JPH06503639A - Production method of soluble irradiation target and radioactive rhenium - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] name of invention Field of invention: soluble irradiation target and method for producing radioactive rhenium The present invention relates to the field of neutron irradiation for producing therapeutic and diagnostic radionuclides. . In particular, the present invention provides improvements for producing rhenium-186 and rhenium-188. related to the irradiation target.

Background of the invention Rhenium isotopes have recently attracted interest in the nuclear medicine community for diagnostic and therapeutic uses. ing. Two rhenium isotopes, namely 186Re and 188Re, have therapeutic and This is especially important because it is suitable for diagnostic purposes. “6Re and 188Re are halved β release with a relatively short period (90 hours for 186Re and 16.98 hours for 188Re) sexual radionuclides (β energy is 1.Q7Mev, 2.12Mev, respectively) It is. Furthermore, both of them have β-emitting properties suitable for β-counters that image biodistribution. (9.2%, 137key and 15% respectively.

155kev).

186Re is converted to 18'Re (37% naturally occurring) by neutron capture in conventional nuclear reactors. It is manufactured from The core properties of this isotopic system are: +s qR,, Punishment -D-+s -5+8608Re (Stable) (N/2 = 90 hours) (Stable) When manufacturing 186Re, metal Rhenium-185 was exposed to 10"-10" neutrons/cm2/ over 24 hours. The irradiation treatment is usually performed at a high neutron flux rate of 1.5 seconds.

After irradiation, the resulting 186Re isotope is conjugated to a tumor-specific antibody, for example. For clinical purposes such as A soluble perrhenate solution is obtained by treatment with hydrogen peroxide or concentrated nitric acid.

A perrhenate solution containing 186Re is then added to the antibody conjugate and/or its must be neutralized and purified to remove contaminants prior to any other clinical use. .

188Re is conventionally produced from natural Reni in the form of carrier addition through neutron bombardment in nuclear reactors. um-187 (63% natural abundance) or preferably concentrated in +86W. Duplex in a neutron flux reactor from a generator made of reduced target tangate material A method of producing 188W and its decay product 188Re by neutron capture. Produced in carrier-free form with high specific activity. The core properties of this isotope system are as follows: That's right: 186W h 187W (JLL-Futaritsu m-ya 188w (stable') (2 3.9 hours) (69.4d) (stable) (16.98 hours) 188Re produced from neutron capture by irradiation of 187R contains non-converted 187R. e and other impurities (i.e. obtained in the form of carrier addition), 188R The short half-life of 188R during relatively long irradiation and subsequent processing steps The tungstate/rhenium generation system by nuclear decomposition limits the e accumulation efficiency. It is highly preferred to produce 188Re in carrier-free form in the system.

Known tungsten/rhenium generators for producing 188Re from the Mina column and a relatively small amount of tungsten target adsorbed on the column. Therefore, the rhenium yield is low, on the order of microcuries (μCi). Ta. To increase the amount of rhenium obtained from such columns (i.e. Curie-m01) Increase the size of the column to accommodate a large amount of target tank. It is necessary to contain gsten. The larger the column, the larger the elution volume. It becomes necessary. Moreover, the known 188W/18 using an alumina column The 8Re generator has a low 188R yield, mainly due to the large amount of (0, 5~2.0g) Target tungsten (mainly +86W) is adsorbed. Due to the need to increase the release or “breakthrough” level of 188Re from the column, There was a problem.

U.S. Patent No. 4.859.931 to Eh+hardl The soluble zirconyl tungstate matrix disintegrates over time to form a matrix 188Re is produced in the form of perrhenate (“’Red4-”), which is easily eluted from the gas. An improved 188Re generator is disclosed. E　h+ha+d+disclosed in patent The zirconium tungstate matrix used is irradiated tungstate trioxide. Sten is dissolved in a heated basic solution, and a base solution is added to an acidic zirconium-containing solution. Acidic tungsten dioxide solution containing 188W was added. A permeable matrix is obtained by obtaining a luconyl slurry and drying this slurry. and filling this matrix into an elution column.

The Ehrha+df generator has proven to be a highly effective 188Re generator. It is.

Direct irradiation of 185Re is effective for producing 18'Re, and direct irradiation of 18FRe Both the zirconyl tungstate generator method is effective for producing 88Re. Although proven, these methods have inherent drawbacks that limit mass production and quality.

For direct irradiation of 185Re or 18'Re, metallic rhenium or rhenium trioxide is used. The irradiated 186Re or +88Re in the form of a film is acidified, typically with concentrated nitric acid. It is solubilized by oxidation and does not form soluble perrhenate (Re04-). Must be. The perrhenate solution is then neutralized, for example with aqueous ammonia. Must be. This method is time consuming and requires complicated processing of the irradiated material. Unwanted by-products that must be separated from the perrhenate as well as essential accompanied by. Known tungsten/rhenium generation methods for producing 188Re Equations can also be used to process irradiated materials, e.g. dissolution, precipitation, filtration, drying, gel micronization, colorization. However, these treatments require metal tungsten or tri-acid. This must be done after irradiation of the tungsten oxide raw material. These for irradiated materials treatment requires complex shielding treatment equipment, resulting in relatively high manufacturing costs. This increases the safety risk.

U.S. Pat. No. 4,778,672 to Deolsch et al. Irradiated perrhenate and and a method for purifying tungstate solutions. By the method of D eutsch etc. dissolves the irradiated metal rhenium by adding concentrated nitric acid and anneals this solution. Neutralize with Monia. This neutralizing solution containing the solubilized perrhenate is then is treated with a soluble lipophilic counterion, e.g. tetrabutyl ammonium bromide. Excessive release from solution is achieved by applying a preferential sorption column that has been pretreated with counterions. Separate the nitrate.

Perrhenic acid separated from unwanted by-products formed during the rhenium dissolution process Let the salt go into solution from the column. This method uses molybdenum-99/technetium-99 Pertechnetate eluent or tungsten-18 obtained from m generation column It can also be used to purify the perrhenium eluate from the 8/rhenium-188 generating column. . The D. eulsch patent method uses pertechnetate and perrhenate solutions. It has been proven that it is effective in removing impurities. However, this method requires a large amount of Time consuming, cost and other issues associated with processing irradiated material are compounded. It's about time.

These problems are particularly acute with respect to the production of 186Re. That is, 186Re has a relatively short half-life and is manufactured by direct irradiation, so it cannot be used in hospital facilities. This is because there are many cases where it is necessary to process the data in an appropriate form.

References related to the production of 99mTc in molybdenum/technetium generation systems. To avoid several processing steps on the shot material, Narasimhan et al. A　New　Zircomolybdate improved in Metpp345-356 Discloses a method for manufacturing a Ni-99”Tc generator, in which the known molybdenum Instead of irradiating molybdenum trioxide like the acid zirconium generation system, Zirconium molybdate by direct irradiation of Zirconium Libdate Precipitation, filtration, drying and atomization of radioactive materials necessary for the preparation of 99″′Tc generator To avoid. However, as reported by Narasimhan et al. Direct irradiation of zirconium produces radioactive contaminants that are unacceptable for therapeutic or diagnostic purposes. For example, 9FZr, 95Zr, 175Hf.

This was accompanied by the production of 18'Hf, ''Na, etc.

Therefore, it facilitates the dissolution of radionuclides or their precursors for diagnostic or therapeutic use. to reduce processing, cost and safety risks for manufacturing in suitable formats. The realization of a radiation target for 186Re and 188Re production with improvements to Highly desired.

Summary of the invention It is water soluble and contains elements that can generate contaminant isotopes unsuitable for therapeutic and diagnostic purposes. direct irradiation of specific water-soluble irradiation targets selected provided that This significantly alleviates the above problems associated with the conventional manufacturing method of 186Re and 188Re. It turns out that it can be reduced. In one embodiment of the invention, aqueous irradiation comprising 18'Re 186Re is produced by directly irradiating the target. preferred target Aluminum perrhenate, lithium perrhenate, perrhenate Magnesium, etc.

In another embodiment of the invention, a soluble aluminum perrhenate comprising 187R; 188R by direct irradiation with lithium perrhenate or magnesium perrhenate It is possible to manufacture e. In still other embodiments of the invention, a Irradiate the soluble irradiation target, dissolve the irradiated target in water, and dissolve it. Insoluble tungsten is produced by reacting the target with an aqueous solution containing zirconyl ions. 18 by forming a zirconyl acid precipitate and placing this precipitate in an elution vessel. A zirconyl tungstate generator containing 188W for 8Re production is obtained. preferred Examples of irradiation targets include sodium tungstate and lithium tungstate. can be mentioned. In any of the examples, the irradiation target is easily dissolved in an aqueous solution. , the complicated melting of irradiated materials inherent in known 186Re and 188Re manufacturing methods. For example, it can be used for diagnostic purposes in the form of a solution after irradiation without any treatment such as decontamination, neutralization, or purification. It can be used for ligand conjugation for therapeutic purposes.

Detailed description of the invention The present invention provides improved rhenium for use in the production of radionuclides 186Re and 188Re. Provide an irradiation target. Preferred irradiation targets that can be used in the present invention are water-soluble and the required radionuclide 186Re or 188R for therapeutic or diagnostic purposes. There are no elements that generate contaminating isotopes at the same time as irradiation that would prevent the use of e. be selected on the condition that The term “soluble” as used here refers to relatively high water It means a compound that has solubility. The soluble irradiation targets of the present invention are at least about It has a water solubility of 1000 g/l, more preferably about 3000 g/l. Ma In addition, the irradiation target has the required 186Re or 188Re radioactivity during irradiation. There are elements that produce radioactive isotopes that interfere with or contaminate the nuclides. Selected on the condition that you do not.

Preferred soluble irradiation target for direct irradiation in 18’Re or “8Re production Aluminum perrhenate, lithium perrhenate, perrhenate Magnesium, etc. The most preferred soluble irradiation target is perrhenate. It is luminium. If the desired radionuclide is 186Re, the irradiation target is +8 Preferably, it is concentrated in 5Re. Similarly, if the desired radionuclide is 188Re, , the target is preferably concentrated in 7Re.

When using lithium perrhenate as the irradiation target. 'By Li Avoiding undesirable by-products associated with neutron capture, such as tritium Therefore, the target is also concentrated in 7Li. 188W for 188Re production The preferred target for use in tungsten/rhenium generators containing There are sodium tungstate, lithium tungstate, etc. Sodium is most preferred. A particularly preferred target is concentrated in 186W and If it is made of lithium, it will also be concentrated in 7Li.

The soluble irradiation target of the present invention is metal rhenium, metal tungsten, or tri-acid. It is obtained by melting rhenium chloride or tungsten by a known method.

For example, rhenium metal can be dissolved in a concentrated acid or hydrogen peroxide solution; Gusten can be dissolved in concentrated nitric acid or hydrofluoric acid. This acidic mixture is then Drying removes undesirable components such as HF (if present). Let it evaporate and add water again to make an aqueous solution.

This solution containing perrhenate or tungstate is added with the required counterion. Mix with aqueous solution. This mixed solution is heated and dried to form a dry form of soluble irradiation target. Collect the waste. If necessary, the irradiation target can be redissolved, for example in water, and filtered. It is purified by filtration, heat-dried, and washed once or several times to further refine the target. You can also refine it. The recovered solid material is directly exposed to neutrons in a known manner. Just irradiate it.

The present invention irradiates water-soluble irradiation targets containing Re or 187Re, respectively. improved radionuclides consisting of the step of dissolving the irradiated target in an aqueous solution. Also provided is a method for making the seeds 186Re or 188Re. Metal reniform as known method direct irradiation of water-soluble irradiation targets rather than irradiation of rhenium or rhenium trioxide. By irradiating the irradiated material, which is inherent in traditional rhenium radionuclide production The complicated purification and processing required is significantly reduced.

The present invention uses sodium tungstate or lithium tungstate containing 186W. The irradiated soluble target containing 188W is tungstate is obtained and this soluble tungstate is reacted with an aqueous zirconium solution. to obtain an insoluble zirconium tungstate gel or matrix, and then The process consists of placing this zirconium tungstate gel in an elution vessel. We also developed an improved tungsten/rhenium generator for 18’Re production. provide. The generator of the present invention produces known zirconyl tungstate gels. ・It is much more advantageous than the production method using a matrix type generation system. because directly irradiates the soluble irradiation target and easily solubilizes the zirconium ions. Forms an insoluble zirconium tungstate gel by reacting with By filling the column, the irradiation required by the production method using the known generation system can be avoided. Avoids cumbersome nitric and hydrofluoric acid dissolution and purification steps for finished materials Because you can. Soluble irradiation targets are dried into solid forms convenient for direct irradiation. It is preferable to do so.

After irradiation, if present, 187W (half-life 24 hours) and 24Na (half-life The irradiated target is preferably allowed to disintegrate from the irradiated material for 15 hours). Dissolve it in water, make it insolubilized by reacting it with, for example, zirconyl nitrate, and fill it into a column. highly soluble ions, including 18'Re, typically in excess nitrate (188Re04-) is formed. Is this 188ReO4- a column? It can be easily eluted from

In this generator embodiment, the zirconium tungstate matrix is The perrhenate containing 188Re is eluted and collected. suitable container For example, glass cartridges such as those used in standard chromatography ram, suitable lead shielding, associated lead piping, and eluent tank. It forms a generator assembly by being wrapped in a “shell” containing Sterilized after each elution run Separate tanks may also be used. Although not a requirement, a matrix is always included. It is desirable to keep it in a water state. Use a suitable eluent such as water or saline It is advantageous to periodically elute the daughter radionuclide. A particularly preferred eluent is It is physiological saline.

The performance of the improved generator of the present invention can be expressed in terms of its elution efficiency. The elution efficiency is The radioactivity level of the daughter radionuclide present in the eluent is determined in the generator column immediately before elution. It can be calculated by dividing by the radioactivity level of the daughter radionuclide present. Ru. The radioactivity of radionuclides can be measured using germanium detectors and germanium detectors that can measure low-level radioactivity. A gamma spectrophotometer, such as a sodium iodide scintillation spectrophotometer, or or standard radioactivity such as a dose caliprator that can measure high levels of radioactivity. It can be measured using a radiation measuring instrument. In the present invention, if the generator is a small column or The entire column is placed inside the dose caliprator and the column is The radioactivity of daughter radionuclides can be directly measured in the column after elution. By subtracting the amount of radioactivity of the daughter radionuclide present in the eluent from this value, The amount of radioactivity of radionuclides can be calculated. In this method, the dose caliprator If set appropriately, the radioactivity measured in the column can be attributed to the daughter radionuclide. Because it is possible to obtain very close values for the daughter radionuclides present in the eluent, It will be done. Elution efficiency is typically measured after approximately 3 to 10 daughter radionuclide half-lives. . Using the generator of the present invention, a high elution efficiency of 55% to 65% can be obtained. The 188Re concentration in the synerte is measured immediately after elution and typically after 3 or 4 half-lives. and 30+nCi/ml or more.

Radiochemical purity of daughter radionuclide using non-radioactive perrhenate as standard Ion exchange reverse phase high performance liquid chromatography (HPLC) or scintillation It can be evaluated by tar chromatography.

During the elution process, a certain amount of the parent radionuclide is transferred to e.g. zirconium tungstate. There is a risk that the particles may be released into the eluent in the form of fine particles and contaminate the daughter radionuclides.

Porous materials such as fritted glass disks used in chromatography columns To some extent, such particles can be eliminated by utilizing glass or plastic structures. This can prevent tungsten from entering the eluent.

However, if the manufacturing method of the present invention is adopted, the parent radiation contained in the generator matrix Most of the generator matrix dissolves before a significant portion of the sex nuclides are released. Therefore, the amount of parent radionuclide released from the column is relatively small (0%). Ma In addition, the level of the parent radionuclide present in the eluent is determined by the amount of adsorption that can absorb the parent radionuclide. by using a medium such as an alumina column or a zirconium hydroxide bed. The eluent from the generator can be purified by an order of magnitude. That is, the origin of the present invention In addition to the container surrounding the generator matrix, the raw system removes the emission 188W. A chromatograph surrounding a second matrix containing a tungsten-specific matrix. A second elution vessel, such as a column, can be included. Or tungsten An adsorbent is placed below the zirconium tungstate matrix that can absorb into the generator column and pass through the tungstic acid matrix, then The eluent may be configured to pass through the adsorbent. Tungsten absorbent adsorbent Another advantage of using matrix particles is to minimize the loss of matrix particles and reduce waste. It is possible to reduce the amount of eluent containing contaminant particles that must be removed. .

The 188W/188Re generator of the present invention is extremely compact, and the generator mat A small amount of lix is fine. 188W is approximately 1 curie (Ci) due to neutron capture Since it can be manufactured with a specific radioactivity of more than /g, if the manufacturing method of the present invention is used, the volume is only 5. A small (Curie size) generator column of ml can be constructed.

The content of the above explanation will become clearer in connection with the experimental examples described below.

However, these experimental examples are for illustrative purposes only and do not limit the concept of the invention. It is not a promise.

Carefully add 0.1 ml of concentrated nitric acid to the beaker containing 50 mg of metal rhenium. Pipette injected. After 2-3 minutes add 0.1 m of 1:1 v/v concentrated nitric acid to the reaction mixture. : Aqueous solution was added and the mixture was allowed to react at room temperature for 20 minutes.

To this mixture was added 0.5 ml of water, then (1.2 ml of 0.447M chloride) Aluminum solution was added. The mixture was heated to 95°C for 12 hours and dried. Dry. Add 1 ml of water to the beaker to dissolve any remaining solids and filter the solution. passed. The filtrate was dried by heating to 95°C for 12 hours to form a white solid filter. Aluminum umate was obtained.

Table 1 shows the elemental analysis of A1 and Re.

Procedure N012 0.5 ml of 30% H20□ solution was carefully added to 50 mg of metal rhenium. . After 10 minutes, 1.5 ml of water was added to the mixture and the mixture was stirred for 30 minutes. Heated to 5°C.

Add 0.2 ml of 0.447M aluminum chloride solution to the mixture and was heated and dried at 95° C. for 12 hours. Dissolve the solids by adding 1-ml of water. Dissolved and filtered the solution. The filtrate was heated and dried at 95°C for 12 hours to give a white color. Solid aluminum perrhenate was obtained.

Procedure N013 50 mg of rhenium metal was carefully pipetted with O and 1 ml of concentrated nitric acid. 2 After ~3 minutes, 0.1 ml of 1:1 v/v concentrated nitric acid, water solution was added to the reaction mixture; This mixture was allowed to react for 20 minutes at room temperature. 0.1ml to the reaction mixture of ammonium hydroxide (conc.) was added, followed by 0.5 ml of water. solid Heat the mixture to 95°C until all remains are dissolved, add 0.2 ml of 0.4 A 47M aluminum chloride solution was added. This solution was heated at 95°C for 12 hours. It was heated and dried. Then 1. Add ml of water to dissolve the solids and filter the solution. Ta. Finally, the filtrate was heated and dried at 95°C for 12 hours to form a white solid perrhenium. Acid aluminum was obtained.

Step No. 4 The procedure described in Procedure N091 was followed. However, step no.

50 mg concentrated Re-185 metallic rhenium in place of natural metallic rhenium in 1. (95%Re-185, I5ojec, Inc, Daylon, 0hio) was used.

Step No. 5 The procedure described in Procedure No. 2 was followed. However, step no.

75 mg concentrated solution in place of the naturally occurring metal rhenium and aluminum chloride solution in 2. Reduced metal rhenium (95% Re-185, Iso+ec, Inc, Da ylon, 0hio) and 0.3 ml of 0.477M aluminum chloride solution It was used.

Procedure N006 The procedure described in Procedure N003 was followed. However, step no.

50 mg of concentrated Re-185 metal rhenium in place of the naturally occurring metal rhenium in 3. (95%Re-185, I5otec, Inc, Da71on, 0hio) was used.

Step Nos, the products of 1-6 were diluted 1:200 in 2 ml of water and As a result of analyzing the aluminum and aluminum content of the sample, the unit is μg/ml. It was found that it contained rhenium and aluminum in the amounts shown in Table 1 below.

Front work Element content (μg/m1) AI 5.0 5.2 5.4 5.1 7.6 4.5Re total amount 125.8 116.7 131.4 104.6 157.4 103.6Re-185 46,142,648,197,714g, 497.5Re-18779,7 74,183,27,29,06,lRe-Al ratio 25.2 22.4 24, 3 20.5 2G, 7 23.0 The excess obtained by steps 4, 5 and 6 of Example ■ A 0.24 mg sample of aluminum rhenate was flame sealed under vacuum. It was sealed in a quartz irradiation field. Unive+5it7 of Misso u+i Re5ea+ch Reactor (Columbia, Mis+o 3X10" neutrons/cm2/se for 1.2 to 14 days at Irradiation was carried out in the fluff of c. Open the irradiation bottle and remove the irradiated aluminum perrhenate. The mixture was dissolved in 0.5 ml of water. The average activity recovery was found to be over 90%, and the activity was ( According to reverse phase HPLC), it takes the form of 186ReO4-, which is the same as 186Re. determined (by germanium lithium analyzer).

0.29g of 186WO3 (96%+86W) in a 5ml beaker.

Oak Ridge National Labo+ato+7. Oak R idge.

Add 0.5 ml of 5N NaOH solution to The mixture was heated to dissolve 186wo. Once dissolution is complete, allow the mixture to cool to room temperature. The pH was adjusted to 9 by adding 5N HCI and IN HCI.

This solution was dried by heating to obtain 0.292 g of white solid sodium tungstate. Ta.

20 m of tungsten sodium (W-186) prepared by the procedure of Example ■ g samples were enclosed in a frame-sealed quartz irradiation field under vacuum. irradiation bottle For 7 days, Universif7 oI Missou “i Re5e” 3X with a “ch Reacjo+ (Columbia, Missouri) Irradiated in a flux of 10" neutrons/cm2/sec. 187W and "N a was disintegrated from the irradiated material. Next, open the irradiation bottle and remove the irradiated tungsten. Sodium chloride was dissolved in 1 ml of water. Filter this solution through a 0.2 μm filter. Filtered. As a result of measuring the activity recovery, it was 95% or more.

Example 40 mg of irradiated sodium tungstate prepared as described in It was dissolved in ml of water and filtered through a 0.2 μm filter. 4ml of 820 to 200 A solution containing mg of naturally occurring Na2WO4 was added to the filtrate to remove insoluble tungsten. Accelerated precipitation of acid salts. Then, 312 mg of ZrO in 5 ml of HCI solution Add tungstate solution to pH 1 acidic zirconyl solution containing (NO3)2. dripped.

The pH of the resulting zirconium tungstate mixture was 6.0. mixture Filter and wash with 50 ml of water.

The gel precipitation yield (% of 188W initially present in the gel) was greater than 95%. Ta. The filtered gel was air-dried overnight, packed into a known generator column, and placed in saline. Eluted with brine. The elution yield of the zirconyl tungstate generator was 66%. .

Although the invention has been described in connection with a preferred embodiment, various modifications are possible. This will be obvious to those skilled in the art.

All such modifications, unless precluded by prior art, are covered by the claims below. shall be included in the

international search report Continuation of front page (72) Inventor: Hsu, Fumin Washington State, 98125, United States.

Treat 3254 (72) Inventor: Erhard, Geary Jay, USA, 65203 Country Hill Road, Columbia, Missouri

Claims (12)

[Claims] 1. Production of rhenium-86 or rhenium-188 radionuclides for therapeutic or diagnostic purposes In this method, radionuclides or their Obtain the parent isotope of The method is characterized by a step of dissolving the irradiated target in an aqueous solution. manufacturing method. 2. The irradiation target is aluminum perrhenate, lithium perrhenate, or perrhenate. Magnesium nitrate, sodium tungstate and lithium tungstate The method according to claim 1, characterized in that the method is selected from the group consisting of: 3. the radionuclide is 186Re, the irradiation target includes enriched 185Re, Aluminum perrhenate, lithium perrhenate and magnesium perrhenate The method according to claim 1, characterized in that the method is selected from the group consisting of: 4. characterized in that the irradiation target contains concentrated 7Li in the form of lithium perrhenate The manufacturing method according to claim 3, wherein: 5. the radionuclide is 188Re, the irradiation target contains enriched 187Re, Aluminum perrhenate, lithium perrhenate and magnesium perrhenate The method according to claim 1, characterized in that the product is selected from the group consisting of: 6. The radionuclide is 188W, the irradiation target contains 186W, and tungsten selected from the group consisting of sodium thenate and lithium tungstate. The manufacturing method according to claim 1, characterized in that: 7. The dissolved irradiated tungstate is reacted with an aqueous solution containing zirconyl ions. tungstate to form an insoluble zirconyl tungstate precipitate. For 188Re production by filling the elution vessel with zirconyl stenate precipitate. 7. The product according to claim 6, further comprising the step of obtaining a radionuclide generator of Law. 8. Aluminum perrhenate, lithium perrhenate and magne perrhenate irradiate a water-soluble irradiation target selected from the group consisting of of rhenium-186, comprising the step of dissolving rhenium-186 in an aqueous solution. Manufacturing method. 9. Concentrating the irradiation target in rhenium-185 or rhenium-187 A manufacturing method characterized by. 10. A claim characterized in that the irradiation target is aluminum perrhenate. The manufacturing method described in item 9. 11. Selected from the group consisting of sodium tungstate and lithium tungstate. The selected water-soluble irradiation target is irradiated, and the irradiated target is immersed in zirconium water. Obtain an insoluble zirconium tungstate gel by reacting with a solution, By filling zirconium tungstate into an elution vessel and eluting the gel. Rhenium-18 characterized by comprising a step of recovering rhenium-188 8 manufacturing method. 12. A claim characterized in that the irradiation target is tungsten sodium. The manufacturing method according to item 11.