution through the AC column.

[0019] Also, at the use point such as a hospital, in a short time 99mIn order to enable the diagnosis by milking (eluting and recovering) Tc, highly non-radioactive 99 Mo supported on alumina has been used so far. However, 99m Since the parent nuclide of Tc, 99m Mo, is produced using enriched uranium as a raw material, there are problems related to nuclear safety and 99 the problem of high-level nuclear fission waste generated and accumulated during Mo production. Furthermore, 99 Mo production depends on irradiation reactors localized in Europe, South Africa, Australia, etc., and since these reactors are aging, frequent operation troubles and transportation troubles have led to 99 frequent disruptions in Mo production and supply, 99 hindering Tc medical diagnosis. 99m It has problems such as this.

[0020] For the Mo raw material, 98 In the Mo(n,γ) 99 reaction, the radioactive concentration of the generated 99 Mo is as low as 1 / 10,000 compared to the case of using uranium as a raw material. Therefore, for the low specific activity LSA used at user points such as hospitals, 99 Mo / 99m Tc small generators have not been put into practical use yet. As in the prior art described in Patent Documents 4 to 8, conventional LSA 99 Mo / 99m Tc small generators have not been put into practical use in some cases because heavy metals such as Zr and Ti are used as Mo adsorbents.

[0021] Molybdate ions in an Mo aqueous solution, such as water-soluble Mo compounds like Na2MoO4 and (NH4)2MoO4, have low adsorbability to activated carbon at neutral to alkaline pH, while Tc is adsorbed by activated carbon. On the other hand, at low pH (for example, acidic around pH 1 to 5), Mo forms a higher oxide structure of Mo6O 21 6- and has the property of being adsorbed and retained in large amounts by activated carbon and alumina in the state of Mo oxide with a high volume density.

[0022] Therefore, an object of the present invention is to provide a method for extracting technetium-99m from molybdenum-99 with low specific radioactivity in a short time without being affected by the amount of the molybdenum solution.

[0023] Another object of the present invention is to provide a small generator capable of extracting technetium-99m as a radioactive pharmaceutical using low specific radioactivity radioactive molybdenum-99 as a raw material and as a raw material for its labeled compound at a use point such as a hospital.

Means for Solving the Problems

[0024] In order to solve the above problems, the method for recovering technetium-99m from low specific radioactivity molybdenum-99 according to the present invention is a method for separating and recovering daughter nuclide technetium-99m generated by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing molybdenum-99 with low specific radioactivity, using activated carbon, wherein the activated carbon is filled in a metal mesh cylindrical container that is not a column with a restricted flow rate, and is immersed in the molybdenum solution that is flowing by stirring, so as to selectively adsorb trace amounts of technetium-99m therein, which is characterized by this.

[0025] In the method for recovering technetium-99m from the low specific radioactivity molybdenum-99, the molybdenum solution contains radioactive nuclide molybdenum-99 generated by the neutron capture (n,γ) reaction of natural isotope molybdenum, which is characterized by this.

[0026] In addition, the method for producing an aqueous physiological saline solution containing technetium-99m according to the present invention is characterized in that molybdenum remaining in the pores of activated carbon adsorbed with technetium-99m recovered by the method for recovering technetium-99m from the low-specific-activity molybdenum-99 is washed with water, and a solution containing technetium-99m eluted from the activated carbon with an alkaline solution is passed through an IER column filled with a strongly acidic cation exchange resin to remove alkaline components, and then passed through an AL column filled with alumina to capture technetium-99m, and technetium-99m is eluted from the AL column using physiological saline, thereby purifying it into an aqueous physiological saline solution containing technetium-99m from which impurities have been removed.

[0027] In the method for producing an aqueous physiological saline solution containing technetium-99m, the container for housing the activated carbon, the IER column, and the AL column are made of a material that can be autoclaved and sterilized.

[0028] Furthermore, the recovery system for technetium-99m from natural molybdenum according to the present invention includes means for generating a high-concentration molybdenum solution containing molybdenum-99 with low specific activity generated by the neutron capture (n,γ) reaction of natural isotope molybdenum, means for generating daughter nuclide technetium-99m by the decay of molybdenum-99 in the molybdenum solution, means for filling activated carbon in a metal mesh cylindrical container that is not a column with a restricted flow rate and immersing the activated carbon in the flowing molybdenum solution by stirring, means for washing the remaining molybdenum-99 from the activated carbon adsorbed with technetium-99m with water, means for eluting technetium-99m from the washed activated carbon using an alkaline solution and passing the eluate through a strongly acidic cation exchange resin column to remove alkaline components, and then passing the resulting solution through an alumina column to capture technetium-99m, and means for eluting technetium-99m from the alumina column using physiological saline and recovering the purified technetium-99m.

[0029] In order to solve the above-mentioned another problem, the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention is a method for separating and recovering daughter nuclide technetium-99m generated by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low-specific-activity molybdenum-99. Activated carbon or alumina is filled in a metal mesh cylindrical container that is not a column with restricted flow rate. After making it in a low-pH acidic state, the metal mesh cylindrical container is immersed in the flowing molybdenum solution by stirring to adsorb the molybdenum-99 on the activated carbon or alumina, thereby preparing a molybdenum-99 adsorption column. The technetium-99m generated from the molybdenum-99 is eluted from the molybdenum-99 adsorption column and passed through a technetium-99m purification column filled with weakly acidic alumina to capture the technetium-99m. The technetium-99m is separated and eluted by passing pH-neutral physiological saline through the technetium-99m purification column to remove impurities and then purified and recovered. This is the feature.

[0030] Also, the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention is a method for separating and recovering daughter nuclide technetium-99m generated by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low-specific-activity molybdenum-99. The molybdenum solution in a low-pH acidic state is circulated through a column container filled with activated carbon or alumina to adsorb the molybdenum-99 on the activated carbon or alumina, thereby preparing a molybdenum-99 adsorption column. The technetium-99m generated from the molybdenum-99 is eluted from the molybdenum-99 adsorption column and passed through a technetium-99m purification column filled with weakly acidic alumina to capture the technetium-99m. The technetium-99m is separated and eluted by passing pH-neutral physiological saline through the technetium-99m purification column to remove impurities and then purified and recovered. This is the feature.

[0031] Also, in the method for purifying and recovering medical technetium-99m from the low-specific-activity molybdenum-99, the molybdenum solution contains radioactive nuclide molybdenum-99 generated by the neutron capture (n,γ) reaction of natural isotope molybdenum, which is characterized by this.

[0032] Also, in the method for purifying and recovering medical technetium-99m from the low-specific-activity molybdenum-99, the amount of the activated carbon or alumina for adsorbing the molybdenum-99 is increased or decreased according to the specific-activity concentration of the molybdenum-99, and the concentration of the technetium-99m separated and eluted from the molybdenum-99 is changed, which is characterized by this.

[0033] Furthermore, the purification and recovery system for medical technetium-99m from the low-specific-activity molybdenum-99 according to the present invention includes means for generating a high-concentration molybdenum solution containing low-specific-activity molybdenum-99 generated by the neutron capture (n,γ) reaction of natural isotope molybdenum, means for creating a molybdenum-99 adsorption column in which the molybdenum solution is brought into a low-pH acidic state and the molybdenum-99 is adsorbed onto activated carbon or alumina, means for generating daughter nuclide technetium-99m by the decay of the molybdenum-99, means for eluting the technetium-99m from the molybdenum-99 adsorption column and capturing the technetium-99m by passing it through a technetium-99m purification column filled with weakly acidic alumina, and means for separating and eluting the technetium-99m by passing pH-neutral physiological saline through the technetium-99m purification column, removing impurities, and then purifying and recovering it, which is characterized by this.

[0034] Furthermore, the molybdenum-99 adsorption column according to the present invention has activated carbon or alumina filled in a metal mesh cylindrical container that is not a column with a restricted flow rate, and after bringing it into a low-pH acidic state, the metal mesh cylindrical container is immersed in the flowing molybdenum solution by stirring to adsorb the molybdenum-99 onto the activated carbon or alumina, which is characterized by this.

Advantages of the Invention

[0035] According to the present invention, a high-concentration Mo solution containing radioactive 99 Mo is generated and left standing for about 24 hours, so that 99 Tc is generated from 99m Mo and is in a state of being mixed in radioactive equilibrium (the ratio of the radioactivity of the parent nuclide to the daughter nuclide is constantly balanced). Instead of passing the solution through an AC column as in the prior art, an AC-filled metal mesh cylindrical container is immersed in the stirring and flowing Mo solution, so that 99m Tc can be adsorbed and captured by the AC at all times.

[0036] Whether the amount of the high-concentration Mo solution is small, for example, 0.1 L, or large, such as 5 to 20 L, 99 Tc is generated from 99m Mo and reaches radioactive equilibrium, or at the time when the desired 99m Tc amount is generated, the target amount of 99m Tc is selectively adsorbed and collected by the AC. Therefore, it is particularly effective for the recovery of 99m Tc with a short half-life (6 hours).

[0037] When desorbing the 99m Tc adsorbed and collected by the AC in the metal mesh cylindrical container, the Mo ([[]] 99 Mo) that remains non-adsorbed by the AC also [[[]] 99m dissolves and elutes simultaneously with 99m Tc. However, by passing the 99 Tc recovery solution through an alumina column, high-purity 99m Tc can be purified and recovered as a pharmaceutical raw material without contamination by radioactive impurities such as Mo ([[]] 99 Mo).

[0038] In addition, the 99 Mo production method according to the present invention uses molybdenum with a natural isotope ratio without using enriched uranium as a raw material. It is one of the Mo isotopes naturally contained at 24.1%, namely 98 Mo is produced by neutron activation of 98 Mo through the 99 Mo(n,γ) reaction.

[0039] According to the present invention, it is possible to realize a small generator capable of extracting radioactive technetium-99m as a radioactive pharmaceutical and a raw material for its labeled compound using radioactive molybdenum-99 with low specific radioactivity at a use point such as a hospital. Under acidic (pH 1 to 5) conditions, Mo (molybdenum-99) is adsorbed on AC (activated carbon) or AL (alumina) at about 1 g (Mo) / 5 g (AC or AL), and Tc (technetium-99m) elutes without adsorbing to Mo (molybdenum-99) laminated on AC or AL. By utilizing this property, a practical LSA 99 Mo / 99m Tc portable generator (TcPG) is obtained.

[0040] For the Mo raw material 98 Mo(n,γ) 99 In the Mo reaction, there is also a drawback that the radioactivity concentration of the generated 99 Mo is extremely low compared to the case of using uranium as a raw material, and in the LSA 99 Mo / 99m In the Tc small generator, heavy metals such as Zr and Ti were used as Mo adsorbents, so its practical application did not progress. However, in the present invention 99 Mo adsorption column and 99m Since no heavy metals are used in the configuration of the TC collection and concentration AL column, it can be approved with a minor pharmaceutical change application.

Brief Description of the Drawings

[0041]

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Embodiments for Carrying Out the Invention

[0042] 99 Instead of passing the Mo solution containing Mo through an AC column, 99m Rather than recovering Tc, a cylindrical metal (e.g., stainless steel, etc.) mesh container filled with AC is 99 constantly immersed in the Mo solution tank, and the Mo solution in which the AC container is immersed is stirred and made to flow, so that the AC is always 99m put in a state where it can adsorb Tc.

[0043] At a predetermined or arbitrary timing, the AC container is withdrawn from the Mo solution, and the AC non-adsorbable 99 Mo remaining in the AC pores is washed and removed with water, and then 99m the AC on which Tc is adsorbed is treated with an alkaline solution, so that the 99m Tc collected by the AC is eluted, and the solution is purified with a strongly acidic cation exchange resin (IER) and alumina (AL) to recover high-purity 99m Tc.

[0044] Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. Note that 99m Tc is the radionuclide technetium 99m, 99 and Mo is the radionuclide molybdenum 99. 99 Mo is the parent nuclide, 99m and Tc is in the relationship of the daughter nuclide. AC is activated carbon, IER is an ion exchange resin, and AL is alumina (aluminum oxide).

[0045] FIGS. 1 and 3 are diagrams showing a method for extracting technetium 99m from low-specific-activity molybdenum 99, a method for producing a physiological saline aqueous solution containing technetium 99m using that method, and a recovery system for technetium 99m from natural molybdenum. 99 Instead of the method of passing a Mo solution containing Mo through an AC column, in an AC-filled metal mesh cylindrical container, 99m Tc in the Mo solution is adsorbed and collected, 99m and Tc is purified and recovered.

[0046] Figure 2 is a diagram showing a method of passing a conventional molybdenum solution through an activated carbon column. Figure 4 is a diagram comparing the processes of the method for extracting technetium 99m from low-specific-activity molybdenum 99 of the present invention and the conventional method. Figure 5 is a diagram showing the process conditions for short-time production of a method for producing an aqueous physiological saline solution containing technetium 99m.

[0047] In the method for extracting technetium 99m from low-specific-activity molybdenum 99, daughter nuclide technetium 99m generated by the decay of molybdenum 99 contained in a high-concentration molybdenum solution containing low-specific-activity molybdenum 99 is separated and recovered with activated carbon.

[0048] The activated carbon is filled in a metal mesh cylindrical container that is not a column with a restricted flow rate, immersed in a flowing molybdenum solution by stirring, and selectively adsorbs trace amounts of technetium 99m therein even when the atomic ratio of molybdenum is 10 16 or more. The molybdenum solution contains radionuclide molybdenum 99 generated by the neutron capture (n,γ) reaction of natural isotope molybdenum.

[0049] In the method for producing an aqueous physiological saline solution containing technetium 99m, the molybdenum remaining in the pores of the activated carbon adsorbed with technetium 99m recovered by the method for recovering technetium 99m from low-specific-activity molybdenum 99 is washed with water, and the solution containing technetium 99m eluted from the activated carbon with an alkaline solution is passed through an IER column filled with a strongly acidic cation exchange resin to remove the alkaline component. Further, it is passed through an AL column filled with alumina to capture technetium 99m, and technetium 99m is eluted from the alumina column with physiological saline to purify it into an aqueous physiological saline solution containing technetium 99m from which impurities have been removed.

[0050] A technetium-99m recovery system from natural molybdenum comprises means for generating a high-concentration molybdenum solution containing molybdenum-99 with low specific radioactivity generated by the neutron capture (n,γ) reaction of natural isotope molybdenum, means for generating daughter nuclide technetium-99m by the decay of molybdenum-99 in the molybdenum solution, means for filling activated carbon in a metal mesh cylindrical container that is not a column with restricted flow rate and immersing the activated carbon in the flowing molybdenum solution by stirring, means for washing the remaining molybdenum-99 from the activated carbon adsorbed with technetium-99m with water, means for eluting technetium-99m from the washed activated carbon using an alkaline solution, passing the solution after removing the alkaline component through a strongly acidic cation exchange resin column, and then passing the solution through an alumina column to capture technetium-99m, and means for eluting technetium-99m from the alumina column using physiological saline and recovering the purified technetium-99m.

Example

[0051] As shown in FIG. 1, a tank 100 storing a Mo solution is installed in a hot cell for shielding radiation because the radiation dose of Mo is high. Inside the Mo solution tank 100, a stirrer 110 is provided as a function for stirring the solution, and a support 130 for holding a metal mesh cylindrical container 120 containing AC in the solution is also provided. A plurality of tanks 100 may be installed in the hot cell. 99 Since the radiation dose of Mo is high, it is installed in a hot cell for shielding radiation. Inside the Mo solution tank 100, a stirrer 110 is provided as a function for stirring the solution, and a support 130 for holding a metal mesh cylindrical container 120 containing AC in the solution is also provided. A plurality of tanks 100 may be installed in the hot cell.

[0052] Radioactive pharmaceutical raw material 99m To generate Tc, a radioactive nuclide 99 Mo-containing Mo solution, as Na2 99 MoO4 solution is supplied to the tank 100. When natural isotope MoO3 is irradiated with neutrons in a nuclear reactor in advance, 99 Mo is generated. 99 When MoO3 containing Mo is dissolved in an alkaline (NaOH) solution, a pH-neutral Na2 99 MoO4 solution is obtained.

[0053] Radioactive 99The Mo solution containing Mo is, for example, a high-concentration Mo solution containing 500 g of Mo (750 g as MoO3) in 2 L. To obtain about 500 Ci (curie) of 99m Tc, a high-concentration Mo solution containing 500 g of Mo in 2 L is required, but a high-concentration Mo solution containing 50 g of Mo (75 g as MoO3) in 200 mL, which is one-tenth of that amount, or a large amount of high-concentration Mo solution containing 5 kg of Mo (7.5 kg as MoO3) in 20 L, which is 10 times the amount, may also be used.

[0054] 99 Into the tank 100 containing the Mo solution containing Mo, a metal mesh cylindrical container 120 containing AC is placed, and it is held in the Mo solution by a support 130, and the Mo solution is stirred using a stirrer 110 or the water flow of a circulation pump. By maintaining this state, 99m Tc generated in the Mo solution is adsorbed and collected by the AC.

[0055] 99 Tc generated from Mo 99m becomes in a radioactive equilibrium state in about 24 hours. Therefore, after waiting for the elapse of that time, the metal mesh cylindrical container 120 may be lifted out of the Mo solution, or it may be lifted out at any timing before reaching the radioactive equilibrium. From the time when the metal mesh cylindrical container 120 is immersed in the Mo solution until it is lifted out, 99m Tc can be adsorbed by the AC.

[0056] As shown in FIG. 2, the conventional TcMM (technetium-99m master milker) is a method of passing the entire amount of the Mo solution through an AC column in order to adsorb 99m Tc in the Mo solution onto the AC. The AC column is a cylindrical container filled with AC, and the liquid passes through the inside of the cylinder from the inlet to the outlet while contacting the AC. With this method, since the flow rate of the Mo solution passing through the AC column is limited, the ability of the AC column to process the Mo solution is limited, and there is a problem as a 99m Tc recovery technique with a short half-life (lifetime).

[0057] As shown in FIG. 3, from the low-specific-activity Mo solution99m The system for highly concentrating, purifying, and recovering Tc is installed in a hot cell 140 isolated by a thick shielding wall to shield high radiation. In advance, 99 dissolve MoO3 with an alkali to 99 generate a MoO3 solution. Supply the MoO3 solution to a storage tank 100 with a capacity of 1 - 20 L provided in plurality in the hot cell 140 to 99 store a high - concentration Mo solution with a radioactivity of 500 Ci of Mo. 99

[0058] Put a metal - mesh cylindrical container 120 containing AC into the tank 100 using a hook and a carrier, etc., and hold it in a Mo solution containing Mo with a support 130. Note that due to the decay of radioactive 99 Mo, it changes to 99 Tc, and 99m a Mo solution containing Tc is obtained. 99m

[0059] When the metal - mesh cylindrical container 120 is impregnated with the Mo solution, it is advisable to stir the Mo solution with a stirrer 110 to efficiently bring the Mo solution into contact with AC. Tc generated in the Mo solution is adsorbed and collected by AC. Pull up the metal - mesh cylindrical container 120 from the tank 100 and 99m recover the AC adsorbed with Tc. Then, by containing the AC in a column and washing it with water, 99m Mo and the like that remain non - adsorbed on the AC are washed away. 99

[0060] Supply an alkali (NaOH) solution to the AC - containing column while adjusting the flow rate and temperature and let it flow through. By treating with the alkali solution, Tc elutes from the AC into the alkali solution, and the 99m alkali solution containing Tc discharged is passed through an IER column 150. In the IER column 150, the alkali component is captured by a strongly acidic cation - exchange resin, and the 99m solution containing Tc discharged is passed through an AL column 160. 99m

[0061] In the AL column 160, 99m ​​​​Tc is captured and impurities are discharged. Then, by passing a physiological saline solution with an NaCl concentration of about 0.9% through the AL column 160, 99m Tc elutes from the alumina into the physiological saline solution. 99m Since it becomes a TcO4 solution and is discharged together with the physiological saline solution, it is recovered as a physiological saline aqueous solution containing highly purified 99m Tc, which serves as a raw material for radiopharmaceuticals and labeled compounds.

[0062] Regarding the waste and waste liquid generated in the process of purifying and recovering high-purity 99m Tc from a high-concentration Mo solution, the radioactivity attached to them can be naturally attenuated to a low level and then solidified treatment can be performed. Accordingly, a space for storing and accommodating various radioactive and non-radioactive wastes and the like generated therewith may be provided in a hot cell 140 or the like.

[0063] For the container for accommodating AC (the metal mesh cylindrical container 120, the AC accommodation column for washing AC with water), the IER column 150, and the AL column 160, it is preferable to use a material and contents (AC, IER, AL) that can be sterilized by an autoclave (121 °C, 2 atm).

[0064] As shown in FIG. 4, the conventional method is compared with the process of the present invention. The conventional method is a flow-type TcMM that adsorbs and collects 99m Tc contained in the Mo solution by passing the Mo solution through an AC column. In the present invention, instead of passing the Mo solution through an AC column, the metal mesh cylindrical container 120 containing and incorporating AC is immersed in the flowing high-concentration Mo solution, so that 99m Tc generated in the Mo solution is adsorbed by the AC, which is an improved batch-type TcMM.

[0065] In the conventional method, in order to completely adsorb and collect 99m Tc contained in the Mo solution by passing the Mo solution through an AC column, it was necessary to provide a flow rate limit in the AC column for flowing the Mo solution. Specifically, in the case of a low specific activity Mo solution, 99 since the concentration of Mo is low, the target amount of 99mIn order to recover Tc, it is necessary to pass a large amount of Mo solution through an AC column. For example, when the flow rate per unit time through the AC column is maximally 50 to 100 mL / min, to pass 2.0 L of Mo solution, it takes 20 to 40 minutes or more, and for 99m Tc with a short half-life, the working efficiency is not good for recovering it for diagnostic use in a short time.

[0066] Moreover, in the case of a low-concentration Mo solution, because it becomes a lower-concentration 99m Tc, 99m when adsorbing and collecting 99m Tc with AC in the AC column, a larger amount of Mo solution needs to be passed through the AC column. For example, when the amount of Mo solution becomes 5 to 20 L, it takes 2 to 5 hours or more to pass it through the AC column, and there is a risk that the recovered 99g Tc deteriorates and becomes

[0067] 99 Tc, making it unusable as a pharmaceutical raw material. On the other hand, in the present invention, the AC accommodated in the metal mesh cylindrical container 120 can selectively separate and recover trace amounts of 99 Tc, which is the daughter nuclide generated by the decay of 99m Mo, even when the atomic number ratio of 99 Mo to 16 Tc is 10 99m or more in a high-concentration Mo solution containing radioactive

[0068] By immersing the metal mesh cylindrical container 120 with AC built therein in the Mo solution and stirring the Mo solution to make it flow around the metal mesh cylindrical container 120, 99m Tc in the Mo solution is more likely to be adsorbed by the AC. There is no need to adjust the flow rate of the Mo solution for passing it through the AC column, and 99m Tc is always adsorbed by the AC from the entire Mo solution existing around the metal mesh cylindrical container 120, so it becomes possible to collect 99m Tc in a short time.

[0069] As shown in FIG. 5, immerse the metal mesh cylindrical container 120 with AC accommodated and built therein in the Mo solution, 99mPurified from AC that had adsorbed and collected Tc as a pharmaceutical raw material 99m The time required for each step of recovering Tc is significantly shorter than the conventional method. Regardless of the amount of Mo solution and 99 regardless of the radioactivity of Mo, AC always 99m adsorbs and collects Tc, so the process time required for that is zero. After that, the time to purify and recover Tc from AC is about 10 minutes, and since it can always be operated in the same process for a fixed time, it is the optimal method as a pharmaceutical raw material manufacturing technology that requires strict quality and shipping status. 99m

Example

Example

[0070] 3,750 g of MoO3 containing a very large amount of Mo (2,500 g) was dissolved in 6 M (molar concentration mol / L) NaOH (1.75 - 1.8 L), and then H2O was added to prepare a Mo solution (10 L) with a pH of 8 - 9. The Mo solution was placed in a 15 L beaker, 99m 0.1 mg of Re (rhenium) was added as a substitute element for Tc (500 Ci), and a stainless steel wire mesh cylindrical container (diameter 1.6 cm, length 6 cm, volume 12 cc) filled with AC (4.5 g) was immersed in the Mo solution, and the rotating blade of a stirrer was rotated (30 rpm) in the Mo solution for 6 hours to stir. After stirring, the wire mesh cylindrical container was taken out from the Mo container (the container containing the Mo solution), washed with water to wash away the Mo remaining non-adsorbed in the pores of the AC, and 1.3 M NaOH (30 mL) was used to elute the Re adsorbed on the AC from the AC. The solution was passed through an IER column filled with a strongly acidic cation exchange resin, and further passed through an AL column containing 6 g of activated alumina to adsorb and capture Re on the alumina. 20 mL of physiological saline (0.9% NaCl) was passed through the AL column on which Re was adsorbed, and a physiological saline solution containing Re (pH 4.8 - 5.2) was recovered.

[0071] Note that 99 the half-life of Mo is 65.94 hours, 99m the half-life of Tc is 6.01 hours. 99The amount of Mo(500Ci) is 1.04 mg, which is one in 500,000 relative to Mo(500g). 99m The amount of Tc(500Ci) was 0.095 mg, which was one in 5,000,000 relative to Mo(500g). At the μCi test level, 99 The radioactivity of Mo was less than 5×10 4 Bq (Becquerel), and the weight ratio relative to Mo(500g) was less than 6e -15 and 99m The radioactivity of Tc was less than 6×10 4 Bq (Becquerel), and the weight ratio relative to Mo(500g) was less than 6e -16 and. From the results of the TcMM test of the high-range (wide-range) radioactivity test from the μCi level to the 80Ci level and the non-radioactivity test equivalent to 500Ci (Mo 500g or more), the separation coefficient of Mo and Tc by AC (selective adsorption of Tc) was 10e 16 or more.

[0072] The recovery amount of Re was 0.092 - 0.096 mg, and the recovery rate of Re was about 94%. 99m Since it is Re equivalent to Tc(500Ci), it is considered that the same result can be obtained when the metal mesh cylindrical container filled with AC is immersed in the Mo solution to 99m adsorb and collect Tc with AC. This result shows that even when the ratio of the number of atoms of Mo to 99 the daughter nuclide 99m Tc generated by the decay of Mo 99 is 10 16 or more, a small amount of 99m Tc in it can be selectively adsorbed by AC.

[0073] According to the present invention, a high-concentration Mo solution containing radioactive 99 Mo is generated and left standing for about 24 hours to 99 generate 99m Tc from Mo and make them coexist in a state of radioactive equilibrium (the ratio of the radioactivity of the parent nuclide and the daughter nuclide is constantly balanced). Instead of passing the solution through an AC column as in the conventional method, by immersing the AC-filled metal mesh cylindrical container in the stirring and flowing Mo solution, constantly 99mTc can be adsorbed and captured by AC.

[0074] Whether the amount of the high-concentration Mo solution is small, for example, 0.1 L, or large, such as 5 to 20 L, 99 from Mo 99m the elapsed time for Tc to be generated and reach radioactive equilibrium or the desired 99m amount of Tc is generated, at the time when the 99m Tc is selectively adsorbed and collected by AC, so it is particularly effective for the recovery of 99m Tc with a short half-life (6 hours).

[0075] When desorbing the Tc adsorbed and collected by AC in the metal mesh cylindrical container, the Mo ( 99m Mo) that remains non-adsorbed on the AC also 99 Mo) 99m is eluted simultaneously with Tc, but 99m by passing the Tc recovery solution through an alumina column, high-purity 99 Tc can be purified and recovered as a pharmaceutical raw material without contamination by radioactive impurities such as Mo ( 99m Mo).

Example

[0076] The adsorption of Mo and Tc on activated carbon (AC) or aluminum oxide (alumina: AL) is affected by pH conditions. For example, for water-soluble Mo compounds such as Na2MoO4 and (NH4)2MoO4, by changing the pH (acidic to neutral to alkaline), the adsorption or desorption on AC or AL can be controlled. At low pH (for example, acidic around pH 1 to 5), Mo forms a higher-order oxide structure such as MoO 21 6- and has the property of being adsorbed and retained in large amounts on AC, AL, etc. in the state of Mo oxide with a high volume density.

[0077] The method for purifying and recovering medical technetium 99m from low-specific-activity molybdenum 99 is to adsorb a large amount of Mo ( 99 Mo) on AC or AL in the previous stage to make the 99 Tc generated from Mo ( 99mElute Tc and use AL in the subsequent stage 99m LSA for purifying and concentrating Tc 99 Mo / 99m It uses a Tc small generator (TcPG). Also, the TcPG is constructed with a purification and recovery system for medical technetium 99m from low specific activity molybdenum 99.

[0078] Na2Mo( 99 When the Na2Mo( 99 Mo)O4 solution is in a low pH state (about pH 1 - 5), a polymer of molybdenum oxide containing Mo (poly-Mo( 99 Mo)Oxide) is generated in the solution and adsorbed and retained on AC at about 0.2 g (Mo) / g (AC) or more. AC or AL (in the case of AC, about 5 g: adsorbed Mo 1.0 - 1.2 g) adsorbed with Mo( 99 Mo) is filled into a column container and washed with physiological saline (0.9% NaCl solution adjusted to pH with HCl) to 99m make a 99 Mo (molybdenum 99) adsorption column for Tc milking.

[0079] Note that the column container has a structure where granular materials are filled in a cylindrical container or the like and the liquid poured in can be discharged. As a method of adsorbing Mo on AC 99 there are a method of immersing a metal mesh cylindrical container filled with AC or AL in a Mo( 99 Mo) solution, and a method of flowing a Mo( 99 Mo) solution through a column container filled with AC or AL.

[0080] In the subsequent stage of the previous stage Mo( 99 Mo) adsorption column, by using weakly acidic type aluminum oxide (weakly acidic alumina AL) to 99m elute Tc 99m and installing a 99 Tc (technetium 99m) purification column, it becomes an LSA 99m Mo /

[0081] 99mAs for Tc mini generators, there are methods such as using the sol-gel reaction with heavy metals such as zirconium (Zr) and titanium (Ti), using only a large amount of alumina with low Mo adsorption capacity, and using mesoporous alumina (porous weakly acidic alumina) with high Mo adsorption capacity. In contrast, the method for purifying and recovering medical technetium 99m from low-specific-activity molybdenum 99 does not use heterogeneous heavy metals, and uses AL and the light element carbon (C) that have been used in the 99 Mo / 99m Tc mini generators, and has an LSA 99 with a high Mo( 99m Mo) adsorption retention amount and purity and high 99 Mo / 99m Tc elution and recovery property for Tc.

[0082] Even if the specific-activity concentration of Mo( 99 Mo) changes, when making an Mo( 99 Mo) adsorption column with AC or AL adsorbed with Mo, the amount of AC or AL can be changed. In this case, the 99 subsequent Tc purification column once collects and recovers the Tc eluted from the Mo( 99m Mo) adsorption column, and since the concentration of the recovered 99 Tc becomes approximately the same, it is possible to keep the ability of the 99m Tc generator constant even when the Mo( 99m Mo) specific-activity concentration changes or the radioactivity decays within a certain range. 99 Mo) specific-activity concentration changes or the radioactivity decays within a certain range. 99m Tc generator constant even when the Mo(

[0083] Figure 6 is a diagram showing the outline of a low-specific-activity molybdenum 99 / technetium 99m mini generator in the method for purifying and recovering medical technetium 99m from low-specific-activity molybdenum 99 according to the present invention.

[0084] In the front stage, an Mo( 99 Mo) adsorption column with low-specific-activity 99 Mo adsorbed on AC or AL, and in the subsequent stage, an LSA 99m Tc purification column using AL is arranged. 99 Mo / 99mThe basic configuration of the Tc small generator and the flow of the solution will be described.

[0085] First, a low specific activity Mo ( 99 Mo) solution with a low pH (about pH 1 to 5) is passed through a Mo ( 99 Mo) adsorption column. Mo ( 99 Mo) is adsorbed on the 99 Mo adsorption column, and the outflowing Mo ( 99 Mo) solution is removed.

[0086] Next, physiological saline with a low pH (about pH 1 to 5) is passed through to wash the Mo ( 99 Mo) adsorption column. The physiological saline flowing out by washing is removed as waste liquid. By leaving it as it is for about 24 hours, a part of the 99 Mo adsorbed on the Mo ( 99 Mo) adsorption column decays and 99m Tc is generated.

[0087] Next, physiological saline with a low pH (about pH 1 to 5) is passed through the Mo ( 99 Mo) adsorption column. 99 TcO4 99m elutes from the Mo ( - Mo) adsorption column, so it is passed through a 99m Tc purification column. 99m TcO4 99m is captured by the - Tc purification column, and the outflowing waste liquid is removed.

[0088] Finally, physiological saline with a neutral pH is passed through the 99m Tc purification column. The initial outflow liquid is removed, but 99m TcO4 99m elutes from the - Tc purification column, so it is recovered as purified 99m Tc.

[0089] Figure 7 is a diagram showing the process and conditions of the method for purifying and recovering medical technetium 99m from low specific activity molybdenum 99 according to the present invention.

[0090] AC can be either crushed activated carbon or spherical activated carbon made from coconut shells, as long as it has a specific surface area of 1000 m 2 / g or more after activation treatment and contains no eluted impurities. Examples of AL include mesoporous alumina granular products with high Mo adsorption capacity and shaped bodies of nano-sized porous alumina.

[0091] 99 Uranium is not used as the raw material for Mo, and it is low-radioactivity 99 Mo produced from natural isotope Mo. Its specific radioactivity concentration is preferably about 0.5 Ci / g (Mo) or more.

[0092] Note that after the Mo( 99 Mo) adsorption column, 99m the Tc purification column 99m has the function of concentrating Tc. Therefore, even if the specific radioactivity concentration is low (for example, about 0.1 - 0.2 Ci / g (Mo)), by increasing the amount of AC or AL in the Mo( 99 Mo) adsorption column, high-purity 99m Tc with the desired concentration can be recovered.

[0093] The Mo adsorption amount of AC or AL is preferably about 1.0 - 1.2 g (Mo) / 5 - 10 g (AC or AL). The Mo( 99 Mo) adsorption column can be 5 - 10 g for AC and 10 - 12 g for AL. For the Mo( 99 containing 500 mCi of Mo) adsorption column, by using 10 - 25 mL of low-pH saline and milking for 5 - 20 minutes, 500 mCi of 99m Tc can be eluted, and the concentration is controllable.

[0094] 99m When recovering Tc with the Tc purification column 99m it can be obtained with a purity of 95% or more by using 10 - 25 mL of pH-neutral saline. At the use point such as a hospital, high-purity 99mTc can be obtained in a short time (about 5 to 20 minutes), and the generated radioactive waste has a low radioactivity level and a small amount.

[0095] FIG. 8 is a diagram showing a method for producing a molybdenum-99 adsorption column in a method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention.

[0096] Mo( 99 As a method for producing a Mo( 99 Mo) adsorption column, a metal mesh cylindrical container incorporating AC or AL is immersed in a Mo( 99 Mo) solution to adsorb Mo( 99 Mo) on AC or AL by an immersion method, and a Mo( 99 Mo) solution is passed through a column container filled with AC or AL to adsorb Mo( 99 Mo) by a flow method.

[0097] In advance, 99 a low-pH Mo( 99 Mo) solution is stored in a Mo(500 Ci) tank. The tank is provided with a stirring function such as a stirrer.

[0098] In the case of the immersion method, a number of metal mesh cylindrical containers filled with 5 to 20 g of AC or AL in a cylindrical SUS mesh are prepared and collectively put into the flowing Mo( 99 Mo) solution by stirring. Then, the metal mesh cylindrical container is taken out of the tank and washed with low-pH H2O or physiological saline to obtain a Mo( 99 Mo) adsorption column.

[0099] In the case of the flow method, a Mo( 99 Mo) solution is allowed to flow into a column container filled with AC or AL from the tank, and the flowed-out Mo( 99 Mo) solution is refluxed to the tank by a pump. Then, the column container is used as a Mo( 99 Mo) adsorption column as it is.

[0100] Figure 9 is a diagram showing the equipment configuration of a low-specific-activity molybdenum-99 / technetium-99m small generator in the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention.

[0101] Mo( 99 Since strong external radiation (β-rays and γ-rays) is emitted from the Mo( 99 Mo) adsorption column, the Mo( 99m Tc emits only relatively weak γ-rays (141 keV), so 99m the shielding for the Tc purification column etc. can be light.

[0102] LSA 99 Mo / 99m The low-specific-activity molybdenum-99 / technetium-99m small generator is provided with a supply container for the inflow liquid such as physiological saline, a recovery container for the outflow liquid such as the cleaning liquid separated from the flow from the Mo( 99 Mo) adsorption column to the 99m Tc purification column, 99m a recovery container for the 99m Tc purified by removing impurities from the Tc purification column, etc.

[0103] Mo( 99 As the inflow liquid to the Mo( 99 Mo) adsorption column, there are LSA 99 Mo solution (pH 1 - 5), physiological saline for cleaning (low pH), physiological saline for elution (low pH), etc. As the outflow liquid from the Mo( 99 Mo) adsorption column, there are

[0104] 99m As the inflow liquid to the Tc purification column, there is physiological saline (pH neutral), etc. 99m As the outflow liquid from the Tc purification column, there are the waste liquid when 99 Tc is eluted from the Mo( 99m Mo) adsorption column, 99m the initial outflow liquid when 99m Tc is purified from the Tc purification column, etc.

[0105] Figure 10 is a diagram showing the influence of pH on the adsorption property of activated carbon in the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention. Note that 99m As a substitute for Tc, Re (rhenium), which is a group element, is used.

[0106] In the vicinity of pH 1 to 5, up to 1.2 g (Mo) / 5 g (AC) of Mo is adsorbed, and hardly any Re is adsorbed. That is, it can be seen that Mo is strongly adsorbed to AC and Re (Tc) is not adsorbed in the vicinity of pH 1 to 5.

[0107] Figure 11 is a diagram showing the influence of pH on the adsorption property of alumina in the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention. In the case of AL as well as in the case of AC, it can be seen that the adsorption rate and adsorption amount of Mo are large and the adsorption rate and adsorption amount of Re (Tc) are small in the vicinity of pH 1 to 5.

[0108] Figure 12 is a diagram showing the results of a milking test of the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention.

[0109] As shown in Figure 12(a), when the operation of eluting Tc from the Mo ( 99 Mo) adsorption column is repeated once a day for 5 days (5 times), 99m the elution rate of Tc is 90% or more. 99m Tc elution rate has shown results of 90% or more.

[0110] As shown in Figure 12(b), 99m when pH-neutral physiological saline (~30 mL) is passed through the Tc purification column, 99m all of the Tc is eluted from the Tc purification column with 10 mL of physiological saline. 99m Tc has eluted in full volume.

[0111] Figure 13 is a diagram showing the results of gamma-ray measurement of the radiochemical purity of technetium-99m purified and recovered by the method for purifying and recovering medical technetium-99m from low-specific-activity molybdenum-99 according to the present invention. Mo ( 99Mo) adsorption column and elution recovery 99m From the γ-ray spectrum data of the 99m Tc solution, it can be seen that

[0112] According to the present invention 99 The method for producing 98 Mo uses molybdenum with a natural isotope ratio without using enriched uranium as a raw material, and is one of the Mo isotopes naturally contained at 24.1%. 98 Neutron activation of 99 Mo is produced by the

[0113] According to the present invention, it is possible to realize a small generator capable of extracting radioactive technetium 99m as a raw material for radioactive pharmaceuticals and its labeled compound raw materials using radioactive molybdenum 99 with low specific radioactivity at a use point such as a hospital. Under acidic (pH 1 - 5) conditions, by utilizing the property that Mo (molybdenum 99) is adsorbed on AC (activated carbon) or AL (alumina) at about 1 g (Mo) / 5 g (AC or AL), and Tc (technetium 99m) is not adsorbed on AC or AL, a practical LSA 99 Mo / 99m Tc portable generator (TcPG) is obtained.

[0114] For the 98 Mo(n,γ) 99 In the 99 Mo reaction, there is also a drawback that the radioactivity concentration of the generated 99 Mo is extremely low compared to the case where uranium is used as a raw material. In the LSA 99m Tc small generator, heavy metals such as Zr and Ti were used as Mo adsorbents, so practical application has not progressed. However, in the present invention 99 Mo adsorption column and 99m Since the Tc collection and concentration AL column structure does not use heavy metals, it can be approved with a minor pharmaceutical change application.

[0115] Mo( 99 Mo), according to the specific radioactivity concentration of 99If the amount of AC adsorbing Mo is increased or decreased (for example, 5 to 30 g / column), 99 it becomes a tank for storing a certain amount of Mo. 99 Changed from Mo 99m By eluting Tc and concentrating and collecting it in the subsequent AL column, 99m the amount of Tc milking can be controlled. Even if the specific activity concentration of Mo( 99 Mo) increases or decreases within a certain range, the equivalent 99m Tc generating ability of LSA 99 Mo / 99m It becomes a Tc generator.

[0116] Conventional 99 Mo / 99m In the conventional Mo / Tc small generator, HSA (high specific activity of about 10,000 Ci / g(Mo)) generated by the nuclear fission reaction of uranium 99 with a very small amount of Mo adsorbed 99m Tc was eluted from the purification column with physiological saline 99m Tc.

[0117] In the present invention, in front of the Tc purification column provided with AL, LSA (low specific activity of 0.5 Ci / g(Mo) or less) of Mo( 99m Mo) is adsorbed on AC or AL at the 1 g level to 99 store Mo. A Mo( 99 Mo) adsorption column is required, and the reason is the overwhelming low specific activity (a difference of about 10,000 times). 99 Mo) adsorption column and

[0118] The above describes the embodiments of the present invention, but the present invention is not limited thereto. The content of the Mo( 99 Mo) adsorption column and 99m AC and AL, which are the contents of the Tc purification column, are not special, 99m and can be sterilized by high-temperature dry heat or moist heat autoclave according to the radioactive drug standards of the Tc small generator.

Explanation of symbols

[0119] 100: Mo solution tank 110: Stirrer 120: Metal mesh cylindrical container 130: Support tool 140: Hot cell 150: IER column 160: AL column

Claims

1. A method for separating and recovering technetium-99m, a daughter nuclide produced by the decay of molybdenum-99, contained in a high-concentration molybdenum solution containing low-specific-activity molybdenum-99, A molybdenum 99 adsorption column is prepared by filling a metal mesh cylindrical container, which is not a column with a limited flow rate, with activated carbon or alumina, and then immersing the metal mesh cylindrical container in the flowing molybdenum solution, which is maintained at a low pH acidic state and stirred, thereby adsorbing the molybdenum 99 onto the activated carbon or alumina. The technetium 99m generated from the molybdenum 99 is eluted from the molybdenum 99 adsorption column and passed through a technetium 99m purification column packed with weakly acidic alumina to capture the technetium 99m. The technetium-99m is separated and eluted by passing pH-neutral physiological saline through the aforementioned technetium-99m purification column, and then purified and recovered after removing impurities. A method for purifying and recovering medical-grade technetium-99m from low-specific-activity molybdenum-99, characterized by the following features.

2. A method for separating and recovering technetium-99m, a daughter nuclide produced by the decay of molybdenum-99, contained in a high-concentration molybdenum solution containing low-specific-activity molybdenum-99, The process involves making the molybdenum solution acidic with a low pH so that the molybdenum 99 is easily adsorbed by the activated carbon, and then flowing the molybdenum solution through a column container filled with the activated carbon to adsorb and retain the molybdenum 99 on the activated carbon, thereby producing a molybdenum 99 adsorption column in which the molybdenum 99 is stored. The process involves passing a low-pH physiological saline solution, which facilitates the elution of technetium 99m generated from molybdenum 99, through the molybdenum 99 adsorption column, and then passing the low-pH physiological saline solution, from which the technetium 99m has eluted, through a technetium 99m purification column packed with porous, weakly acidic alumina, thereby collecting the technetium 99m that is easily captured by the weakly acidic alumina. The process includes passing pH-neutral physiological saline through the technetium-99m purification column to neutralize the pH inside the technetium-99m purification column, thereby separating and eluting the technetium-99m, and purifying and recovering the technetium-99m from which impurities have been removed. A method for purifying and recovering medical-grade technetium-99m from low-specific-activity molybdenum-99, characterized by the following features.

3. The molybdenum solution contains the radioactive nuclide molybdenum 99, which is produced by the neutron capture (n,γ) reaction of the natural isotope molybdenum. A method for purifying and recovering medical-grade technetium-99m from low specific radioactivity molybdenum-99 according to claim 1 or 2.

4. The amount of activated carbon or alumina used to adsorb the molybdenum 99 is increased or decreased according to the specific radioactivity concentration of the molybdenum 99, thereby changing the concentration of technetium 99m separated and eluted from the molybdenum 99. A method for purifying and recovering medical-grade technetium-99m from low specific radioactivity molybdenum-99 according to claim 1 or 2.

5. A means for producing a high-concentration molybdenum solution containing low specific radioactivity molybdenum 99, which is produced by the neutron capture (n,γ) reaction of the natural isotope molybdenum, A means for producing a molybdenum 99 adsorption column in which the molybdenum 99 is stored by making the molybdenum solution acidic to a low pH so that the molybdenum 99 is easily adsorbed by activated carbon, and by flowing the molybdenum solution through a column container filled with activated carbon, thereby adsorbing and retaining the molybdenum 99 on the activated carbon, A means for producing the daughter nuclide technetium-99m by the decay of molybdenum-99, A means for collecting technetium 99m that is easily captured by the weakly acidic alumina, by passing a low-pH physiological saline solution, which facilitates the elution of technetium 99m generated from the molybdenum 99, through the molybdenum 99 adsorption column, and then passing the low-pH physiological saline solution, from which the technetium 99m has eluted, through a technetium 99m purification column packed with porous weakly acidic alumina, The system includes a means for passing pH-neutral physiological saline through the technetium-99m purification column to neutralize the pH inside the technetium-99m purification column, thereby separating and eluting the technetium-99m, and purifying and recovering the technetium-99m from which impurities have been removed. A system for purifying and recovering medical-grade technetium-99m from low-specific-activity molybdenum-99, characterized by its features.

6. In a metal mesh cylindrical container that is not a column with a limited flow rate, activated carbon or alumina is packed inside, and the container is immersed in the molybdenum solution, which is flowing by stirring after being brought to a low pH acidic state, thereby adsorbing the molybdenum 99 onto the activated carbon or alumina. A molybdenum 99 adsorption column characterized by the following features.

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