WO2012039038A1

WO2012039038A1 - Method for production/extraction of tc-99m utilizing mo-99, and mo-99/tc-99m liquid generator

Info

Publication number: WO2012039038A1
Application number: PCT/JP2010/066435
Authority: WO
Inventors: 恵子田上; 弘太郎永津; 滋夫内田; 利光福村; 康久藤林
Original assignee: 独立行政法人放射線医学総合研究所
Priority date: 2010-09-22
Filing date: 2010-09-22
Publication date: 2012-03-29

Abstract

Tc-99m produced from Mo-99 can be collected several times by passing an Mo-99 solution containing Tc-99m through a first column filled with an extraction chromatographic resin to extract and purify Tc-99m and extracting and purifying Tc-99m again using the first column after Tc-99m is generated in the Mo-99 solution.

Description

Method for producing and extracting Tc-99m using Mo-99, and Mo-99 / Tc-99m liquid generator

The present invention relates to a method for producing and extracting Tc-99m using Mo-99, and a Mo-99 / Tc-99m liquid generator, and in particular, technetium 99m, which is in great demand as a radiopharmaceutical, with a small amount of solvent and treatment. The present invention relates to a method for producing and extracting Tc-99m using Mo-99, and a Mo-99 / Tc-99m liquid generator, which can be repeatedly produced remotely over time.

Technetium 99m (Tc-99m, half-life 6 hours), which is used worldwide in the fields of nuclear medicine and diagnostic imaging, is the leading role of over 70% of the radioisotopes used in nuclear medicine. Molybdenum 99 (Mo-99, half-life 66 hours) is a radioisotope called Tc-99m parent nuclide because Tc-99m is generated with the decay of Mo-99. An apparatus (Mo-99 / Tc-99m generator) capable of selectively recovering the generated Tc-99m by adsorbing Mo-99 onto a support such as alumina is commercially available (see Non-Patent Document 1, for example). ).

In a general Mo-99 / Tc-99m generator that is commercially available, a raw material (Mo-99) to be adsorbed on a column has a very high specific activity (carrier-free Mo-99). The manufacturing method capable of supplying such Mo-99 was limited to the ²³⁵ U (n, f) method derived from a nuclear reactor. However, in recent years, a technique for producing Mo-99 by the (n, γ) method or (p, x) method using Mo-98 or Mo-100 as a target material is about to be put into practical use. Since Mo-99 obtained by these methods coexists with Mo-98 or Mo-100 as the target material, the specific radioactivity is remarkably reduced (supported Mo-99). It is impossible to use. The reason is that when Mo-99 is adsorbed to a column used for a generator (usually alumina is used), a large amount of non-radioactive Mo (Mo-98 or Mo-100) present in the surrounding area has an affinity as well. This is because the target Mo-99 cannot be adsorbed with high efficiency. Therefore, in order to solve this problem, it is conceivable to prepare alumina capable of adsorbing a large amount of Mo, or use a column made of another material having high affinity and adsorption amount to Mo.

As a generator using liquid, Non-Patent Document 2 discloses a Dowex (registered trademark) -1 column from a Na ₂ [ ⁹⁹ Mo] MoO ₄ solution obtained from (n, γ) ⁹⁹ Mo produced in a nuclear reactor. Is used to collect Tc-99m using an alumina column and tandem, and Non-Patent Document 3 describes a technique for isolating Tc-99m by solution extraction from Mo-99 derived from highly concentrated uranium. Yes.

In the report that the substance adsorbed to the column is not Tc-99m but Mo-99, and Tc-99m is produced by the so-called generator method, normally, Mo-99 is adsorbed and held on some support, and in that state Manufacture Tc-99m (wait for Mo-99 decay). After elapse of a certain time (about 1 day), using the fact that the produced Tc-99m does not adsorb to the carrier, only Tc-99m is selectively eluted using a solvent such as physiological saline. Measures are taken. Mo-99 has an affinity for the support (column), and no method for obtaining Tc-99m after holding Tc-99m on the column has been reported, except for Non-Patent Document 2.

The technique described in Patent Document 1 uses an alumina column for the adsorption of Mo-99, but the amount of Mo that can be adsorbed by the alumina column is not large. Introducing Mo-99 containing a large amount of Mo-98 or Mo-100 into an alumina column not only increases the amount of alumina but also when Tc-99m is to be recovered (eluted) from the column. A large amount of eluate is required. Therefore, in order to maintain stable Mo-99, for example, in a method in which zirconium and molybdenum are combined to prepare a column, a long processing time of about half a day or more is required to prepare the column. There is an operational problem. As a result, a method characterized by adsorbing Mo cannot be applied to a manufacturing method using a raw material in which a large amount of non-radioactive Mo is mixed. In particular, as long as radioactive materials are handled, it is not desirable to extend the processing time in order to suppress physical attenuation. Therefore, Mo-99, to which this method can be specifically applied, has a problem that it is limited to those obtained from highly enriched uranium.

In addition, the technique described in Non-Patent Document 2 requires irritating and hygroscopic tetrabutylammonium bromide and toxic methyl chloride that needs to be careful of fire, and is inconvenient to handle. There is also a problem from the viewpoint of waste. Further, since MoO ₄ ²⁻ moves together with Na ⁺ , it is necessary to remove Na in the next use of Mo. In particular, when Mo-100 is used as a target material (Mo-99 raw material), the presence of Na is undesirable.

Furthermore, the technique described in Non-Patent Document 3 is used when obtaining Tc-99m from Mo-99 derived from highly enriched uranium, but has versatility applicable even when non-radioactive Mo is mixed. However, since methyl ethyl ketone (MEK) is used for the treatment, in the Mo solution in which the oxidizing agent hydrogen peroxide (which is used when dissolving Mo of the target material) is mixed, the production of ketone peroxide is generated. The risk of explosions is increased. Further, there is a problem that fine control is required in the movement of the solution, and in some rare cases, Mo-99 may be mixed into the Tc-99m solution.

The nuclide that the user wants to use is Tc-99m. The amount of Tc-99m present in the solution is much smaller than that of the raw materials (Mo-100 and Mo-98) used to produce Mo-99.

When adsorption is performed focusing on Mo-99 as in the conventional method, all the Mo isotopes become objects to be adsorbed, so the contamination of non-radioactive isotope Mo derived from the Mo-99 raw material is inevitable. A large amount of support was required, and a long-time treatment was required. In addition, when eluting the target Tc-99m from the large amount of the carrier, a large amount of the eluent is required, and the concentration process required for the eluted liquid also takes a long time. Long-term treatment causes a decrease in the production amount as a result of the physical decay of the radionuclide (Tc-99m half-life = 6 hours), and significantly reduces the production efficiency.

The present invention has been made to solve the above-mentioned conventional problems. By selectively adsorbing Tc-99m, the amount of the Tc-99m carrier can be reduced, and not only the size of the apparatus can be reduced. It is an object of the present invention to make it possible to significantly reduce the amount of solvent and processing time required for separation and purification and to collect Tc-99m multiple times.

The present invention has been made on the basis of the above knowledge, and after extracting and purifying Tc-99m by passing a Mo-99 solution containing Tc-99m through a first column packed with extraction chromatographic resin,
A process for producing and extracting Tc-99m using Mo-99, characterized in that Tc-99m is extracted and purified again by the first column after waiting for the production of Tc-99m in the Mo-99 solution. .

Here, a plurality of the first columns can be provided.

Also, the plurality of first columns can be used sequentially.

In addition, the Mo-99-containing solution can be subdivided and the plurality of first columns can be used simultaneously.

Also, the extraction chromatographic resin can be TEVA (registered trademark) resin.

Further, the effluent from the first column can be passed through a second column packed with a 4-fold cross-linked anion exchange resin to separate and purify Tc-99m.

Alternatively, the effluent from the first column can be neutralized and then passed through the second column.

Further, the 4-fold cross-linked anion exchange resin can be Dowex (registered trademark) 1 × 4 resin.

The present invention also provides a storage tank for a Mo-99 solution containing Tc-99m;
A first column packed with extraction chromatographic resin;
The Mo-99 solution is passed through the first column to extract and purify Tc-99m, and after waiting for the production of Tc-99m in the Mo-99 solution, Tc-99m is extracted again from the first column. The present invention provides a Mo-99 / Tc-99m liquid generator characterized by being purified.

Here, a second column packed with a 4-fold cross-linked anion exchange resin can be further provided downstream of the first column, through which the effluent from the first column passes.

In the present invention in which Tc-99m is selectively adsorbed, the amount of Tc-99m present is very small, so that the amount of Tc-99m carrier can be reduced. This not only reduces the size of the apparatus, but also enables a significant reduction in the amount of solvent and processing time required for separation and purification.

Furthermore, after waiting for the generation of Tc-99m in the Mo-99 solution, it is possible to collect Tc-99m multiple times.

In addition, the carrier (ion exchange resin) used in the present invention can be used a plurality of times, and so-called radioactive substance handling work can be performed remotely, so that the exposure problem of workers does not occur.

Furthermore, since the main parts required for separation and purification are small, a plurality of processing systems can be prepared. For example, by preparing three independent processing systems, it is possible to insure against possible failures (for example, leakage of connection parts or malfunction of valves), and even if one processing system fails, The remaining two processes can reduce the damage to 1/3. Since each system is independent, the time required for the treatment is not extended, and the increase in the amount of solvents to be used is very small because the original amount used is small.

Mo-99-containing solutions (main components are raw materials for producing Mo-99, such as Mo-98 and Mo-100), which have been used as generator nucleophilic solutions, are subjected to an appropriate cooling period. Can be reused. Therefore, especially expensive expensive isotopes such as Mo-100 can be used for the next Mo-99 production, and as a result, the cost required for the production of Tc-99m can be greatly reduced. . Supports (columns) used for separation and purification are originally one-time-use consumables and can be reused. However, even when discarded, the total cost can be ignored.

If Mo-99 and Tc-99m are left unattended, each radioactivity attenuates as shown in FIG. Fig. 1 (B) shows that Tc-99m is squeezed (collected) every day (every 24 hours). Daughter nuclide Tc-99m is gradually produced from the Mo-99 containing solution, and the radioactivity of Tc-99m increases with time, but after 23 hours, the radioactivity of Mo-99 and Tc-99m is balanced. Reach the state. Therefore, Tc-99m can be efficiently obtained by introducing Mo-99 containing Tc-99m into the column and separating it.

On the other hand, since the production of Tc-99m continues from the separated Mo-99, Tc-99m can be obtained again by introducing Tc-99m-containing Mo-99 into the column again after 23 hours and separating the two. it can. Reprocessing is possible until the required radioactivity is obtained.

Although the recovery time for each Tc-99m is 23 hours, it is not limited. For example, if Tc-99m is recovered every 6 hours, which is the half-life of Tc-99m, about 42% of the radioactivity of Mo-99 present at the start is obtained.

Pipeline diagram showing effects of the present invention Pipeline diagram showing the configuration of the first embodiment of the generator section which is the main part of the present invention The figure which similarly shows the example of Mo-99 supply section Pipe diagram showing the structure of the Mo-99 production department, also from the accelerator Similarly time chart of Mo-99 manufacturing department A flow chart showing the processing procedure of the generator unit Similarly time chart of generator section Pipe diagram showing Tc separation and purification unit Similarly time chart of Tc separation and purification section Pipeline diagram showing the overall configuration of the second embodiment of the present invention A flow chart showing the processing procedure of the generator unit Flow chart when adding Tc separation and purification unit Pipeline diagram showing the overall configuration of the third embodiment of the present invention

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

First embodiment of the generator unit 200 is a main portion of the present invention, as shown in FIG. 2, is supplied from Mo-99 production section 100 as shown in FIG. 3, from accelerator Mo-99, ¹⁰⁰ Mo ( p, pn) ⁹⁹ Mo, neutron-derived Mo-99, ¹⁰⁰ Mo (n, 2n) ⁹⁹ Mo, neutron-derived Mo-99, ⁹⁸ Mo (n, γ) ⁹⁹ Mo, reactor-derived Mo-99, ²³⁵ A Tc-containing Mo solution tank 132 in which a Tc-containing Mo solution of U (n, f) ⁹⁹ Mo or Mo-99, ¹⁰⁰ Mo (γ, n) ⁹⁹ Mo derived from a photonuclear reaction is stored; For example, a syringe S1 for supplying a mixed solvent H ₂ O ₂ + NH ₄ and a mixed solvent (H ₂ O ₂ + NH ₄ ) tank 134 and a first column (also referred to as a TEVA column) filled with, for example, 2 mL of TEVA resin 210, ultrapure water tank 211, and example For example, a first nitric acid (HNO ₃ ) tank 212 filled with 8N nitric acid HNO _3, a second nitric acid tank 214 filled with 0.1N nitric acid, for example, and ammonia water ( (NH ₄ OH) tank 216, a third nitric acid tank 218 filled with 1.5N nitric acid, a Tc-containing solution recovery tank 220, and helium (He) in which helium gas for supplying the liquid is stored. It has a tank 222, valves V9 to V17, and piping.

The TEVA resin packed in the first column 210 of the generator unit 200 is a tertiary amine due to its chemical structure, reacts with technetium to become a quaternary ammonium salt, and the adsorption becomes stronger. A tertiary amine organic solvent has the ability to adsorb Tc, but back extraction from the organic solvent is difficult. TEVA resin is preferred because it is infiltrated with a tertiary amine in a silica base and can be used like solid phase extraction.

Here, Mo-99 derived from the accelerator is Mo-99 obtained by causing the charged particles to directly collide with the target material (Mo-100) by the accelerator.

In addition, the neutron-derived Mo-99 collides charged particles with a neutron generation target such as Be using an accelerator, and collides the obtained neutrons with target materials (Mo-98, Mo-100). Obtained and requires an accelerator, a neutron generation target, and a neutron irradiation port.

In addition, in the case of Mo-99 derived from a nuclear reactor, neutrons generated inside the reactor collide with U-235, and as a result, Mo-99 was obtained as a fission product. Irrespective of the enrichment of U-235, it is necessary to irradiate a target having a size equivalent to a fuel rod in the reactor, or irradiation on the outer periphery of the reactor.

Also, Mo-99 derived from photonuclear reaction is obtained by colliding an electron of about 60 MeV with target material Mo-100 to obtain Mo-99, and an electron beam generator and an irradiation port are required.

Regardless of the method, the irradiated target is decomposed after being removed from the irradiation site, subjected to chemical treatment (Mo dissolution), and a large amount of non-radioactive Mo except for those using U-235 as a raw material. The solution contains a small amount of Mo-99 (radionuclide).

An example of an accelerator-derived Mo-99 manufacturing unit 100 is shown in FIG. The Mo-99 manufacturing unit 100 includes a target container 110 to which a charged particle (for example, proton) beam from an irradiation port 108 of an accelerator is irradiated, for example, vertically, and a target material dissolved or suspended in a liquid (referred to as a target solution). A target solution (Mo) tank 112 for supplying (Mo-100) to the target container 110, and a heater H1 for reducing and solidifying the liquid portion in the target solution in the target container 110 , An inert gas for drying (also serving as a pressure source for liquid transport), for example, a helium (He) tank 116 for supplying helium gas, a flow controller 118, and a vacuum pump for promoting evaporation and exhaust (for example, a vacuum pump) and P, a mixed solvent _{_{_{(H 2 O 2 + NH 4}}} OH) tank 122 for storing the recovery solvent, irradiation of the proton beam After the completion, the recovery solvent is introduced into the target container 110 through the pipe 114 by the pressure of the He gas supplied from the He tank 126, and the recovery solvent is re-dissolved. A Tc-containing Mo recovery tank 132 that is introduced from the valve V6 to the target container 110 via the pipe 116, cleans the target container 110, takes out the liquid, and recovers it without discarding, and valves V1 to V8. And

pipes

114, 126, and 128. In the figure, 124 is a solution trap disposed in the middle of the pipe 126 for allowing overflow of the solution from the

target container

110, and 130 is a filter for preventing the clogging of the downstream pipe due to the solid content of Mo. It is.

In the accelerator-derived Mo-99 manufacturing unit 100, as shown in the time chart of FIG. 5, first, the valves V2 and V4 are opened, and the target solution is injected into the target container 110.

Next, the target container 110 is heated by the heater H1, and the valve V5 is opened and sucked by the pump P. Further, the valve V7a side is opened and He gas is introduced for drying to dry the target solution.

Next, the valve V8 is opened, exhausted through the trap 124, and the proton beam R1 is irradiated from the irradiation port 108.

Next, the valve V3 is opened, the solvent is supplied from the H ₂ O ₂ + NH ₄ OH tank 122, the He gas is continuously supplied for stirring, and the heater H1 is turned on to form a solution. During this time, the valve V8 is opened to exhaust from the trap side.

Next, the valves V1 and V7b are opened, and the Tc-containing Mo is recovered in the recovery tank 132.

Further, opening the valve V4 and V6, to supply H _₂ O ₂ + NH ₄ OH from H _₂ O ₂ + NH ₄ OH tank 122 to the target vessel 110, while washing the target container 110, opening the valve V1 and V7b side He gas is then flowed to recover the remaining portion.

Here, the molybdenum solution used as the target solution is obtained by dissolving molybdenum oxide (MoO ₃ is desirable) in 10 to 30% ammonia water. In order to promote dissolution, 10 to 30% hydrogen peroxide water may be added. In this case, the solution composition is preferably 25% ammonia water: 30% hydrogen peroxide water = 1: 1 to 1: 2. .

The above target solution is introduced from the bottom or side of the target container 110. In introducing the solution, a pump or a cylinder can be used. The amount of the solution introduced is determined in advance so that the thickness of the molybdenum compound after crystallization is 0.1 to 5 mm, but the area density of molybdenum is about 450 mg / cm ² or more. .

In drying the solution, heating is performed by the heater H1 fixed to the outer periphery of the target container 110. The set temperature at this time is about 100 to 700 ° C., but 200 to 650 ° C. is desirable. Further, a gas (here, helium gas) is sent into the target container to promote the release of the evaporated water. When the release of moisture is finished, precipitation of ammonium molybdate occurs, but the compound decomposes into molybdenum oxide, ammonia gas, and water by further heating. At this time, ammonia gas and water are released together with the introduced gas to the outside of the target container. As a result, only molybdenum oxide crystals exist on the bottom surface of the target container.

It is desirable to use helium gas as the introduced gas, which is caused by not giving a nuclear reaction product when remaining in the target container 110. Alternatively, it is also preferable to reduce the molybdenum oxide by introducing hydrogen or carbon monoxide. This is because it is possible to increase the molybdenum content per unit volume of the crystals obtained by reduction, and increase the yield of Tc-99m or Mo-99 as a result of increasing the nuclear reaction efficiency. Because it becomes.

As described above, the target substance introduced as a liquid inside the target container is prepared as a solid by drying and solidifying, whereby efficient irradiation becomes possible.

During irradiation, the target container 110 may be a sealed system or an open system. If it is an open system, it becomes possible to prevent the pressure rise resulting from the heat_generation | fever at the time of irradiation, and irradiation without damaging a target container is attained.

After completion of irradiation, ammonia water or a mixed solution of ammonia water and hydrogen peroxide solution is introduced into the target container 110, and the irradiated molybdenum oxide is dissolved again for about 5 to 10 minutes. In order to promote dissolution, warming and mixing by introducing gas are performed.

As liquids to be introduced, ammonia water is used at a concentration of 10 to 30% by weight, and hydrogen peroxide water is used at a concentration of 10 to 30% by weight. The amount of the liquid depends on the shape of the target container, but is 20 to 20% by volume. A liquid volume corresponding to 80% is introduced. As the number of solutions increases, the efficiency with which Tc-99m and Mo-99 that may adhere to a wide range of the target container wall surface can be dissolved and recovered increases.

Next, the molybdenum oxide redissolved solution in which Tc-99m or Mo-99 is dissolved is transferred to the outside of the target container by pumping helium gas or the like. At this time, molybdenum oxide that could not be completely dissolved in the above-described process may block the recovery pipe. Therefore, by providing the filter 130 immediately after the target container and excluding them, stable solution transfer becomes possible. . The filter 130 provided in the middle of the pipe can be a commercially available product having a hole diameter of 0.22 μm or more, and the hole diameter is not limited unless the pipe is blocked. As a filter material, quartz, polypropylene or Teflon (registered trademark) is particularly desirable, but the material is not limited.

In the generator unit 200, the storage of the Tc-containing Mo solution in Step 1000 shown in FIG. 6, the TEVA process in Step 1010, the Mo recovery in Step 1020, and the Tc recovery in Step 1030 are performed.

Specifically, as shown in the time chart of FIG. 7, first, valves V11 and V16 are opened, ultrapure water is supplied from the ultrapure water tank 211 to the TEVA column 210 and discarded from the drain, and then the valve V12 is opened. Then, 8N nitric acid is supplied from the first nitric acid tank 212 to the TEVA column 210 and discarded from the drain, and then the valve V13 is opened to supply 0.1N nitric acid from the second nitric acid tank 214 to the TEVA column 210. Pretreatments 1 to 4 are performed by discarding from the drain. Here, the reason for washing with 8N nitric acid is that, since 8N nitric acid is finally passed, substances that are likely to come out with 8N nitric acid in the final solution are excluded in advance. The reason why 0.1N nitric acid is flowed is to prevent a vigorous neutralization reaction when a target solution containing a mixed solution of alkaline ammonia water and hydrogen peroxide water is added next.

Next, the valves V10 and V11 are opened, the Tc-containing Mo solution in the tank 132 is supplied to the TEVA column 210, the Tc is adsorbed on the TEVA column 210, and the Mo solution is recovered in the Mo recovery tank 132. The water flow rate at this time can be set to, for example, 1-2 mL / min.

Next, the valve V14 is opened and about 4 mL of dilute NH ₄ OH (about 0.01-1%) is supplied, and Mo remaining in the TEVA column 210 is recovered in the tank 132. The water flow rate at this time can be set at, for example, 2 mL / min.

The solution recovered with dilute NH ₄ OH is used for recovery and reuse of Mo. Here, cleaning with dilute ammonia water may be performed with ultrapure water. In this case, the next cleaning with 1.5N nitric acid can be omitted. The purpose of 1.5N nitric acid is to remove as much Mo as possible by the TEVA column 210, and if there is Dowex 1 × 4, it can be omitted.

Next, the valve V13 is opened, and 4 mL of 0.1N nitric acid is passed through the second nitric acid tank 214 to wash the residual Mo. The water flow rate at this time can be set at, for example, 2 mL / min.

Next, the valves V12 and V17 are opened, and, for example, 6 mL of 8N nitric acid is passed through the first nitric acid tank 212, and Tc is eluted from the TEVA resin and recovered. Here, the water flow rate can be set to, for example, 1-2 mL / min. The 8N nitric acid used here is an appropriate concentration / amount that can recover a small amount of liquid and most of Tc, and does not extremely increase the amount of solution when neutralized with sodium hydroxide next time.

Next, after the valves V13 and V16 are opened, 0.1N nitric acid is allowed to flow from the second nitric acid tank 214, and post-treatment 1 is performed.

In the examples, the recovery rate of technetium was 99% or more, and the residual rate of Mo was less than 0.1%.

The Tc-containing Mo generated by the generator unit 200 is separated and purified by, for example, a Tc separation and purification unit 300 as shown in FIG.

This Tc separation and purification unit 300 includes, for example, a second column (also referred to as a Dowex column) 320 packed with 0.75 mL of Dowex 1 × 4, a Tc recovery tank 330, a sodium hydroxide (NaOH) tank 340, It has a pure water tank 342, a first hydrochloric acid (HCl) tank 344, a second hydrochloric acid tank 346, valves V18 to V24, and piping.

Dowex 1 × 4 is a strongly basic anion exchange resin, and therefore technetium, an anion, is strongly adsorbed.

In the Tc separation and purification unit 300, as shown in the time chart of FIG. 9, the valves V20 and V23 are opened, and the ultrapure water in the ultrapure water tank 342 is caused to flow into the Dowex column 320, and the pretreatment 5 is performed. Next, the valve 18 is opened and, for example, 6 mL of 8N NaOH in the NaOH tank 340 is supplied to the tank 220. At this time, water is cooled because neutralization heat is generated. Here, 8N sodium hydroxide is used, but if the specified number is decreased, the amount of liquid increases for neutralization, so that it takes time for separation. Although neutralized with sodium hydroxide, it is made slightly alkaline.

Next, the valves V19 and V23 are opened and supplied to the Dowex column 320 to adsorb Tc and discharged from the drain. The water flow rate at this time can be set to, for example, 1-2 mL / min.

Next, ultrapure water is supplied from the ultrapure water tank 342 at 5 mL, for example, at a water flow rate of 1-2 mL / min to wash the Dowex column 320, and the washing solution is discarded. In this case, ultrapure water is used because hydrochloric acid is continuously poured in, so washing the alkaline column with pure water causes changes in conditions such as generation of neutralization heat when hydrochloric acid is added. It is difficult.

Next, the valve V21 is opened, 1N hydrochloric acid in the first hydrochloric acid tank 344 is supplied at, for example, 5 mL (water flow rate is 2 mL / min), the Dowex column 320 is washed, and the washing solution is discarded. This is to remove Mo eluted from the column by hydrochloric acid treatment before adding 6N hydrochloric acid next time. In addition, if it is okay to overlook mixing of Mo, cleaning with 1N hydrochloric acid can be omitted.

Next, the valves V22 and V24 are opened, and 6N hydrochloric acid is supplied from the second hydrochloric acid tank 346 at, for example, 20 mL (water flow rate is 2 mL / min) to elute Tc from the Dowex 1 × 4 resin, and the Tc recovery tank Collect at 330. Even if the specified number is increased from that of 6N hydrochloric acid, the recovery rate is lowered rather than increased. If the specified number is lower than this, more solution is required to recover Tc.

Next, post-processing 2 is performed by opening valves V20 and V23 and filling the ultrapure water tank 342 with ultrapure water. This is to prevent Dowex from drying, and instead of ultrapure water, a solvent having a reduced salt concentration may be filled.

In the examples, the recovery rate of Tc was 85-88%, and the residual amount of Mo was 1 μg or less. The resulting hydrochloric acid solution is provided after concentration by distillation or neutralization or dilution after neutralization. Even if the total amount of the solution finally reached 0.5 mL, the European Medicines Agency EMA announced on February 21, 2008. It can be less than 2.5 ppm, which is the upper limit of parenteral administration of Mo shown in the published guideline EMEA / CHMP / SWP / 4446/2000.

In this way, after one irradiation, the recovered Mo-100 solution is left for one day, and if the process after TEVA is performed again, Tc can be purified again.

In the embodiment, the TEVA column 210 is a single system, but a plurality of TEVA columns may be provided.

In the second embodiment shown in FIG. 10, a plurality of TEVA columns 210A, 210B,...

The processing procedure of this embodiment is shown in FIG. Step 1002 for determining reuse and step 1004 for selecting a column when not reused are different from the procedure of the first embodiment shown in FIG. When, for example, the column line A is selected in step 1004, all the valves Va shown in FIG. 10 are opened and the pipe line to the column line A is connected. When the column line B is selected, all the valves Vb shown in FIG. 10 are opened and the pipe line to the column line B is connected. )

This embodiment is effective for recovery of Tc particularly considering hygiene when there is a problem with repeated use of the ion exchange resin.

FIG. 12 shows a procedure for further separating and purifying Tc in the second embodiment. The difference from the procedure of the second embodiment shown in FIG. 11 is that step 1022 for performing Dowex processing is added. In this embodiment, when a column is selected in step 1004, a TEVA column and a Dowex column are selected in pairs.

Similarly, the third embodiment shown in FIG. 13 is provided with a plurality of TEVA columns and Dowex columns and a syringe S2 for subdivision, thereby limiting the amount of Mo-99-containing solution flowing into each column. The load on each column is reduced. The syringe S2 can also be used to weigh the minimum amount necessary to obtain the Tc to be used.

This third embodiment is effective for reducing the load on each resin when there is a concern about the radiation resistance of the resin, or for minimizing damage to a failure.

The resin packed in the first column 210 is not limited to TEVA, and the resin packed in the second column 320 is not limited to Dowex 1 × 4.

In addition, tanks for storing the same substances, for example,

helium tanks

116 and 222, mixed solvent (H ₂ O ₂ + NH ₄ OH)

tanks

122 and 134,

ultrapure water tanks

211 and 342, HNO ₃ tanks 212, 214 and 216, HCl tanks. 344, 346, etc. are not separate but common, and may have a predetermined concentration by adjusting the dilution amount as necessary.

Technetium 99m and molybdenum 99, which are in great demand as radiopharmaceuticals, can be repeatedly produced remotely with a small amount of solvent and processing time.

100 (from the accelerator) Mo-99 production unit 112 ... target solution (Mo) Tank 116,222 ... helium (He) Tank 122,134 ... mixed solvent _{_{_{(H 2 O 2 + NH 4}}} OH) tank 132 ... Mo-99 Containing Mo solution tank 200 ... Generator section 210 ... First column (TEVA column)
211, 342 ... Ultrapure water tank ...
212,214,218 ... nitric acid (HNO ₃₎ Tank 216 ... ammonia water (NH ₄ OH) tank 300 ... technetium separation purification unit 320 ... second column (Dowex column)
330 ... Recovery solution tank 340 ... Sodium hydroxide (NaOH)

tank

344, 346 ... Hydrochloric acid (HCl) tank

Claims

The Mo-99 solution containing Tc-99m was passed through the first column packed with extraction chromatographic resin to extract and purify Tc-99m.
A method for producing and extracting Tc-99m using Mo-99, comprising waiting for the production of Tc-99m in a Mo-99 solution and extracting and purifying Tc-99m again with the first column.
The method for producing and extracting Tc-99m using Mo-99 according to claim 1, wherein a plurality of the first columns are provided.
The method for producing / extracting Tc-99m using Mo-99 according to claim 2, wherein the plurality of first columns are sequentially used.
3. The method for producing and extracting Tc-99m using Mo-99 according to claim 2, wherein the Mo-99-containing solution is subdivided and the plurality of first columns are used simultaneously.
5. The method for producing and extracting Tc-99m using Mo-99 according to any one of claims 1 to 4, wherein the extraction chromatographic resin is TEVA (registered trademark) resin.
6. The Tc-99m is separated and purified by passing the effluent from the first column through a second column packed with 4-fold cross-linked anion exchange resin. A method for producing and extracting Tc-99m using Mo-99 according to any one of the above.
The method for producing and extracting Tc-99m using Mo-99 according to claim 6, wherein the effluent from the first column is neutralized and then passed through the second column.
The method for producing and extracting Tc-99m using Mo-99 according to claim 6 or 7, wherein the 4-fold cross-linked anion exchange resin is Dowex (registered trademark) 1 x 4 resin.
A storage tank of Mo-99 solution containing Tc-99m;
A first column packed with extraction chromatographic resin;
The Mo-99 solution is passed through the first column to extract and purify Tc-99m, and after waiting for the production of Tc-99m in the Mo-99 solution, Tc-99m is extracted again from the first column. A Mo-99 / Tc-99m liquid generator characterized by being purified.
A second column packed with a 4-fold cross-linked anion exchange resin is further provided downstream of the first column, through which an effluent from the first column passes. 9. The Mo-99 / Tc-99m liquid generator according to 9.