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

Abstract

The present invention extracts, at a use point such as a hospital: a radiopharmaceutical using radioactive molybdenum-99 having low specific activity as a raw material; and radioactive technetium-99m, which serves as a labeling compound raw material for the radiopharmaceutical.　Activated carbon or alumina is charged into a metal net-like cylindrical container which is not a column in which flow rate is limited. The metal net-like cylindrical container is immersed in a molybdenum solution brought to a low-pH acidic state and kept flowing by stirring, thereby preparing a molybdenum-99-adsorbed column in which the molybdenum-99 is adsorbed on the activated carbon or the alumina. The technetium-99m generated from the molybdenum-99 is eluted out from the molybdenum-99-adsorbed column and is then passed through a technetium-99m purification column filled with aluminum oxide, thereby capturing the technetium-99m. Physiological saline having a neutral pH is passed through the technetium-99m purification column, thereby separating and eluting out the technetium-99m, which is purified and recovered after impurities are removed therefrom.

Description

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

[0001] The present invention is a method for producing radioactive molybdenum-99 ( ９９ Radiopharmaceuticals made from radioactive technetium 99m (Mo) and radioactive technetium 99m (Mo) as a raw material for their labeled compounds ９９ｍ Tc) relates to a process and system for extracting the same at use points such as hospitals.

[0002] Technetium (Tc) is a transition metal with atomic number 43, located in the 7th group and 5th period. Among the isotopes of Tc, ９９ｍ Technetium 99m (Tc) emits only gamma rays with a short half-life (6 hours) suitable for diagnostic imaging and a low energy (140 keV) suitable for external measurement. ９９ A generator that utilizes radioactive equilibrium with Mo (molybdenum 99) ９９ Mo / ９９ｍ It is generated by a Tc generator and is widely used in nuclear medicine imaging diagnosis. ９９ｍ Tc has a short half-life, so it is usually ９９ Mo (half-life 66 hours) was obtained, ９９ From Mo ９９ｍ It is used in the method for obtaining Tc.

[0003] ９９ Until now, the only method of obtaining Mo has been fissile uranium ( ２３５ It is produced using the nuclear fission method of neutron irradiation of uranium (U), and has a very high specific radioactivity (the strength of radioactivity per unit mass of a substance containing a radioactive isotope). ９９ The fission method, which produces Mo and separates it from the fission products produced at the same time, has been used as a practical technology around the world. ９９ Because Mo has a high specific radioactivity, aluminum oxide (alumina), which is generally used for medical purposes, is used as an adsorbent to adsorb Mo ( ９９ Mo) and adsorbed on an alumina column. ９９ Mo) ９９ Mo daughter nuclides​９９ｍ By eluting (milking) Tc with saline ９９ｍ The method for obtaining Tc is used as a practical manufacturing technique.

[0004] on the other hand, ９９ Uranium is not used as a raw material for obtaining Mo, but rather a molybdenum compound is used as the raw material, and Mo is included 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 n undergoes a nuclear reaction and emits γ rays when it changes into a radioactive substance), ９９ There is a method to generate Mo, and it is generated by this (n, γ) method. ９９ Compared with the Fission method, Mo ９９ The specific activity of Mo is extremely low, about 1 / 10,000 (hereinafter, low specific activity will be referred to as LSA). Therefore, in order to put the (n, γ) method into practical use, it is necessary to consider the trace amounts of non-radioactive Mo contained in the large amount of non-radioactive Mo. ９９ A trace amount of daughter nuclide produced from Mo ９９ｍ It is necessary to separate, purify and recover Tc.

[0005] To date, the activated carbon method, the sol-gel method, the MEK method, and the sublimation method have been investigated and put into practical use as (n, γ) methods. ９９ｍ A large amount of Tc-labeled compounds are produced at pharmaceutical manufacturers' plants. ９９ A large amount of Mo ９９ｍ On the other hand, at use points such as hospitals, the amount of Tc needed for a single patient or several patients is calculated. ９９ｍ Tc is often extracted and recovered for use.

[0006] High specific radioactivity made from uranium ９９ Low specific activity LSA using Mo compounds as raw materials instead of Mo ９９ Use Mo ９９ｍ Although many attempts have been made to develop small Tc generators (TcPG: Technetium-99m portable generators), they have not yet been put to practical use for the following reasons: The present inventors have developed and proposed a PZC (polyzirconium compound) method, which is a type of sol-gel method.

[0007] Patent Document 1 describes radioactive molybdenum, which is the parent nuclide of technetium. ９９ Mo is produced by irradiating natural isotopes of Mo with neutrons in a nuclear reactor. ９８ It is produced by the Mo(n,γ) reaction, ９９ By passing a Mo solution containing Mo through an activated carbon (AC) column, ９９ It is a daughter nuclide of Mo ９９ｍ The Tc was selectively adsorbed onto AC and collected, and the non-adsorbed Mo( ９９ The sintered body (including Mo) is washed away with water, and then adsorbed onto AC using an alkaline solution (e.g., caustic soda NaOH). ９９ｍ Tc is eluted from the AC, and ９９ｍ Mo contained in the Tc recovery solution, ９９ Mo, radioactive impurities, and other impurities are removed by passing the liquid through an AL column packed with aluminum oxide (alumina) placed after the AC column. ９９ｍ A method and apparatus for purifying Tc recovery fluid is described.

[0008] In Patent Document 2, similar to Patent Document 1, a method is described in which natural isotope Mo is used as a raw material and neutrons are irradiated in a nuclear reactor. ９８ Produced by the Mo(n,γ) reaction ９９ Mo to its daughter nuclide ９９ｍ Tc was purified using spherical activated carbon (BAC). ９９ｍ a method for recovering Tc; ９９ The method of passing the Mo solution containing Mo through the AC column by either a pressurized flow in which the solution is pushed into the AC column by a pump or a reduced pressure flow in which the solution is sucked in by a pump was compared. After that, the non-adsorbable Mo ( ９９ After washing away the adsorbed carbon black (including Mo) with water, an alkaline solution (e.g., caustic soda NaOH) was used to remove the adsorbed carbon black. ９９ｍ As a method for eluting Tc from AC, we investigated a method of accelerating elution by heating to about 80°C. ９９ｍ Mo contained in the Tc recovery solution, ９９ Mo, radioactive impurities, and other impurities are removed using a column packed with Al placed after the AC column. ９９ｍA method and apparatus for purifying Tc recovery fluid is described.

[0009] In Patent Document 3, similar to Patent Documents 1 and 2, a method for producing uranium dioxide by irradiating natural isotopes of Mo as a raw material with neutrons in a nuclear reactor is described. ９８ Produced by the Mo(n,γ) reaction ９９ Mo to its daughter nuclide ９９ｍ The main methods for recovering Tc using AC are: ９９ It was installed inside a double-walled cell to shield radiation such as gamma rays emitted from Mo and prevent leakage of radioactive materials. ９９ The Mo solution tank containing Mo is piped to an external cell equipped with an AC column with low radiation shielding capability, and the Mo solution is piped to the AC column installed in the external cell and then circulated back to the internal Mo solution tank. ９９ｍ The structure is such that it selectively adsorbs and collects Tc to prevent radiation leakage to the outside, and then the activated carbon non-adsorbable Mo( ９９ After washing away the adsorbed carbon black (including Mo) with water, an alkaline solution (e.g., caustic soda NaOH) was used to remove the adsorbed carbon black. ９９ｍ Tc is eluted from the AC and finally ９９ｍ Mo contained in the Tc recovery solution, ９９ Mo, radioactive impurities, and other impurities are removed by passing the solution through a column filled with AL placed after the AC column. ９９ｍ A method and apparatus for purifying Tc recovery fluid is described.

[0010] The PZC method described in Patent Documents 4 to 6 uses an inorganic polymer compound (polyzirconium compound) composed of zirconium (Zr), oxygen (O) and chlorine (Cl) to form a zirconium-O-Mo bond. ９９ Mo is bound to the PZC at a ratio of 200 to 250 mg (Mo) / g (PZC) per unit weight of PZC. ９９ Mo- ９９ｍ The basic characteristics of the Tc generator are ９９ｍ It also has excellent Tc milking properties. However, because PZC contains the heavy metal zirconium, it was deemed difficult to apply for changes to the radiopharmaceutical standards, and practical application did not progress.

[0011] Similarly, in the case of Patent Document 7, a molybdenum compound containing molybdenum-99 selected from the group consisting of zirconium molybdate, titanium molybdate, cerium molybdate, iron molybdate, tin molybdate, and mixtures thereof is used as a matrix that enables the elution of technetium-99m, and all of these compounds contain heavy metals such as Zr (zirconium), Ti (titanium), Ce (cerium), Fe (iron), and Sn (tin), and therefore it was deemed difficult to apply for a change in the radiopharmaceutical standards, and practical application of these compounds did not progress.

[0012] Patent Document 8 describes LSA ９９ When alcohol such as ethanol, propanol, or isopropyl alcohol is used as a precipitant in the Mo solution, Mo ( ９９ 99% of the nuclides (Mo) precipitate and are easy to recover. ９９ｍ However, this method requires a short time at the point of use, such as a hospital. ９９ｍ LSA for diagnosis by milking (elution and recovery) Tc ９９ Mo / ９９ｍ It cannot be used as a small Tc generator.

[0013] Japanese Patent No. 5427483 Japanese Patent No. 5916082 Japanese Patent No. 6355462 Japanese Patent No. 2857349 Japanese Patent No. 2862837 Japanese Patent No. 4386631 U.S. Patent No. 04280053 U.S. Patent No. 12040102

[0014] The prior art described in Patent Documents 1 to 3 is ９９ Generated in a Mo solution containing Mo ９９ｍ To recover Tc, a metal cylindrical container (column) was placed inside, to which the inlet and outlet of the Mo solution were connected. ９９ｍ The column is packed with AC capable of selectively adsorbing Tc, and a Mo solution is passed through the column.

[0015] In the conventional method, the solution is passed through an AC column to extract the molybdenum contained in the Mo solution. ９９ｍ To completely adsorb and capture Tc, Mo( ９９ Mo) solution ( ９９It is necessary to limit the flow rate when passing a Mo solution (containing Mo) through a flow-through AC column. Specifically, for low specific activity Mo solutions, ９９ Because the Mo concentration is low, the desired amount ９９ｍ To recover Tc, a large amount of Mo ( ９９ Mo) solution must be passed through the AC column. For example, when the flow rate per unit time for passing the solution through an AC column packed with 5 g of AC is 50 to 100 mL / min at maximum, 2.0 L of Mo( ９９ It takes 20 to 40 minutes or more to pass the Mo solution through the membrane, and the membrane has a short half-life. ９９ｍ The task of recovering Tc in a short time and using it for diagnostic purposes lies in work efficiency.

[0016] However, Mo ( ９９ When the amount of Mo) solution is, for example, 5 to 20 L, ９９ｍ It takes 2 to 5 hours or more to pass the solution through the AC column to adsorb and collect Tc, which reduces the work efficiency and reduces the recovery time of the short half-life of the recovered Tc. ９９ｍ Tc is altered ９９ｇ There is a risk that it will become Tc and become unusable as a pharmaceutical raw material. ９９ｇ Tc (Technetium 99 ground state) is ９９ｍ It is a radioactive isotope of Tc produced from Tc with a half-life of 211,100 years, and is used as a pharmaceutical raw material. ９９ｍ It is produced in proportion to the time that has passed since the extraction and separation of Tc. If there is too much, it will become a pharmaceutical raw material. ９９ｍ It becomes an impurity of Tc.

[0017] Radioactive molybdenum 99 ( ９９ Mo) into the high concentration Mo solution ９９ It is produced by the decay of Mo and is contained in ９９ Technetium 99m, a daughter nuclide of Mo ( ９９ｍ In order to recover Tc, the ratio of the number of atoms is 10 １６ The above Mo ( ９９ Even if Mo) is present, only a small amount of ９９ｍ It is sufficient to use AC that can selectively adsorb and recover Tc.

[0018] Formed in highly concentrated Mo solutions９９ Mo daughter nuclides ９９ｍ As a method for selectively separating and recovering Tc, a cylindrical metal mesh container containing AC is immersed in a Mo solution, and the surrounding Mo solution is stirred and flowed to separate Tc in the Mo solution. ９９ｍ If the method is to adsorb and collect Tc, there is no need to pass the solution through an AC column, which requires flow rate restriction. ９９ｍ If Tc is adsorbed and collected by AC immersed in a Mo solution, it is not necessary to pass the solution through the AC column for a long time.

[0019] In addition, it can be used at hospitals and other use points in a short time. ９９ｍ In order to enable diagnosis by milking (elution and recovery) Tc, highly non-radioactive radioactive materials manufactured from enriched uranium have been used. ９９ Mo was supported on alumina ９９ｍ Tc generators have been used. However, ９９ｍ It is the parent nuclide of Tc ９９ To produce Mo, enriched uranium is used as a raw material, which raises issues regarding nuclear safety, ９９ There is also the problem of high-level fission waste generated and accumulated during Mo production. ９９ Mo production is dependent on irradiation reactors located in Europe, South Africa, Australia, etc., and these reactors are aging, causing frequent operational and transportation problems. ９９ Mo production and supply have been frequently disrupted ９９ｍ Tc has problems such as interfering with medical diagnosis.

[0020] Mo raw material ９８ Mo(n, γ) ９９ In the Mo reaction, ９９ The radioactivity concentration of Mo is 1 / 10,000 of that of uranium, so it is used as low specific radioactivity LSA at points of use such as hospitals. ９９ Mo / ９９ｍ The small Tc generator has not yet been put to practical use. ９９ Mo / ９９ｍIn the case of small Tc generators, the use of heavy metals such as Zr and Ti as Mo adsorbents has hindered practical application.

[0021] Molybdate ions in aqueous Mo solution, e.g., Na ２ MoO ４ Ya (NH ４ ) ２ MoO ４ Water-soluble Mo compounds such as these have low adsorption to activated carbon at neutral to alkaline pH, while Tc is adsorbed to activated carbon. On the other hand, at low pH (e.g., acidic pH around 1 to 5), Mo is adsorbed to Mo. ６ O ２１ ６－ This creates a high-order oxide structure (a kind of polymeric form) and has the property of being adsorbed and held in large quantities on activated carbon or alumina in the form of Mo oxide with high volume density.

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

[0023] Another object of the present invention is to provide a small generator that can extract radiopharmaceuticals made from low-specific activity radioactive molybdenum-99 and radioactive technetium-99m, which is used as a raw material for labeling compounds thereof, at points of use such as hospitals.

[0024] In order to solve the above problems, the method of the present invention for recovering technetium-99m from low specific activity molybdenum-99 is a method for recovering technetium-99m, a daughter nuclide produced by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing molybdenum-99 with low specific activity, by separating and recovering the technetium-99m with activated carbon, the daughter nuclide being produced by the decay of molybdenum-99. The activated carbon is filled in a cylindrical metal mesh container that is not a column with a limited flow rate, and is immersed in the molybdenum solution that is flowing due to stirring, thereby selectively adsorbing trace amounts of technetium-99m in the molybdenum solution.

[0025] In the method for recovering technetium-99m from low specific activity molybdenum-99, the molybdenum solution contains the radionuclide molybdenum-99 produced by the neutron capture (n, γ) reaction of the natural isotope of molybdenum.

[0026] The present invention also provides a method for producing a physiological saline solution containing technetium-99m, which comprises washing with water the molybdenum remaining in the pores of activated carbon to which technetium-99m recovered by the method for recovering technetium-99m from low specific activity molybdenum-99 has been adsorbed, eluting the solution containing technetium-99m from the activated carbon with an alkaline solution, passing the solution through an IER column packed with a strongly acidic cation exchange resin to remove alkaline components, and further passing the solution through an AL column packed with alumina to capture the technetium-99m. Technetium-99m is then eluted from the AL column using physiological saline, thereby purifying the solution into a physiological saline solution containing technetium-99m from which impurities have been removed.

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

[0028] Furthermore, the system for recovering technetium-99m from natural molybdenum of the present invention comprises: means for producing a highly concentrated molybdenum solution containing molybdenum-99 with low specific activity produced by the neutron capture (n, γ) reaction of the natural isotope of molybdenum; means for producing the daughter nuclide technetium-99m in the molybdenum solution by the decay of molybdenum-99; means for filling a cylindrical metal mesh vessel, which is not a column with a limited flow rate, with activated carbon and immersing the activated carbon in the molybdenum solution that is being stirred and flowing; and The method comprises: a means for washing residual molybdenum-99 from the activated carbon on which technetium-99m has been adsorbed; a means for eluting technetium-99m from the washed activated carbon with an alkaline solution, passing the eluate through a strongly acidic cation exchange resin column to remove the alkaline components, and passing the resulting solution through an alumina column to capture technetium-99m; and a means for eluting technetium-99m from the alumina column with physiological saline and recovering purified technetium-99m.

[0029] In order to solve the other problem described above, the present invention provides a method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99. This method separates and recovers the daughter nuclide technetium-99m produced by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low specific activity molybdenum-99. The method comprises filling activated carbon or alumina into a metal mesh cylindrical container, which is not a column with a limited flow rate, and immersing the metal mesh cylindrical container in the molybdenum solution, which is in a low pH acidic state and is being stirred to flow. a molybdenum-99 adsorption column in which the molybdenum-99 is adsorbed onto the activated carbon or alumina by this process; the technetium-99m produced 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; and the technetium-99m is separated and eluted by passing a pH-neutral physiological saline solution through the technetium-99m purification column, whereupon the technetium-99m is purified and recovered after impurities have been removed.

[0030] Furthermore, the method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 of the present invention is a method for separating and recovering the daughter nuclide technetium-99m produced by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low specific activity molybdenum-99, characterized in that the molybdenum solution, which has been made into an acidic state with a low pH, is passed through a column container packed with activated carbon or alumina to prepare a molybdenum-99 adsorption column in which the molybdenum-99 is adsorbed onto the activated carbon or alumina, the technetium-99m produced from the molybdenum-99 is eluted from the molybdenum-99 adsorption column, and the technetium-99m is captured by passing the eluate through a technetium-99m purification column packed with weakly acidic alumina, and the technetium-99m is separated and eluted by passing a neutral pH physiological saline solution through the technetium-99m purification column, and the technetium-99m is purified and recovered after impurities are removed.

[0031] Furthermore, in the method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99, the molybdenum solution contains the radionuclide molybdenum-99 produced by the neutron capture (n, γ) reaction of the natural isotope of molybdenum.

[0032] Furthermore, in the method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99, the amount of activated carbon or alumina that adsorbs the molybdenum-99 is increased or decreased depending on the specific activity concentration of the molybdenum-99, thereby changing the concentration of the technetium-99m that is separated and eluted from the molybdenum-99.

[0033] Furthermore, the system for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 of the present invention is characterized by comprising: means for producing a high-concentration molybdenum solution containing low specific activity molybdenum-99 produced by the neutron capture (n,γ) reaction of the natural isotope of molybdenum; means for preparing a molybdenum-99 adsorption column in which the molybdenum-99 is adsorbed onto activated carbon or alumina by making the molybdenum solution acidic at a low pH; means for producing a daughter nuclide, technetium-99m, by the decay of the molybdenum-99; means for capturing the technetium-99m by eluting the technetium-99m from the molybdenum-99 adsorption column and passing the eluate through a technetium-99m purification column packed with weakly acidic alumina; and means for separating and eluting the technetium-99m by passing a neutral pH physiological saline solution through the technetium-99m purification column, removing impurities, and recovering the technetium-99m.

[0034] Furthermore, the molybdenum-99 adsorption column of the present invention is characterized in that activated carbon or alumina is packed into a metal mesh cylindrical container that is not a column in which the flow rate is limited, and the metal mesh cylindrical container is immersed in the molybdenum solution that has been made acidic at a low pH and is being stirred to flow, thereby allowing the molybdenum-99 to be adsorbed onto the activated carbon or alumina.

[0035] According to the present invention, radioactive ９９ A high-concentration Mo solution containing Mo is produced and left for about 24 hours. ９９ From Mo ９９ｍ Tc is generated and mixed in a state of radioactive equilibrium (the ratio of the radioactivity of the parent nuclide to the daughter nuclide is constantly balanced), and instead of passing the solution through an AC column as in the past, an AC-filled metal mesh cylindrical container is immersed in a stirred and flowing Mo solution, so that the ９９ｍ Tc can be captured by adsorption onto AC.

[0036] Whether the amount of high-concentration Mo solution is as small as 0.1 L or as large 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 At the time when the amount of Tc is generated, the target amount９９ｍ Since Tc is selectively adsorbed and collected on AC, it is particularly effective for Tc with a short half-life (6 hours). ９９ｍ It is effective in recovering Tc.

[0037] The adsorption and collection of AC in a cylindrical metal mesh container ９９ｍ When desorbing Tc, the remaining Mo( ９９ Mo) also ９９ｍ It leaches out at the same time as Tc, ９９ｍ By passing the Tc recovery solution through an alumina column, Mo( ９９ It is free from radioactive impurities such as ZnO, and is of high purity suitable for pharmaceutical raw materials. ９９ｍ Tc can be purified and recovered.

[0038] Also, the present invention ９９ The Mo production method does not use enriched uranium as a raw material, but uses molybdenum with a natural isotope ratio, which is one of the Mo isotopes that occurs naturally at 24.1%. ９８ Neutron activation of Mo ９８ By the Mo(n,γ) reaction ９９ It is what makes Mo.

[0039] According to the present invention, it is possible to realize a small generator capable of extracting radiopharmaceuticals made from low specific activity radioactive molybdenum-99 and radioactive technetium-99m as a raw material for their labeled compounds at points of use such as hospitals. Under acidic conditions (pH 1-5), Mo (molybdenum-99) adsorbs to AC (activated carbon) or AL (alumina) at a rate of approximately 1 g (Mo) / 5 g (AC or AL), and Tc (technetium-99m) elutes without adsorbing to the Mo (molybdenum-99) layered and adsorbed on AC or AL. This allows for practical LSA. ９９ Mo / ９９ｍ This becomes the Tc Portable Generator (TcPG).

[0040] Mo raw material ９８ Mo(n, γ) ９９ In the Mo reaction, ９９ The radioactivity concentration of Mo is extremely low compared to when uranium is used as a raw material, which is a drawback. ９９ Mo / ９９ｍIn the case of small Tc generators, heavy metals such as Zr and Ti were used as Mo adsorbents, which prevented practical application. ９９ Mo adsorption column and ９９ｍ Since the TC collection and concentration AL column configuration does not use heavy metals, it can be approved with a minor drug change application.

[0041] 1 is a diagram showing an outline of a method for extracting technetium-99m from low specific activity molybdenum-99 according to the present invention, a method for producing a physiological saline solution containing technetium-99m using that method, and a system for recovering technetium-99m from natural molybdenum.

[0023] FIG. 1 is a diagram showing a conventional method for passing a molybdenum solution through an activated carbon column.

[0024] FIG. 1 is a diagram showing a method for extracting technetium-99m from low specific activity molybdenum-99 according to the present invention, a method for producing a physiological saline solution containing technetium-99m using that method, and the configuration of a system for recovering technetium-99m from natural molybdenum.

[0025] FIG. 1 is a diagram comparing the process of the present invention for extracting technetium-99m from low specific activity molybdenum-99 with that of a conventional method.

[0026] FIG. 1 is a diagram showing process conditions for short-time production of a method for producing a physiological saline solution containing technetium-99m according to the present invention.

[0027] FIG. 1 is a diagram showing an outline of a small low specific activity molybdenum-99 / technetium-99m generator in a method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention.

[0023] Figure 1 is a diagram showing the process and conditions for the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. Figure 2 is a diagram showing a method for preparing a molybdenum-99 adsorption column in the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. Figure 3 is a diagram showing the equipment configuration of a low specific activity molybdenum-99 / technetium-99m small generator in the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. Figure 4 is a diagram showing the effect of pH on the adsorption of activated carbon in the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. Figure 5 is a diagram showing the effect of pH on the adsorption of alumina in the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. Figure 6 is a diagram showing the results of a milking test for the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. FIG. 1 is a diagram showing the results of gamma ray measurement to examine the radiochemical purity of technetium-99m purified and recovered by the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention.

[0042] ９９ Mo solution containing Mo was passed through the AC column.​９９ｍ Instead of recovering Tc, a cylindrical metal (e.g., stainless steel) mesh container filled with AC is placed in the ９９ The AC container is always immersed in the Mo solution tank, and the Mo solution in which the AC container is immersed is stirred and flowed, so that the AC is always ９９ｍ Tc is made adsorbable.

[0043] At a predetermined or arbitrary timing, the AC container is pulled out from the Mo solution, and the non-adsorbed AC remaining in the AC pores is detected. ９９ After removing Mo by washing with water, ９９ｍ AC was captured by treating the AC with Tc adsorbed in an alkaline solution. ９９ｍ Tc is eluted and the solution is purified with a strong acid cation exchange resin (IER) and alumina (AL) to obtain a highly purified ９９ｍ Tc is recovered.

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

[0045] 1 and 3 show a method for extracting technetium-99m from low specific activity molybdenum-99, a method for producing a saline solution containing technetium-99m using the method, and a system for recovering technetium-99m from natural molybdenum. ９９ Instead of passing the Mo solution containing Mo through an AC column, the Mo solution was passed through a metal mesh cylindrical container filled with AC. ９９ｍ Tc is adsorbed and collected, ９９ｍ Tc is purified and recovered.

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

[0047] The method for extracting technetium-99m from low specific activity molybdenum-99 involves separating and recovering the daughter nuclide technetium-99m produced by the decay of molybdenum-99 contained in a high-concentration molybdenum solution containing molybdenum-99 with low specific activity using activated carbon.

[0048] The activated carbon is packed in a cylindrical metal mesh container, which is not a column in which the flow rate is restricted, and is immersed in a molybdenum solution that is flowing by stirring, and the ratio of the number of molybdenum atoms is 10 １６ Even if more than 99m of technetium is present, the molybdenum solution selectively adsorbs trace amounts of technetium-99m. The molybdenum solution also contains the radioactive nuclide molybdenum-99, which is produced by the neutron capture (n, γ) reaction of the natural isotope molybdenum.

[0049] The method for producing a physiological saline solution containing technetium-99m involves washing with water the molybdenum remaining in the pores of activated carbon to which technetium-99m recovered by a method for recovering technetium-99m from low specific activity molybdenum-99 has been adsorbed, eluting the solution containing technetium-99m from the activated carbon with an alkaline solution, passing the solution through an IER column packed with a strongly acidic cation exchange resin to remove the alkaline components, passing the solution through an AL column packed with alumina to capture the technetium-99m, and eluting the technetium-99m from the alumina column with physiological saline, thereby purifying the solution into a physiological saline solution containing technetium-99m from which impurities have been removed.

[0050] The system for recovering technetium-99m from natural molybdenum includes: means for producing a highly concentrated molybdenum solution containing molybdenum-99 of low specific activity produced by the neutron capture (n,γ) reaction of the natural isotope of molybdenum; means for producing the daughter nuclide technetium-99m in the molybdenum solution by the decay of molybdenum-99; means for filling a cylindrical metal mesh container that is not a column with a limited flow rate with activated carbon and immersing the activated carbon in a molybdenum solution that is being stirred and flowing; means for washing the remaining molybdenum-99 from the activated carbon on which technetium-99m has been adsorbed; means for eluting the technetium-99m from the washed activated carbon with an alkaline solution, passing the resulting solution through a strong acidic cation exchange resin column to remove the alkaline components, and passing the resulting solution through an alumina column to capture the technetium-99m; and means for eluting the technetium-99m from the alumina column with physiological saline and recovering purified technetium-99m.

[0051] As shown in FIG. 1, a tank 100 storing the Mo solution is ９９ Because Mo has a high radiation dose, it is installed in a radiation-shielded hot cell. The Mo solution tank 100 is equipped with a stirrer 110 for stirring the solution, and also with a support 130 for holding a metal mesh cylindrical container 120 containing AC in the solution. Multiple tanks 100 may be installed in the hot cell.

[0052] Radiopharmaceutical raw materials ９９ｍ To produce Tc, a radionuclide ９９ As a Mo solution containing Mo, Na ２ ９９ MoO ４ The solution is supplied to the tank 100. The natural isotope MoO ３ When neutrons are irradiated to ９９ Mo is produced. ９９ MoO containing Mo ３ When dissolved in an alkaline (NaOH) solution, a neutral pH Na ２ ９９ MoO ４ It becomes a solution.

[0053] radioactive ９９The Mo solution containing Mo is, for example, 500 g of Mo (MoO ３ It is a high concentration Mo solution containing 750g of Mo. ９９ｍ To obtain Tc, a highly concentrated Mo solution containing 500 g of Mo in 2 L is required, but 50 g of Mo (MoO ３ A high concentration Mo solution containing 75 g of Mo (MoO ３ A high-concentration, large amount of Mo solution containing 7.5 kg of Mo may also be used.

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

[0055] ９９ Generated from Mo ９９ｍ Since Tc reaches a state of radiation equilibrium in about 24 hours, the metal mesh cylindrical container 120 may be pulled out of the Mo solution after waiting for this time to elapse, or may be pulled out at any time before reaching radiation equilibrium. ９９ｍ Tc can be adsorbed by AC.

[0056] As shown in Figure 2, the conventional TcMM (Technetium 99m Master Milker) ９９ｍ In this method, the entire amount of Mo solution is passed through an AC column to adsorb Tc onto AC. The AC column is a cylindrical container filled with AC, and the liquid comes into contact with the AC as it passes through the cylinder from the inlet to the outlet. In this method, the flow rate of the Mo solution passing through the AC column is limited, which limits the AC column's ability to process the Mo solution, resulting in a short half-life (lifespan). ９９ｍ There are problems with the technology for recovering Tc.

[0057] As shown in Figure 3, from the low specific activity Mo solution​​９９ｍ The system for highly concentrating, purifying and recovering Tc is installed in a hot cell 140 isolated by a thick shielding wall to shield it from high radiation. ９９ MoO ３ Dissolve in alkali ９９ MoO ３ The solution is prepared in advance in a plurality of storage tanks 100 each having a capacity of 1 to 20 L provided in the hot cell 140. ９９ MoO ３ Supply the solution, ９９ A highly concentrated Mo solution with a Mo radioactivity of 500 Ci is stored.

[0058] The metal mesh cylindrical container 120 containing the AC is placed in the tank 100 using a hook, a carrier, etc., and is supported by a support 130. ９９ It is kept in a Mo solution containing Mo. ９９ The collapse of Mo ９９ｍ It changes to Tc, ９９ｍ The result is a Mo solution containing Tc.

[0059] After the metal mesh cylindrical container 120 is immersed in the Mo solution, the Mo solution is stirred with the stirrer 110 so that the Mo solution can be efficiently brought into contact with the AC. ９９ｍ The metal mesh cylindrical container 120 is lifted out of the tank 100. ９９ｍ The AC with adsorbed Tc is collected. Then, the AC is placed in a column and washed with water to remove the remaining non-adsorbed Tc. ９９ Mo and the like are removed by washing.

[0060] An alkaline (NaOH) solution is supplied to the AC-containing column while adjusting the flow rate and temperature. By treating with the alkaline solution, the AC is converted into the alkaline solution. ９９ｍ Tc was eluted and excreted ９９ｍ The alkaline solution containing Tc is passed through the IER column 150. The alkaline component is captured by the strongly acidic cation exchange resin in the IER column 150 and discharged. ９９ｍ A solution containing Tc is passed through the AL column 160 .

[0061] Alumina with AL column 160 ９９ｍThen, by passing physiological saline with a NaCl concentration of about 0.9% through the AL column 160, Tc is captured and the impurities are discharged. ９９ｍ Tc elutes. ９９ｍ TcO ４ It becomes a solution and is excreted with saline, so it is highly purified and ９９ｍ By recovering it as a physiological saline solution containing Tc, it can be used as a raw material for radiopharmaceuticals and labeled compounds.

[0062] High purity from high concentration Mo solution ９９ｍ The waste and waste liquid generated in the process of purifying and recovering Tc can be solidified after the radioactivity attached to them has naturally decayed to a low level. A space for storing and accommodating various radioactive and non-radioactive wastes generated in the process may be provided in the hot cell 140 or the like.

[0063] The container for storing the AC (metal mesh cylindrical container 120, AC storage column for washing the AC with water), the IER column 150, and the AL column 160 are preferably made of materials and have contents (AC, IER, AL) that can be sterilized in an autoclave (121°C, 2 atmospheres).

[0064] As shown in Figure 4, the conventional method and the process of the present invention are compared. In the conventional method, the solution is passed through an AC column to extract the molybdenum contained in the Mo solution. ９９ｍ This is a flow-type TcMM that adsorbs and collects Tc. Instead of passing a Mo solution through an AC column, the present invention immerses a cylindrical metal mesh container 120 containing an AC in a flowing high-concentration Mo solution, thereby adsorbing and collecting Tc. ９９ｍ This is an improved batch-type TcMM in which Tc is adsorbed onto AC.

[0065] In the conventional method, the Mo solution is passed through an AC column to extract the Mo contained in the Mo solution. ９９ｍ To completely adsorb and collect Tc, it was necessary to provide a flow rate restriction in the AC column to allow the Mo solution to flow. Specifically, for low specific activity Mo solution, ９９ Because the concentration of Mo is low, the desired amount ９９ｍTo recover Tc, it is necessary to pass a large amount of Mo solution through the AC column. For example, if the flow rate per unit time for passing the solution through the AC column is set to a maximum of 50 to 100 mL / min, it takes 20 to 40 minutes or more to pass 2.0 L of Mo solution through the AC column, which has a short half-life. ９９ｍ The work efficiency is not good for recovering Tc in a short time and using it for diagnosis.

[0066] Moreover, in the case of a low-concentration Mo solution, ９９ｍ To become Tc, ９９ｍ When Tc is adsorbed and collected on an AC column, a larger amount of Mo solution is passed through the AC column. For example, when the amount of Mo solution is 5 to 20 L, it takes 2 to 5 hours or more to pass the solution through the AC column, and the collected ９９ｍ Tc is altered ９９ｇ Tc, which may render it unusable as a pharmaceutical ingredient.

[0067] On the other hand, in the present invention, the AC contained in the metal mesh cylindrical container 120 is ９９ In a high concentration Mo solution containing Mo ９９ It is a daughter nuclide produced by the decay of Mo. ９９ｍ For Tc ９９ The ratio of the number of Mo atoms is 10 １６ Even if there are more than ９９ｍ Tc can be selectively separated and recovered.

[0068] The metal mesh cylindrical container 120 containing the AC is immersed in the Mo solution, and the Mo solution is stirred to flow around the metal mesh cylindrical container 120. ９９ｍ It is not necessary to adjust the flow rate of the Mo solution to pass it through the AC column, and the Tc is always absorbed from the entire Mo solution present around the metal mesh cylindrical container 120. ９９ｍ Tc is adsorbed by AC, so it ９９ｍ This makes it possible to collect Tc.

[0069] As shown in FIG. 5, a cylindrical metal mesh container 120 containing AC was immersed in the Mo solution. ９９ｍ Tc was adsorbed and collected from AC and purified as a pharmaceutical raw material. ９９ｍThe time required for each step to recover Tc is significantly reduced compared to the conventional method. ９９ Regardless of the radioactivity of Mo, AC is always ９９ｍ Since Tc is adsorbed and collected, the process time required for this is zero. ９９ｍ The time required to purify and recover Tc is approximately 10 minutes, and the process can be performed consistently over a fixed period of time, making this an ideal method for manufacturing pharmaceutical raw materials that require strict quality and shipping arrangements.

[0070] MoO containing a very large amount of Mo (2,500 g) ３ (3,750 g) was dissolved in 6 M (molar concentration mol / L) NaOH (1.75-1.8 L), and then ２ O was added to prepare a Mo solution (10 L) with a pH of 8 to 9. The Mo solution was placed in a 15 L beaker and ９９ｍ 0.1 mg of Re (rhenium) was added as a substitute for Tc (500 Ci). A stainless steel cylindrical metal mesh container (1.6 cm diameter, 6 cm length, 12 cc capacity) filled with AC (4.5 g) was immersed in the Mo solution, and the stirring blade was rotated (30 rpm) in the Mo solution for 6 hours. After stirring, the metal mesh cylindrical container was removed from the Mo container (container containing the Mo solution) and washed with water to remove any Mo remaining unadsorbed in the AC pores. Re adsorbed to AC was then eluted from AC with 1.3 M NaOH (30 mL). The solution was passed through an IER column packed with a strongly acidic cation exchange resin, and then passed through an AL column containing activated alumina (6 g), where Re was adsorbed and captured by the alumina. 20 mL of physiological saline (0.9% NaCl) was passed through the AL column to which Re was adsorbed, and a physiological saline solution (pH 4.8 to 5.2) containing Re was collected.

[0071] In addition, ９９ The half-life of Mo is 65.94 hours. ９９ｍ The half-life of Tc is 6.01 hours. ９９ The amount of Mo (500 Ci) was 1.04 mg, which is 1 / 500,000 of Mo (500 g). ９９ｍThe amount of Tc (500 Ci) was 0.095 mg, which was 5 million times less than Mo (500 g). At the μCi test level, ９９ The radioactivity of Mo is 5 x 10 ４ The weight ratio to Mo (500g) is 6e －１５ is less than ９９ｍ The radioactivity of Tc is 6 x 10 ４ The weight ratio to Mo (500g) is 6e －１６ The results of a wide range (wide range) of radioactivity tests from the μCi level to the 80 Ci level and a non-radioactivity test equivalent to 500 Ci (Mo 500 g or more) TcMM test showed that the separation factor of Mo and Tc by AC (selective adsorption of Tc) was 10 e １６ That was all.

[0072] The amount of Re recovered was 0.092 to 0.096 mg, and the recovery rate of Re was approximately 94%. ９９ｍ Since the Re is equivalent to Tc (500 Ci), a metal mesh cylindrical container filled with AC was immersed in a Mo solution. ９９ｍ It is thought that similar results will be obtained when Tc is adsorbed and collected by AC. ９９ Daughter nuclides produced by the decay of Mo ９９ｍ For Tc ９９ The ratio of the number of Mo atoms is 10 １６ Even if there are more than ９９ｍ This indicates that AC selectively adsorbs Tc.

[0073] According to the present invention, radioactive ９９ A high-concentration Mo solution containing Mo is produced and left for about 24 hours. ９９ From Mo ９９ｍ Tc is generated and mixed in a state of radioactive equilibrium (the ratio of the radioactivity of the parent nuclide to the daughter nuclide is constantly balanced), and instead of passing the solution through an AC column as in the past, an AC-filled metal mesh cylindrical container is immersed in a stirred and flowing Mo solution, so that the ９９ｍ Tc can be captured by adsorption onto AC.

[0074] Whether the amount of high-concentration Mo solution is as small as 0.1 L or as large 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 At the time when the amount of Tc is generated, the target amount ９９ｍ Since Tc is selectively adsorbed and collected on AC, it is particularly effective for Tc with a short half-life (6 hours). ９９ｍ It is effective in recovering Tc.

[0075] The adsorption and collection of AC in a cylindrical metal mesh container ９９ｍ When desorbing Tc, the remaining Mo( ９９ Mo) also ９９ｍ It leaches out at the same time as Tc, ９９ｍ By passing the Tc recovery solution through an alumina column, Mo( ９９ It is free from radioactive impurities such as ZnO, and is of high purity suitable for pharmaceutical raw materials. ９９ｍ Tc can be purified and recovered.

[0076] The adsorption of Mo and Tc onto activated carbon (AC) or aluminum oxide (alumina: AL) is affected by pH conditions. ２ MoO ４ Ya (NH ４ ) ２ MoO ４ For water-soluble Mo compounds such as those mentioned above, the adsorption or desorption to AC or AL can be controlled by changing the pH (from acidic to neutral to alkaline). At low pH (for example, acidic around pH 1 to 5), Mo becomes MoO ２１ ６－ and has the property of being adsorbed and held in large quantities on AC, AL, etc. in the state of Mo oxide with high volume density.

[0077] The method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 involves the following steps: ９９ Mo) was adsorbed in large amounts onto AC or AL to obtain Mo ( ９９ Mo) ９９ｍ Tc is eluted and then purified with AL in the subsequent step. ９９ｍ LSA for purifying and concentrating Tc ９９ Mo / ９９ｍThis system uses a small Tc generator (TcPG), which is a system for purifying and recovering medical technetium-99m from low-specific activity molybdenum-99.

[0078] Na ２ Mo ( ９９ Mo)O ４ When the solution is made low pH (about pH 1 to 5), ９９ Mo-containing Mo oxide polymer (poly-Mo( ９９ Mo(Oxide) is produced and is adsorbed and retained by AC at a rate of about 0.2 g (Mo) / g (AC) or more. ９９ AC or AL (about 5 g in the case of AC: 1.0 to 1.2 g of Mo adsorbed) was packed into a column container and washed with physiological saline (0.9% NaCl solution with pH adjusted with HCl). ９９ｍ For Tc milking ９９ Create a Mo (molybdenum 99) adsorption column.

[0079] The column container is a cylindrical container or the like that is filled with granular material and has a structure that allows the poured liquid to be discharged. ９９ As a method for adsorbing Mo, Mo ( ９９ A cylindrical metal mesh container packed with AC or AL is immersed in a Mo) solution, and a column container packed with AC or AL is immersed in a Mo ( ９９ and a method of passing a Mo solution through the system.

[0080] The previous Mo ( ９９ Mo) adsorption column using weakly acidic aluminum oxide (weakly acidic alumina AL) ９９ｍ Eluting Tc ９９ｍ By installing a Tc (Technetium 99m) purification column, LSA ９９ Mo / ９９ｍ Tc is a small generator.

[0081] ９９ｍ ​There are several methods for producing small Tc generators, including a method that utilizes a sol-gel reaction using heavy metals such as zirconium (Zr) and titanium (Ti), a method that uses a large amount of alumina alone, which has low Mo adsorption capacity, and a method that uses mesoporous alumina (a porous, weakly acidic alumina), which is said to have high Mo adsorption capacity. In contrast to these, the method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 does not use different heavy metals, and is the same as the conventional method. ９９ Mo / ９９ｍ Using Al and light element carbon (C) used in small Tc generators, Mo ( ９９ Mo) High adsorption capacity and purity ９９ｍ LSA with elution and recovery of Tc ９９ Mo / ９９ｍ Tc small generator.

[0082] Mo ( ９９ Even if the specific activity concentration of Mo) changes, the same ９９ Mo ( ９９ Mo) When creating an adsorption column, the amount of AC or AL can be changed. ９９ｍ The Tc purification column was ９９ Mo) eluted from the adsorption column ９９ｍ Purification by temporarily capturing and recovering Tc ９９ｍ Since the Tc concentration is about the same, Mo ( ９９ Mo) Even if the specific radioactivity concentration changes or radioactivity decays within a certain range ９９ｍ It is possible to keep the capacity of the Tc generator constant.

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

[0084] Low specific activity in the first paragraph ９９ Mo adsorbed on AC or AL ( ９９ Mo) adsorption column, AL was used in the latter stage ９９ｍ LSA with Tc purification column ９９ Mo / ９９ｍ The basic structure of the Tc small generator and the flow of the solution will be explained.

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

[0086] Next, a low pH (pH 1 to 5) physiological saline solution was passed through the membrane to detect Mo( ９９ The Mo) adsorption column is washed. The saline solution that flows out during washing is removed as waste liquid. By leaving it as it is for about 24 hours, the Mo( ９９ Mo) adsorbed on the adsorption column ９９ Part of Mo collapsed ９９ｍ Tc is generated.

[0087] Next, low pH (pH 1 to 5) physiological saline was added to Mo( ９９ Mo) adsorption column. ９９ Mo) from the adsorption column ９９ｍ TcO ４ － Since it is eluted, ９９ｍ The solution is passed through a Tc purification column. ９９ｍ Tc purification column ９９ｍ TcO ４ － The waste liquid that flows out is removed.

[0088] Finally, a pH-neutral saline solution ９９ｍ The eluate is passed through a Tc purification column. The initial effluent is removed, but ９９ｍ From the Tc purification column ９９ｍ TcO ４ － is eluted, and then purified. ９９ｍ It is recovered as Tc.

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

[0090] AC may be either crushed coconut shell activated carbon or spherical activated carbon, and has a specific surface area of ​​1000 m ２AL can be any material that has been activated to a Mo adsorption capacity of 1000 kJ / g or more and does not contain eluted impurities. Examples of AL include mesoporous alumina granules with high Mo adsorption capacity and nano-sized porous alumina compacts.

[0091] ９９ The raw material for Mo is not uranium, but low-radioactivity Mo produced from natural isotopes. ９９ The specific radioactivity concentration is preferably, for example, about 0.5 Ci / g (Mo) or more.

[0092] In addition, Mo ( ９９ Mo) at the rear of the adsorption column ９９ｍ Tc purification column ９９ｍ Because it has the function of concentrating Tc, even at low specific radioactivity concentrations (for example, about 0.1 to 0.2 Ci / g (Mo)), Mo ( ９９ Mo) By increasing the amount of AC or AL in the adsorption column, it is possible to obtain a high purity of the desired concentration. ９９ｍ Tc can be recovered.

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

[0094] ９９ｍ Tc purification column ９９ｍ When recovering Tc, 10 to 25 mL of neutral pH physiological saline is used, and it can be obtained with a purity of 95% or more. It has a high purity that can be used for patient diagnosis at points of use such as hospitals. ９９ｍ Tc can be obtained in a short time (about 5 to 20 minutes), and the amount of radioactive waste generated is low and small.

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

[0096] Mo ( ９９ The method for preparing the Mo( adsorption column is as follows: ９９ Mo) solution to apply Mo( ９９ Mo) adsorption method, and Mo ( ９９ Mo) solution was passed through the ９９ There is also a distribution method in which the material is adsorbed with Mo.

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

[0098] In the case of the immersion method, a number of cylindrical metal mesh containers are prepared in which 5 to 20 g of AC or AL is filled in a cylindrical SUS mesh, and the fluidized Mo( ９９ The metal mesh cylindrical container is then removed from the tank and poured into a low pH H ２ Wash with O or saline and Mo ( ９９ Mo) adsorption column.

[0099] In the case of the flow method, Mo( ９９ Mo) solution was introduced, and the outflowing Mo( ９９ The Mo) solution is returned to the tank by a pump. ９９ Mo) adsorption column.

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

[0101] Mo ( ９９ Mo) adsorption column emits strong external radiation (beta rays and gamma rays), so Mo( ９９ The Mo adsorption column is surrounded by a solid shield (such as lead or tungsten). ９９ｍBecause Tc emits only relatively weak gamma rays (141 KeV), ９９ｍ The shielding body such as the Tc purification column may be light.

[0102] LSA ９９ Mo / ９９ｍ The Tc miniature generator includes a supply container for input fluid such as saline, a Mo( ９９ Mo) from the adsorption column ９９ｍ a collection vessel for effluent, such as wash solution, separated from the flow to the Tc purification column; ９９ｍ Purified by removing impurities from the Tc purification column ９９ｍ A Tc collection container is also provided.

[0103] Mo ( ９９ Mo) The inflow liquid to the adsorption column is LSA ９９ Mo solution (pH 1-5), physiological saline solution for washing (low pH), physiological saline solution for elution (low pH), etc. ９９ Mo) The effluent from the adsorption column is ９９ Examples include Mo solution and cleaning solution.

[0104] ９９ｍ The influent for the Tc purification column may be physiological saline (neutral pH). ９９ｍ The effluent from the Tc purification column contained Mo( ９９ Mo) from the adsorption column ９９ｍ Waste liquid from elution of Tc, ９９ｍ From the Tc purification column ９９ｍ Examples include the initial effluent when purifying Tc.

[0105] 10 is a graph showing the effect of pH on the adsorption of activated carbon in the method of purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to the present invention. ９９ｍ Re (rhenium), a homologous element, is used as a substitute for Tc.

[0106] At pH levels between 1 and 5, Mo adsorbs at a maximum of 1.2 g (Mo) / 5 g (AC), while Re adsorbs very little. In other words, it can be seen that at pH levels between 1 and 5, Mo adsorbs strongly to AC, while Re (Tc) does not adsorb.

[0107] ​11 is a graph showing the effect of pH on the adsorption of alumina in the method of the present invention for purifying and recovering medical technetium-99m from low-specific activity molybdenum-99. As with AC, the adsorption rate and amount of Mo are high at pH levels between 1 and 5, while the adsorption rate and amount of Re(Tc) are low.

[0108] FIG. 12 shows the results of a milking test of the method of the present invention for purifying and recovering medical technetium-99m from low specific activity molybdenum-99.

[0109] As shown in FIG. 12(a), Mo( ９９ Mo) from the adsorption column ９９ｍ When the Tc elution procedure was repeated once a day for five days (five times), ９９ｍ The elution rate of Tc was found to be over 90%.

[0110] As shown in FIG. 12(b), ９９ｍ When pH-neutral saline (up to 30 mL) was passed through the Tc purification column, 10 mL of saline ９９ｍ From the Tc purification column ９９ｍ The entire amount of Tc was eluted.

[0111] FIG. 13 shows the results of gamma ray measurement to examine the radiochemical purity of technetium-99m purified and recovered from medical technetium-99m purified and recovered from low specific activity molybdenum-99 according to the present invention. ９９ Mo) adsorption column and elution recovery ９９ｍ The gamma ray spectrum data of the Tc solution showed a radiochemical purity of 96% or more. ９９ｍ It can be seen that Tc is recovered.

[0112] According to the present invention ９９ The Mo production method does not use enriched uranium as a raw material, but uses molybdenum with a natural isotope ratio, which is one of the Mo isotopes that occurs naturally at 24.1%. ９８ Neutron activation of Mo ９８ By the Mo(n,γ) reaction ９９ It is what makes Mo.

[0113] According to the present invention, it is possible to realize a small generator capable of extracting radiopharmaceuticals made from low specific activity radioactive molybdenum-99 and radioactive technetium-99m as a raw material for their labeled compounds at points of use such as hospitals. Under acidic conditions (pH 1-5), Mo (molybdenum-99) adsorbs to AC (activated carbon) or AL (alumina) at a rate of approximately 1 g (Mo) / 5 g (AC or AL), while Tc (technetium-99m) does not adsorb to AC or AL. By utilizing this property, a practical LSA can be realized. ９９ Mo / ９９ｍ This becomes the Tc Portable Generator (TcPG).

[0114] Mo raw material ９８ Mo(n, γ) ９９ In the Mo reaction, ９９ The radioactivity concentration of Mo is extremely low compared to when uranium is used as a raw material, which is a drawback. ９９ Mo / ９９ｍ In the case of small Tc generators, heavy metals such as Zr and Ti were used as Mo adsorbents, which prevented practical application. ９９ Mo adsorption column and ９９ｍ Since the Tc collection and concentration AL column configuration does not use heavy metals, it can be approved with a minor drug change application.

[0115] Mo ( ９９ Mo) depending on the specific radioactivity concentration of Mo ( ９９ By increasing or decreasing the amount of AC that adsorbs Mo (for example, 5 to 30 g / column), ９９ It serves as a tank for storing a certain amount of Mo. ９９ Changed from Mo ９９ｍ Tc is eluted and concentrated and collected on the subsequent AL column, ９９ｍ The amount of Tc milking can be controlled. ９９ Mo) Even if the specific radioactivity concentration increases or decreases within a certain range, the same ９９ｍ LSA capable of generating Tc ９９ Mo / ９９ｍ This becomes the Tc generator.

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

[0117] In the present invention, AL is arranged ９９ｍ The Mo( of LSA (low specific activity of 0.5 Ci / g (Mo) or less) was added to the front of the Tc purification column. ９９ Mo) was adsorbed onto AC or AL at a level of 1 g. ９９ Mo ( ９９ Mo) adsorption columns are required because of the extremely low specific radioactivity (approximately 10,000-fold difference).

[0118] Although the embodiments of the present invention have been described above, the present invention is not limited to these. ９９ Mo) adsorption column and ９９ｍ The AC and AL contained in the Tc purification column are not special. ９９ｍ Sterilization can be performed using a high-temperature dry heat or moist heat autoclave, as specified in the radiopharmaceutical standards for small Tc generators.

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

Claims

A method for separating and recovering a daughter nuclide, technetium-99m, produced by decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low specific activity molybdenum-99, comprising: A metal mesh cylindrical container, which is not a column in which the flow rate is restricted, is filled with activated carbon or alumina, and the metal mesh cylindrical container is immersed in the molybdenum solution, which is acidified to a low pH and stirred to flow, thereby producing a molybdenum-99 adsorption column in which the molybdenum-99 is adsorbed onto the activated carbon or alumina; the technetium-99m produced 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; A pH-neutral physiological saline solution is passed through the technetium-99m purification column to separate and elute the technetium-99m, remove impurities, and then purify and recover the technetium-99m. A method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99. A method for separating and recovering a daughter nuclide, technetium-99m, produced by decay of molybdenum-99 contained in a high-concentration molybdenum solution containing low specific activity molybdenum-99, comprising: the molybdenum solution, which has been acidified to a low pH, is passed through a column container filled with activated carbon or alumina to produce a molybdenum-99 adsorption column in which the molybdenum-99 is adsorbed onto the activated carbon or alumina; the technetium-99m produced 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; A pH-neutral physiological saline solution is passed through the technetium-99m purification column to separate and elute the technetium-99m, remove impurities, and then purify and recover the technetium-99m. A method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99. 　 The molybdenum solution contains the radionuclide molybdenum-99 produced by the neutron capture (n, γ) reaction of the natural isotope of molybdenum.

3. The method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to claim 1 or 2. The amount of the activated carbon or alumina that adsorbs the molybdenum-99 is increased or decreased depending on the specific radioactivity concentration of the molybdenum-99, thereby changing the concentration of the technetium-99m that is separated and eluted from the molybdenum-99.

3. The method for purifying and recovering medical technetium-99m from low specific activity molybdenum-99 according to claim 1 or 2. 　 means for producing a highly concentrated molybdenum solution containing low specific activity molybdenum-99 produced by the neutron capture (n, γ) reaction of the natural isotope of molybdenum; a means for preparing a molybdenum-99 adsorption column in which the molybdenum solution is acidified to a low pH and the molybdenum-99 is adsorbed onto activated carbon or alumina; means for producing a daughter nuclide, technetium-99m, by decay of said molybdenum-99; a means for capturing the technetium-99m by eluting the technetium-99m from the molybdenum-99 adsorption column and passing the eluate through a technetium-99m purification column packed with weakly acidic alumina; and a means for passing a pH-neutral physiological saline solution through the technetium-99m purification column to separate and elute the technetium-99m, remove impurities, and then purify and recover the technetium-99m. A system for purifying and recovering medical technetium-99m from low specific activity molybdenum-99. 　 A cylindrical metal mesh vessel, which is not a column in which the flow rate is restricted, is filled with activated carbon or alumina, and the cylindrical metal mesh vessel is immersed in the molybdenum solution, which is acidified to a low pH and stirred to flow, thereby adsorbing the molybdenum-99 onto the activated carbon or alumina. A molybdenum-99 adsorption column.

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