WO2012039038A1 - Procédé pour la production/extraction du tc-99m en utilisant du mo-99, et générateur de liquides contenant du mo-99/tc-99m - Google Patents
Procédé pour la production/extraction du tc-99m en utilisant du mo-99, et générateur de liquides contenant du mo-99/tc-99m Download PDFInfo
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- WO2012039038A1 WO2012039038A1 PCT/JP2010/066435 JP2010066435W WO2012039038A1 WO 2012039038 A1 WO2012039038 A1 WO 2012039038A1 JP 2010066435 W JP2010066435 W JP 2010066435W WO 2012039038 A1 WO2012039038 A1 WO 2012039038A1
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- 238000000605 extraction Methods 0.000 title claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 31
- 239000007788 liquid Substances 0.000 title claims description 19
- ZOKXTWBITQBERF-AKLPVKDBSA-N Molybdenum Mo-99 Chemical compound [99Mo] ZOKXTWBITQBERF-AKLPVKDBSA-N 0.000 claims abstract description 99
- 239000011347 resin Substances 0.000 claims abstract description 20
- 229920005989 resin Polymers 0.000 claims abstract description 20
- 229920001467 poly(styrenesulfonates) Polymers 0.000 claims description 18
- 239000003957 anion exchange resin Substances 0.000 claims description 7
- 238000003860 storage Methods 0.000 claims description 3
- 239000000243 solution Substances 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 238000000034 method Methods 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 24
- 229910017604 nitric acid Inorganic materials 0.000 description 24
- 238000011084 recovery Methods 0.000 description 20
- 229910021642 ultra pure water Inorganic materials 0.000 description 14
- 239000012498 ultrapure water Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000007789 gas Substances 0.000 description 13
- 238000012545 processing Methods 0.000 description 12
- 238000000926 separation method Methods 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 9
- 235000011114 ammonium hydroxide Nutrition 0.000 description 9
- 239000001307 helium Substances 0.000 description 9
- 229910052734 helium Inorganic materials 0.000 description 9
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 9
- 239000013077 target material Substances 0.000 description 8
- 229910000476 molybdenum oxide Inorganic materials 0.000 description 7
- PQQKPALAQIIWST-UHFFFAOYSA-N oxomolybdenum Chemical compound [Mo]=O PQQKPALAQIIWST-UHFFFAOYSA-N 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- -1 ketone peroxide Chemical class 0.000 description 6
- 238000006386 neutralization reaction Methods 0.000 description 6
- 238000011282 treatment Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- 229910052750 molybdenum Inorganic materials 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 4
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 4
- QOSATHPSBFQAML-UHFFFAOYSA-N hydrogen peroxide;hydrate Chemical compound O.OO QOSATHPSBFQAML-UHFFFAOYSA-N 0.000 description 4
- 239000011733 molybdenum Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 229910052713 technetium Inorganic materials 0.000 description 4
- 229940056501 technetium 99m Drugs 0.000 description 4
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910052770 Uranium Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229950009740 molybdenum mo-99 Drugs 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000009206 nuclear medicine Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940121896 radiopharmaceutical Drugs 0.000 description 2
- 239000012217 radiopharmaceutical Substances 0.000 description 2
- 230000002799 radiopharmaceutical effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- GNENVASJJIUNER-UHFFFAOYSA-N 2,4,6-tricyclohexyloxy-1,3,5,2,4,6-trioxatriborinane Chemical compound C1CCCCC1OB1OB(OC2CCCCC2)OB(OC2CCCCC2)O1 GNENVASJJIUNER-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000022120 Jeavons syndrome Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
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- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
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- 230000004992 fission Effects 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000005078 molybdenum compound Substances 0.000 description 1
- 150000002752 molybdenum compounds Chemical class 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
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- 238000002203 pretreatment Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000012857 radioactive material Substances 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Images
Classifications
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- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
- G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
- G21G1/001—Recovery of specific isotopes from irradiated targets
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
- B01D15/361—Ion-exchange
- B01D15/363—Anion-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J41/00—Anion exchange; Use of material as anion exchangers; Treatment of material for improving the anion exchange properties
- B01J41/04—Processes using organic exchangers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J41/00—Anion exchange; Use of material as anion exchangers; Treatment of material for improving the anion exchange properties
- B01J41/04—Processes using organic exchangers
- B01J41/05—Processes using organic exchangers in the strongly basic form
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J41/00—Anion exchange; Use of material as anion exchangers; Treatment of material for improving the anion exchange properties
- B01J41/20—Anion exchangers for chromatographic processes
-
- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
- G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
- G21G1/001—Recovery of specific isotopes from irradiated targets
- G21G2001/0042—Technetium
Definitions
- 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). ).
- 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.
- a technique for producing Mo-99 by the (n, ⁇ ) 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.
- Non-Patent Document 2 discloses a Dowex (registered trademark) -1 column from a Na 2 [ 99 Mo] MoO 4 solution obtained from (n, ⁇ ) 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.
- 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.
- 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.
- 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.
- MLK methyl ethyl ketone
- the oxidizing agent hydrogen peroxide which is used when dissolving Mo of the target material
- the production of ketone peroxide is generated.
- the risk of explosions is increased.
- 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.
- the present invention has been made to solve the above-mentioned conventional problems.
- 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. .
- a plurality of the first columns can be provided.
- the plurality of first columns can be used sequentially.
- the Mo-99-containing solution can be subdivided and the plurality of first columns can be used simultaneously.
- the extraction chromatographic resin can be TEVA (registered trademark) resin.
- 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.
- the effluent from the first column can be neutralized and then passed through the second column.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- 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
- 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, ⁇ ) 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 ( ⁇ , n) 99 Mo derived from a photonuclear reaction is stored;
- 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.
- 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.
- 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.
- a neutron generation target such as Be using an accelerator
- target materials Mo-98, Mo-100
- 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.
- 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).
- 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 charged particle for example, proton
- a target solution a target material dissolved or suspended in a liquid
- An inert gas for drying also serving as a pressure source for liquid transport
- a mixed solvent (H 2 O 2 + NH 4 OH) tank 122 for storing the recovery solvent, irradiation of the proton beam
- 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.
- 124 is a solution trap disposed in the middle of the pipe 126 for allowing overflow of the solution from the target container 110
- 130 is a filter for preventing the clogging of the downstream pipe due to the solid content of Mo. It is.
- valves V2 and V4 are opened, and the target solution is injected into the target container 110.
- 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.
- valve V8 is opened, exhausted through the trap 124, and the proton beam R1 is irradiated from the irradiation port 108.
- 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.
- the valve V8 is opened to exhaust from the trap side.
- valves V1 and V7b are opened, and the Tc-containing Mo is recovered in the recovery tank 132.
- valve V4 and V6 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.
- the molybdenum solution used as the target solution is obtained by dissolving molybdenum oxide (MoO 3 is desirable) in 10 to 30% ammonia water.
- MoO 3 molybdenum oxide
- 10 to 30% hydrogen peroxide water may be added.
- the above target solution is introduced from the bottom or side of the target container 110.
- 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. .
- 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.
- a gas here, helium gas
- helium gas is sent into the target container to promote the release of the evaporated water.
- ammonia gas and water are released together with the introduced gas to the outside of the target container.
- only molybdenum oxide crystals exist on the bottom surface of the target container.
- helium gas As the introduced gas, which is caused by not giving a nuclear reaction product when remaining in the target container 110.
- 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.
- 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
- 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.
- warming and mixing by introducing gas are performed.
- ammonia water is used at a concentration of 10 to 30% by weight
- 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.
- 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.
- 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 ⁇ m or more, and the hole diameter is not limited unless the pipe is blocked.
- quartz, polypropylene or Teflon registered trademark
- Teflon registered trademark
- 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.
- 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.
- 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.
- 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.
- 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.
- cleaning with dilute ammonia water may be performed with ultrapure water.
- the next cleaning with 1.5N nitric acid can be omitted.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- the valve 18 is opened and, for example, 6 mL of 8N NaOH in the NaOH tank 340 is supplied to the tank 220.
- water is cooled because neutralization heat is generated.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- the recovery rate of Tc was 85-88%, and the residual amount of Mo was 1 ⁇ g 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.
- the recovered Mo-100 solution is left for one day, and if the process after TEVA is performed again, Tc can be purified again.
- the TEVA column 210 is a single system, but a plurality of TEVA columns may be provided.
- 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.
- 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.
- 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.
- step 1022 for performing Dowex processing is added.
- a column is selected in step 1004
- a TEVA column and a Dowex column are selected in pairs.
- 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.
- 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.
- 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
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Abstract
Selon l'invention, le Tc-99m produit à partir du Mo-99 peut être recueilli plusieurs fois par le passage d'une solution de Mo-99 contenant du Tc-99m dans une première colonne remplie d'une résine chromatographique d'extraction pour extraire et purifier le Tc-99m, et l'extraction et la purification à nouveau du Tc-99m à l'aide de la première colonne après que le Tc-99m est généré dans la solution de Mo-99.
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PCT/JP2010/066435 WO2012039038A1 (fr) | 2010-09-22 | 2010-09-22 | Procédé pour la production/extraction du tc-99m en utilisant du mo-99, et générateur de liquides contenant du mo-99/tc-99m |
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PCT/JP2010/066435 WO2012039038A1 (fr) | 2010-09-22 | 2010-09-22 | Procédé pour la production/extraction du tc-99m en utilisant du mo-99, et générateur de liquides contenant du mo-99/tc-99m |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013210226A (ja) * | 2012-03-30 | 2013-10-10 | Sumitomo Heavy Ind Ltd | 99mTcの精製方法 |
JP2020073717A (ja) * | 2012-04-27 | 2020-05-14 | トライアンフTriumf | テクネチウム−99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JPWO2020202726A1 (fr) * | 2019-03-29 | 2020-10-08 |
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JP2005500518A (ja) * | 2001-06-22 | 2005-01-06 | ピージー リサーチ ファンデーション,インコーポレーテッド | 自動放射性核種分離システムおよび方法 |
JP2006075820A (ja) * | 2004-08-10 | 2006-03-23 | Kobelco Eco-Solutions Co Ltd | 排水処理方法及び排水処理装置 |
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JPS516866A (en) * | 1974-07-08 | 1976-01-20 | Pentel Kk | Ionkokanjushinyoru kuromusanhaiekino shorihoho |
JP2005500518A (ja) * | 2001-06-22 | 2005-01-06 | ピージー リサーチ ファンデーション,インコーポレーテッド | 自動放射性核種分離システムおよび方法 |
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Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013210226A (ja) * | 2012-03-30 | 2013-10-10 | Sumitomo Heavy Ind Ltd | 99mTcの精製方法 |
JP2020073717A (ja) * | 2012-04-27 | 2020-05-14 | トライアンフTriumf | テクネチウム−99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JP2022063838A (ja) * | 2012-04-27 | 2022-04-22 | トライアンフ インコーポレイテッド | テクネチウム-99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JP7080873B2 (ja) | 2012-04-27 | 2022-06-06 | トライアンフ インコーポレイテッド | テクネチウム-99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JP7210648B2 (ja) | 2012-04-27 | 2023-01-23 | トライアンフ インコーポレイテッド | テクネチウム-99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JP7644154B2 (ja) | 2012-04-27 | 2025-03-11 | トライアンフ インコーポレイテッド | テクネチウム-99mのサイクロトロン生産のためのプロセス、システム、及び装置 |
JPWO2020202726A1 (fr) * | 2019-03-29 | 2020-10-08 | ||
WO2020202726A1 (fr) * | 2019-03-29 | 2020-10-08 | 国立研究開発法人量子科学技術研究開発機構 | Procédé de production de composés radiomarqués et dispositif de production, composé radiomarqué et dispositif de production de radio-isotopes |
JP7339692B2 (ja) | 2019-03-29 | 2023-09-06 | 国立研究開発法人量子科学技術研究開発機構 | 放射性標識化合物の製造方法及び製造装置 |
US12102694B2 (en) | 2019-03-29 | 2024-10-01 | National Institutes for Quantum Science and Technology | Radiolabeled compound producing method and producing apparatus, radiolabeled compound and radioisotope producing apparatus |
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