EP3264420B1 - Herstellungsverfahren einer fraktion, die ein reines radioisotop von mo-99 enthält - Google Patents

Herstellungsverfahren einer fraktion, die ein reines radioisotop von mo-99 enthält Download PDF

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EP3264420B1
EP3264420B1 EP17178286.5A EP17178286A EP3264420B1 EP 3264420 B1 EP3264420 B1 EP 3264420B1 EP 17178286 A EP17178286 A EP 17178286A EP 3264420 B1 EP3264420 B1 EP 3264420B1
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radioisotope
molybdate
mol
solution
eluate
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EP3264420A1 (de
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Dominique Moyaux
Valéry HOST
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Institut National des Radioelements IRE
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Institut National des Radioelements IRE
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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
    • 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
    • G21G2001/0036—Molybdenum

Definitions

  • a first cell is dedicated to the dissolution of highly enriched uranium targets.
  • the liquid phase containing the soluble fission products of the uranium recovered by filtration, including the radioisotope Mo-99 it is transferred to a second cell in which it is acidified to deplete iodine.
  • the liquid phase containing the Mo-99 radioisotope is loaded on a column of alumina after removal of the iodine.
  • the liquid phase containing the Mo-99 radioisotope recovered following the elution of the alumina column is then transferred through the third cell to the fourth cell where it will be purified on an ion exchange resin and then on activated charcoal.
  • the purification of the Mo-99 radioisotope is therefore carried out in the second cell and in the fourth cell.
  • the alumina resin is washed before elution with a first solution of nitric acid at a concentration of one mol / l, then with water and finally with the aid of a ammonia solution at a concentration of 10 -2 mol / l.
  • the alumina column is then eluted with concentrated ammonia and the Mo-99 radioisotope is recovered in the eluate. According to this document, 90% of Mo-99 is thus recovered in a volume of 2 liters of concentrated ammonia for a quantity of 3 aluminum targets containing highly enriched uranium.
  • the 2-liter concentrated ammonia solution containing the Mo-99 radioisotope is then loaded onto a Dowex column, onto which the Mo-99 radioisotope binds.
  • the column is then washed with water and eluted with a volume of 200 ml of ammonium carbonate (CO 3 (NH 4 ) 2 ).
  • the 200 ml fraction of ammonium carbonate containing the Mo-99 radioisotope is then acidified with 6N sulfuric acid (3 mol / l).
  • the radioisotope of Mo-99 is a substance that is used in nuclear medicine as a precursor to Tc-99 and Tc-99m radioisotopes, hereafter referred to as Tc radioisotopes.
  • the radioisotopes of Tc are produced by Mo-99 / Tc-99 generators in which Mo-99 is attached to an alumina resin. Molybdenum disintegrates to give Tc-99m, which is recovered by rinsing the column (elution) in physiological saline (saline) in the form of sodium pertechnetate (Na + TcO4-). The generator is then eluted in order to recover a solution (called eluate) of activity necessary for the preparation of the products used in nuclear medicine, typically in a sterile manner.
  • Mo-99 / Tc-99 generators in which Mo-99 is attached to an alumina resin. Molybdenum disintegrates to give Tc-99m, which is recovered by rinsing the column (elution) in physiological saline (saline) in the form of sodium pertechnetate (Na + TcO4-). The generator is then eluted in order to recover a solution (called eluate) of activity
  • Technetium 99m is a low half-life isotope, a y-ray emitter. This radioisotope is used in nuclear medicine to perform many diagnoses. Another isotope, technetium 99 (Tc-99), with a longer lifetime, is a source of ⁇ -particles.
  • Radiological toxicity (per unit mass) depends on the isotope, the type of radiation and the half-life of this isotope.
  • Technetium 99m is particularly interesting for medical applications because its radiation is similar to that of X-rays used in conventional radiography.
  • the very short half-life of this isotope conjugated with the relatively long half-life of the Tc-99 isotope son allows it to be removed from the body before disintegrating again. This makes it possible to perform a nuclear diagnosis at the cost of introducing a relatively low dose of radiation into the body (measured in sievert).
  • Metastable technetium 99 (Tc-99m) is the most widely used radioisotope in nuclear medical imaging as a marker. Its physical characteristics are almost ideal for this purpose because the half-life of 6 hours is long enough to follow the physiological processes of interest, but short enough to limit unnecessary irradiation.
  • the Tc-99 eluate for injection must of course have the highest possible purity and therefore, the purity of Mo-99 which will then be fixed on the alumina resin in the Mo-99 / Tc-99 generator must be also be of high purity, especially with respect to molecules which exhibit high activity and a long half-life which can be eluted at the same time as the Tc-99 of the generator.
  • uranium-based targets weakly enriched contain significantly more uranium than highly enriched uranium-based targets and therefore contain significantly more unusable material (up to 5 times more).
  • the present invention therefore aims to overcome the aforementioned drawbacks by meeting the needs to reduce the amount of highly enriched uranium for the production of radioisotopes for medical use while achieving economic feasibility, but also by maintaining the criteria of purity required for radioisotopes for medical use previously achieved in processes using highly enriched uranium.
  • the present invention therefore provides a method as mentioned at the beginning, wherein said enriched uranium targets are low enriched uranium targets and in that the method further comprises, prior to said filtration, an addition alkaline earth nitrate, more particularly strontium, calcium or barium, more preferably barium and sodium carbonate to said basic slurry.
  • the filtration time of the slurry was reduced from 4 to 6 hours to a reduced time of between 30 minutes and two hours, depending on the number of targets involved in the dissolution.
  • this is already significantly high compared to a process using highly enriched uranium-based targets (filtration time typically between 10 and 20 minutes), but represents a possibility of industrial exploitation, which otherwise would not have existed without significantly increasing the production price of the radioisotopes produced by the fission of uranium 235.
  • low enriched uranium targets the solid phase content in the slurry is 5 times higher.
  • these targets are based on aluminum alloy and uranium, especially in the form of UAI 2 , although other alloy forms are also present (such as UAl 3 , UAl 4 , ).
  • Low enriched uranium targets contain less than 20% by weight of uranium 235 relative to the total weight of uranium present in the target.
  • High enriched uranium targets contain more than 90% by weight of uranium-235 relative to the total weight of uranium in the target.
  • the enriched uranium content is proportionately and significantly decreased (by a factor of about 5).
  • the fact of working from alloy, among others UAl 2 increases the density of uranium present in the target, which can clearly improve the production yield, but also provides other impurities, such as, for example, magnesium, which interfere with the production process of Mo-99 radioisotopes for medical use.
  • the increase in the uranium density of the uranium nucleus has forced the replacement of pure aluminum A5 by a harder alloy. Indeed, with this increase in density, when pure A5 is used, the integrity of the targets (and their non-deformation) during their production would not be guaranteed.
  • the contamination of the radioisotope moiety of Mo-99 by the Sr-90 radioisotope is reduced as it precipitates with the carbonate fed to the slurry.
  • This is of considerable importance since the radio-toxicity of the Sr-90 radioisotope is very high by the combination of its long physical period (radioactive half-life: 28.8 years), its high energy beta radiation and its long biological period (bone tropism). It is therefore very important to reduce this impurity to minimize potential long-term side effects in the patient.
  • resin effluent means the mobile phase which passes through the resin and leaves the chromatographic column.
  • the fraction containing the radioisotope of Mo-99 acidified with 6N sulfuric acid is then passed through a column of activated carbon. After fixing on the activated carbon column, the activated carbon is washed with water and the Mo-99 radioisotope is recovered after elution with 100 ml of NaOH at a concentration of 0.3 mol / l. The yield of this operation is about 85 to 90% recovery of the radioisotope for an elution of which already 10% were previously lost.
  • the process according to the present invention by eluting the chromatographic column of alumina with a solution of NaOH on the one hand, but on the other hand, by using an ion exchange column eluted by ammonium nitrate also made it possible to obtain a fraction containing said Mo-99 isotope in a substantially pure manner, while significantly improving the production yield of the Mo-99 radioisotope.
  • the process according to the present invention makes it possible to obtain a production yield of Mo-99 between 85 and 98%, in particular between 85 and 95% relative to the content of Mo-99 contained in the slurry.
  • said ion exchange resin packaged in NaOH is a strong anionic resin.
  • said purification comprises, before said first elution of the molybdate by a solution of NaOH at a concentration of at least 1 mol / l and at most 2 , 5 mol / l and preferably about 2 mol / l, a washing of the column with water which is then recovered in the form of an effluent of said chromatographic column of alumina and / or oxide of titanium.
  • the process comprises a second elution of the alumina chromatographic column with a solution of NaOH at a concentration of at least 1 mol / 1 and at most 2.5 mol / l and preferably about 2 mol / l and recovery of a second molybdate eluate at a period of time between 20 and 48 hours after the harvesting of said first molybdate eluate.
  • the molybdate salts have had sufficient time to transform so that they can be re-eluted and recovered as a product of the process.
  • a titanium oxide chromatographic column makes it possible to improve the adsorption characteristics of the molybdenum salts.
  • Titanium oxide exhibits improved performance (relative to alumina) over Mo-99 in terms of capacity, distribution coefficient (Kd), and yield. These notions of capacity and Kd are important since they make it possible to work with a smaller volume of adsorbent bed, the height of the resin bed being reduced by +/- 50%.
  • titanium oxide makes it possible to collect in a single elution approximately 90% of the previously fixed Mo-99, which represents a gain compared to a conventional elution carried out on a column of alumina typically used for such a process. . For information, this value of 90% was generally reached in two elutions (carried out over two successive days) with the latter adsorbent.
  • said titanium oxide comprises titanium oxide particles having a d 50 of between 10 and 350 ⁇ m, and having a BET specific surface area of between 30 and 300 m 2 / g, preferably greater than 60 m 2 / g.
  • the notation dx represents a diameter, expressed in ⁇ m, relative to which X% of the measured titanium oxide particles are smaller.
  • the BET specific surface area of the titanium oxide particles is the specific surface area of these particles, measured by nitrogen adsorption manometry and calculated according to the BET method.
  • the titanium oxide particles more specifically have a d 50 of between 50 and 150 ⁇ m, more preferably between 70 and 140 ⁇ m, advantageously between 90 and 120 ⁇ m.
  • the titanium oxide particles have a d 95 of between 10 and 525 microns.
  • the titanium oxide particle size distribution is substantially targeted and narrow.
  • said particles of titanium oxide have pores having a diameter, the average pore diameter being between 1 and 30 nm, preferably between 1 and 20 nm, more preferably between 2 and 18 nm. , and more particularly between 4 and 10 nm.
  • the particles of titanium oxide have a pore volume BJH greater than or equal to 0.1 cm 3 / g, preferably equal to or greater than 0.12 cm 3 g, in particular equal to or greater than 0.15 cm 3 / g, or even greater than or equal to 0.20 cm 3 / g, preferably greater than or equal to 0.22 cm 3 / g and more particularly up to 0 , 4 cm 3 / g.
  • pore volume means the pore volume measured by nitrogen adsorption manometry and calculated according to the BJH method.
  • the titanium oxide particles are present in a proportion by weight of at least 50% by weight, based on the total weight of stationary phase. It is also contemplated in the process according to the present invention to use a column containing a mixture of alumina and titanium oxide.
  • the titanium oxide particles have a ratio d 90 / d 10 less than or equal to 120 microns, preferably less than or equal to 80 .mu.m, more preferably less than or equal to 60 .mu.m, advantageously, less than or equal to 50 ⁇ m.
  • the titanium oxide particles have a BET specific surface area greater than or equal to 70 m 2 / g, preferably greater than or equal to 80 m 2 / g, more particularly greater than 100 m 2 / g, particularly preferably greater than 120 m 2 / g, or even greater than or equal to 135 m 2 / g.
  • said titanium oxide is selected from the group consisting of TiO, TiO 2 , TiO 2 .xH 2 O (with x being an integer between 0 and 10), titanium which may be in the crystalline anatase or rutile form, the combinations thereof and mixtures thereof
  • the titanium oxide particles are substantially spherical.
  • said ion exchange resin packaged in water is a weak anionic resin
  • the process comprises further elution of the titanium oxide chromatographic column by flowing the volume of residual water, at a period of time between 20 and 48 hours after harvesting said first molybdate eluate to obtain a molybdate eluate tail.
  • said molybdate eluate tail is recycled during the acidification step.
  • said purification comprises, before said first elution of the molybdate by a solution of NaOH at a concentration of at least 1 mol / l and from plus 2.5 mol / l and preferably about 2 mol / l, washing the column with water which is then recovered as an effluent from said alumina and / or chromatographic column.
  • said nitrate elution of said Mo-99 radioisotope of the ion exchange resin is preceded by a washing step after adsorption of said Mo-99 radioisotope to the water which is recovered and mixed with said effluent. of said ion exchange resin.
  • said step of recovering a fraction containing the pure Mo-99 radioisotope comprises an acidification of said first molybdate eluate and / or optionally said second molybdate eluate and / or said molybdate eluate.
  • molybdate eluate with a sulfuric acid solution at a concentration of at least 1 mol / l and at most 2.5 mol / l and preferably about 2 mol / l, forming an acidified fraction of radioisotope of pure Mo-99 in the form of molybdenum salts and purification on a column of activated carbon, optionally doped with silver.
  • said purification of said acidified fraction of Mo-99 radioisotope on an activated carbon column comprises a step of loading on a column of activated carbon, optionally doped with carbon. silver, a washing step of the resin on which the Mo-99 radioisotope is attached to water and an elution step with a NaOH solution of 0.3 mol / l forming an Na 2 eluate 99 MoO 4 in 0.2 mol / l NaOH solution forming the fraction containing said pure Mo-99 radioisotope.
  • the process further comprises, prior to said acidification step, a step of removing iodine in solution by passing the filtrate on a silver-doped alumina column.
  • the process further comprises acidification of said basic molybdate solution before, during or after removal of iodine, with formation of an acid solution of molybdenum salts
  • said basic solution for producing said basic slurry is made by adding a basic medium containing a solution of caustic soda and a solution of sodium nitrate, said caustic solution having a solution of sodium hydroxide. NaOH concentration greater than 3.5 mol / l, said sodium nitrate solution having an NaNO 3 concentration greater than 3.5, said NaNO 3 concentration being lower than said NaOH concentration.
  • the subject of the invention is also a fraction containing a Mo-99 radioisotope packaged in a 0.2 mol / l NaOH solution having a radioisotope purity of Mo-99 radioisotope greater than 97%, preferably at least 98%, more particularly at least 98.5% of the activity present in the molybdate chemical form of said Mo-99 radioisotope relative to the total activity of said Mo-99 radioisotope; in all its forms in said fraction.
  • said fraction containing a Mo-99 radioisotope is conditioned in a 0.2 mol / l NaOH solution. in sealed bottles, said sealed vials being enclosed in individual shielded containers.
  • the subject of the present invention is also a fraction containing a Mo-99 radioisotope packaged in a 2 mol / l NaOH solution having a radioisotope purity of Mo-99 radioisotope of greater than 97%, preferably of at least 98%, more particularly at least 98.5% of the activity present in the molybdate chemical form of said Mo-99 radioisotope relative to the total activity of said Mo-99 radioisotope. all its forms in said fraction.
  • said fraction containing a Mo-99 radioisotope according to the present invention is conditioned in a 2 mol / l NaOH solution in sealed flasks, said sealed flasks being enclosed in individual shielded containers.
  • the invention furthermore relates to a fraction containing a Mo-99 radioisotope additionally containing additives such as, for example, ammonium nitrate, NaOCI, sodium nitrate and the like.
  • the present invention also relates to a Tc-99 generator derived from a stock solution comprising a Mo-99 radioisotope fraction according to the present invention or obtained according to the process according to the present invention.
  • Low enriched uranium targets contain an aluminum alloy containing uranium.
  • the enriched uranium content relative to the total weight of uranium is at most 20%, and typically around 19%.
  • the low enriched uranium targets are dissolved during a basic dissolution phase in the presence of NaOH (at about 4 mol / l or more) and NaNO 3 (at about 3.5 mol / l).
  • a slurry is formed as well as a gaseous phase of Xe-133.
  • the slurry contains a solid phase consisting mainly of uranium and hydroxides of fission products and a liquid phase of molybdate (MoO 4 - ) and iodine 131 under iodine salts.
  • the volume of the basic dissolution phase increases with the number of targets given the very high content of non-usable product after dissolution of the targets.
  • the dissolution of the aluminum of the target is an exothermic reaction.
  • the gaseous phase of Xenon is recovered by capture using a Xenon retention device or xenon trap.
  • xenon When the xenon is removed, one is then added to the slurry at a concentration of between 0.05 mol / l and 0.2 mol / l and up to a volume of 2 to 6 liters depending on the number of targets.
  • Sodium carbonate is also added at a concentration of between 1 mol / l and 1.5 mol / l, preferably about 1.2 mol / l at 100 to 300 ml depending on the number of dissolved targets.
  • the slurry is then diluted with water to a volume of 2 to 6 liters depending on the number of targets to allow its transfer to the next step.
  • the slurry containing the solid phase and the basic liquid phase is then filtered by means of a glass fiber filter whose porosity is between 2 and 4 ⁇ m, preferably around 3 ⁇ m.
  • two filters are placed in series, to prevent a defect of the first filter and avoid transferring uranium further downstream in the process, to improve nuclear safety.
  • the solid phase is washed twice with a volume of water of 900 ml, recovered and optionally returned upstream of the process for a subsequent acidic dissolution.
  • the filtrate (recovered basic liquid phase containing the fission products Mo-99, I-131, I-133, I-135, Cs-137, Ru-103, Sb-125 and Sb-127) but also aluminate formed by the basic dissolution of aluminum targets, which is soluble at basic pH.
  • Aluminum is soluble in basic medium as well as in acid medium. On the other hand, it is insoluble when the pH is between 5 and 10.
  • the filtrate is loaded onto a silver-doped alumina column to fix the iodine and recover a basic filtrate depleted of iodine-131 and other isotopes of iodine.
  • the silver-doped alumina column is washed with a volume of about 500 ml of caustic soda at a content of about 0.05 mol / l, volume depending on the number of targets, the volume alumina, and other factors.
  • the impregnation rate of the alumina resin contained in the alumina column is about 5.5% by weight.
  • Iodine selectively binds by reaction with the silver doping present on the surface of the alumina to form an insoluble silver iodide.
  • the silver doped alumina column is preferably positioned between two reactors.
  • the reactor downstream of the silver-doped alumina column is placed under a controlled vacuum, which allows the liquid to be transferred to the column at a flow rate of between 150 ml / l and 400 ml / l, more particularly in the vicinity. 250 ml / min.
  • the iodine capture yields are about 95%.
  • the silver-doped alumina column is eluted with a thiourea solution at a concentration of between 0.5 and 1.5 mol / l, preferably about 1 mol / l.
  • the eluate then contains the iodine from the column.
  • the eluate is then brought to acidic pH with the addition of a buffer mixture, in particular phosphoric acid to obtain an acid solution of iodine salts.
  • the activity of the iodine attached to the silver-doped resin is transferred from one cell to another in solid form.
  • the acid solution of iodine salts is then loaded onto an ion exchange column, in particular on a weak anionic resin column previously conditioned in a non-oxidizing acid medium, in particular using phosphoric acid at a concentration of between 0.5 and 1.5 mol / l, preferably about 1 mol / l.
  • the ion exchange column on which the iodine is attached is then eluted with NaOH at a concentration of at least 1 mol / l and at most 2.5 mol / l and preferably about 2 mol / l.
  • radioisotopes of iodine are then converted to iodide and solubilized in NaOH.
  • the fraction containing the radioisotopes of iodine is then packaged in hermetic bottles contained in an armored enclosure for shipment to the customer.
  • the filtrate collected must then be acidified. However, the acidification also causes a release of heat. Therefore, before acidification, the filtrate is cooled to a temperature of about 50 ° C. Indeed, as we know from the document «Form and Stability of Aluminum Hydroxide Complexes in Dilute Solutions (JD Hem and CE Roberson - Chemistry of Aluminum in Natural Water - 1967 ), the behavior of aluminum in solution is complex and the reactions of transformation of the Al 3+ ion into the precipitated form of hydroxide and the soluble aluminate form are subjected to a certain kinetics.
  • the medium is highly radioactive and at a high temperature because of the basic dissolution but also because of the exothermic nature of the neutralization during the acidification step, the addition of acid would form acid overconcentrations at localized locations. causing local heating by the neutralization reaction, and the formation of insoluble aluminum or kinetic forms of slow re-dissolution of aluminum salts.
  • the reaction medium has a high temperature, is highly radioactive and difficult to access, it is not possible to maintain stirring to avoid these points of high temperature aluminate concentration.
  • the filtrate is cooled to avoid precipitation of aluminum salts during acidification at a temperature of about 50 ° C and in all cases less than 60 ° C.
  • the filtrate is thus acidified with concentrated nitric acid.
  • the acidified filtrate is heated to a temperature above 93 ° C, preferably greater than or equal to 95 ° C, preferably between 96 ° C and 99 ° C, but preferably less than 100 ° C and maintained under bubbling.
  • the acidification makes it possible to obtain an acidic pH solution in order to be able to fix the Mo-99 radioisotope on the alumina column (in the presence of an excess of 1M acid).
  • the acidified liquid phase, depleted in iodine, is then loaded onto a column of alumina, conditioned in 1 mol / l nitric acid. Mo-99 is adsorbed on alumina while the majority of the contaminating fission products are removed in the alumina column effluent.
  • the alumina column is then eluted with NaOH at a concentration of about 2 mol / l and then with water.
  • the eluate recovered from the alumina column forms the first eluate of the Mo-99 radioisotope in the form of molybdate.
  • the first eluate of the column is stored for a period of time of between 20 and 48 hours. After this predetermined period of time, the alumina column is eluted again with NaOH at a concentration of about 2 mol / l and then with water before cleaning. The eluate of the new elution forms the second eluate of the radioisotope of Mo-99, in the form of molybdate.
  • either the first eluate of the Mo-99 radioisotope is combined with the second eluate of the Mo-99 radioisotope and forms a single eluate which will further undergo the subsequent purification steps. Either each first and second eluate is treated separately in subsequent purification steps in the same manner.
  • the radioisotope eluate of Mo-99 will now be referred to as the first eluate of the Mo-99 radioisotope or the second eluate of the Mo radioisotope. -99 or both of them together.
  • the radioisotope eluate of Mo-99 from the alumina column is then loaded onto a second chromatographic column containing a strong anionic ion exchange resin pre-conditioned in water.
  • the ion exchange column is then eluted with nitrate using a solution of ammonium nitrate at a concentration of about 1 mol / l.
  • the recovered eluate thus comprises the Mo-99 radioisotope in a fraction containing ammonium nitrate.
  • the ammonium nitrate solution containing the Mo-99 radioisotope is then loaded onto a 35-50 mesh activated carbon column, which may be optionally doped with silver to recover any traces of iodine.
  • the activated carbon column on which the Mo-99 radioisotope is attached is then washed with water and then eluted with a solution of NaOH at a concentration of about 0.3 mol / l.
  • Elution of the activated carbon column makes it possible to recover a solution of Na 2 99 MoO 4 in NaOH but to keep any iodine captured on the column at a preferred concentration of 0.2 mol / l, which will then be conditioned. and packed for delivery.
  • the solution of Na 2 99 MoO 4 in NaOH at a preferred concentration of 0.2 mol / l is loaded onto an alumina resin in a Mo-99 / Tc generator. -99 or on a titanium oxide resin to enable the generation of technetium 99 radioisotope for nuclear medicine.
  • the acidification makes it possible to obtain an acidic pH solution in order to be able to fix the Mo-99 radioisotope on the titanium oxide column (in presence of an excess of 1M acid).
  • the acidified liquid phase, depleted in iodine, is then loaded on a titanium oxide column, conditioned in 1 mol / l nitric acid. Mo-99 is adsorbed on titanium oxide while the majority of the contaminating fission products are removed in the titanium oxide column effluent.
  • the titanium oxide column is then eluted with NaOH at a concentration of about 2 mol / l and then with water.
  • the eluate recovered from the titanium oxide column forms the first eluate of the Mo-99 radioisotope in molybdate form and comprises about 90% or more of the Mo-99 initially present.
  • the elution of the titanium oxide column is continued with water and forms an elution tail containing the radioisotope of Mo-99, in the form of molybdenum salt.
  • said molybdate eluate tail is reintegrated for subsequent production at said first molybdate eluate and forms a pool of eluates which are then acidified with a sulfuric acid solution at a concentration of between 1 and 2.
  • mol / l preferably at 1.5 mol / l, thus forming an acidified fraction of pure Mo-99 radioisotope in the form of molybdenum salts.
  • said first molybdate eluate is acidified with a sulfuric acid solution at a concentration of between 1 and 2 mol / l, preferably at 1.5 mol / l, thus forming an acidified fraction of pure Mo-99 radioisotope in the form of molybdenum salts
  • the Mo-99 radioisotope eluate of the titanium oxide column is then loaded onto a second chromatographic column containing a weak anionic ion exchange resin previously conditioned in water.
  • the ion exchange column is then eluted with nitrate using a solution of ammonium nitrate at a concentration of about 1 mol / l.
  • the recovered eluate thus comprises the Mo-99 radioisotope in a fraction containing ammonium nitrate.
  • the ammonium nitrate solution containing the Mo-99 radioisotope is then loaded onto a 35-50 mesh activated carbon column, which may be optionally doped with silver to recover any traces of iodine.
  • the activated carbon column on which the Mo-99 radioisotope is attached is then washed with water and then eluted with a solution of NaOH at a concentration of about 0.3 mol / l.
  • Elution of the activated carbon column makes it possible to recover a solution of Na 2 99 MoO 4 in NaOH but to keep any iodine captured on the column at a preferred concentration of 0.2 mol / l, which will then be conditioned. and packed for delivery.
  • the solution of Na 2 99 MoO 4 in NaOH at a preferred concentration of 0.2 mol / l is loaded onto an alumina resin in a Mo-99 / Tc generator. -99 or on a titanium oxide resin to allow the generation of technetium 99 radioisotope for nuclear medicine
  • the sealed container comprises a gas phase outlet connected to a recovery device rare gases, isolated from the outside environment, but also an inlet for a flushing gas.
  • the gaseous phase contains ammonia (NH 3 ) from nitrate reduction and the main gaseous fission products are Xe-133 and Kr-85
  • the Xenon recovery is carried out as follows:
  • the gas phase leaves the basic dissolution tight container and is fed to the rare gas recovery device.
  • the gaseous phase containing among others the Xe-133 radioisotope is first passed through a molecular sieve to remove ammonia (NH 3 ) and water vapor.
  • the gaseous phase is passed through silica gel in order to eliminate any trace of residual water vapor.
  • the gas phase is then brought to the cryogenic trap.
  • the gaseous phase is adsorbed on zeolite, in particular on a titanosilicate or on a silver doped aluminosilicate, preferably on Ag-ETS-10 or Ag -chabazite. It will then be marketed directly on the zeolite or desorbed hot and sent to a subsequent retention device.
  • the gaseous phase containing inter alia the radioisotope Xe-133 is thus brought to the cryogenic trap in a U-shaped tube immersed in liquid nitrogen (ie at -196 ° C) contained in a shielded container, through stainless steel shavings.
  • the 316 stainless steel clippings are made from stainless steel rod 316 having a diameter of between 1.5 and 2 cm and a length of between 10 and 20 cm, preferably between 14 and 18 cm, more particularly about 16 cm using a 4-lip burr with a diameter of 16 mm by means of a hydraulic vice.
  • the speed of the milling machine comprising the aforementioned milling cutter is 90 rpm and set with a forward speed of 20 mm / min.
  • the depth of the cutter is about 5 mm.
  • the stainless steel shavings have an average weight of between 20 and 30 mg / shave, preferably between 22 and 28 mg / shave and a non-tapped density when shaped between 1.05 and 1.4.
  • the stainless steel clippings have an average length of 7 mm, a diameter of about 2.5 mm and a thickness of about 1.7 mm.
  • the U-tube comprises a quantity of shavings of between 90 g and 110 g.
  • the volume of 316 stainless steel shavings included in the U-tube is fully immersed in liquid nitrogen.
  • the radioisotope Xe-133 from said gaseous phase containing the radioisotope Xe-133 is then captured by liquefaction of said Xe-133 by means of said cooled stainless steel clippings, which capture the Xe-133 by condensation.
  • the liquefaction temperature of Xe-133 is around -107 ° C. Therefore, Xe gas is condensed in liquid form on stainless steel shavings.
  • the lines are purged and the liquid nitrogen injection is cut off and the trap is brought into contact with a vacuum bulb whose volume is 50 times more large than the volume of clippings contained in the liquid nitrogen trap.
  • the liquid nitrogen trap is then, in closed circuit with the collection bulb, brought to room temperature. After heating 99% of the Xe-133 initially present in gaseous form is found in the ampoule.
  • the acidification of the basic slurry makes it possible to obtain a acidic pH solution that allows the fixation of the Mo-99 radioisotope on the alumina column, the acidification also makes it possible to release the radioisotopes of iodine with a view to their recovery.
  • Recovery of the iodine can then be carried out during and after the acidification of the previously cooled basic filtrate.
  • the radioisotopes of iodine are evolved by heating the acidified filtrate at a temperature above 93 ° C., preferably greater than or equal to 95 ° C., preferably between 96 ° C. and 99 ° C., but preferably less than 95 ° C. 100 ° C and maintained under bubbling to promote the release of iodine in gaseous form.
  • a gas phase which contains the radioisotopes of iodine but also a part of the filtrate which has evaporated.
  • the acidifier has an aqueous phase outlet tubing which dips into a closed container containing water. Another tubing comes out of this closed container. The gaseous phase therefore leaves the acidifier and is bubbled in the water contained in the closed container. In this way, the part of the filtrate which has evaporated is dissolved in the water contained in the closed container, while the insoluble part, namely the radioisotopes of iodine, are found above the surface of the container.
  • the fraction containing the radioisotopes of iodine is then packaged in hermetic bottles contained in an armored enclosure for shipment to the customer.

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Claims (17)

  1. Herstellungsverfahren einer Fraktion, die ein reines Mo-99-Radioisotop enthält, umfassend die Schritte des:
    (i) basischen Lösens von angereicherten Urantargets mit Erhalt einer basischen Aufschlämmung, die Aluminiumsalze, Uran und Isotope enthält, die aus der Spaltung des angereicherten Urans und einer Xe-133-Gasphase stammen,
    (ii) Filterns der basischen Aufschlämmung, um einerseits eine Festphase, die das Uran enthält, und andererseits eine basische Molybdatlösung und Jodsalze zu isolieren,
    (iii) Ansäuerns der basischen Molybdatlösung vor, während oder nach einem Entfernen des Jods, mit Bildung einer sauren Molybdänsalzlösung,
    (iv) Reinigens der sauren Molybdänsalzlösung durch Adsorption der Molybdänsalze an einer Chromatographiesäule,
    (v) Gewinnens der Fraktion, die das reine Mo-99-Radioisotop enthält,
    dadurch gekennzeichnet, dass die angereicherten Urantargets schwach angereicherte Urantargets sind, und dadurch, dass das Verfahren vor dem Filtern weiter ein Hinzufügen von Erdalkalinitrat, insbesondere von Strontium, von Calcium oder von Barium, bevorzugter von Barium und von Natriumcarbonat zu der basischen Aufschlämmung umfasst.
  2. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach Anspruch 1, wobei die Adsorption der Molybdänsalze an einer Chromatographiesäule eine Adsorption an einer Chromatographiesäule auf Basis von Aluminiumoxid ist, und wobei das Reinigen umfasst:
    (a) nach Adsorption der Molybdänsalze an der Aluminiumoxid-Chromatographiesäule, ein erstes Eluieren des Molybdats durch eine NaOH-Lösung in einer Konzentration von mindestens 1 Mol/l und von höchstens 2,5 Mol/l, und vorzugsweise von etwa 2 Mol/l, mit Gewinnen eines ersten Molybdat-Eluats,
    (b) ein Leiten des ersten Molybdat-Eluats über ein in Wasser konditioniertes lonenaustauscherharz, mit Fixieren des Mo-99-Radioisotops und Gewinnen eines Effluenten des Ionenaustauscherharzes, und
    (c) ein Eluieren mit dem Nitrat des Mo-99-Radioisotops in Form von Molybdat vom lonenaustauscherharz durch Zugabe von Ammoniumnitrat, mit Gewinnen des Mo-99-Radioisotops in Form von Molybdat in Nitrat.
  3. Herstellungsverfahren einer Fraktion eines reinen Mo-99-Radioisotops nach Anspruch 1, wobei die Adsorption der Molybdänsalze an einer Chromatographiesäule eine Adsorption an einer Chromatographiesäule auf Basis von Titanoxid ist, und wobei das Reinigen umfasst
    (a) nach Adsorption der Molybdänsalze an der Titanoxid-Chromatographiesäule, ein erstes Eluieren des Molybdats durch eine NaOH-Lösung in einer Konzentration von mindestens 1 Mol/l und von höchstens 2,5 Mol/l, und vorzugsweise von etwa 2 Mol/l, mit Gewinnen eines ersten Molybdat-Eluats,
    (b) ein Leiten des ersten Molybdat-Eluats über ein in Wasser konditioniertes lonenaustauscherharz, mit Fixieren des Mo-99-Radioisotops in Form von Molybdat am lonenaustauscherharz, und Gewinnen eines Effluenten des lonenaustauscherharzes, und
    (c) ein Eluieren mit dem Nitrat des Mo-99-Radioisotops in Form von Molybdat vom lonenaustauscherharz durch Zugabe von Ammoniumnitrat, mit Gewinnen des Mo-99-Radioisotops in Form von Molybdat in Nitrat.
  4. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach Anspruch 2, wobei das in Wasser konditionierte lonenaustauscherharz ein stark anionisches Harz ist.
  5. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach Anspruch 3, wobei das in Wasser konditionierte lonenaustauscherharz ein schwach anionisches Harz ist.
  6. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach einem der Ansprüche 2 bis 5, wobei das Reinigen vor dem ersten Eluieren des Molybdats durch eine NaOH-Lösung in einer Konzentration von mindestens 1 Mol/l und von höchstens 2,5 Mol/l, und vorzugsweise von etwa 2 Mol/l ein Waschen der Säule mit Wasser umfasst, das anschließend in Form eines Effluenten der Aluminiumoxid- und/oder Titanoxid-Chromatographiesäule gewonnen wird.
  7. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach einem der Ansprüche 2 und 4 oder 6, wenn sie von Anspruch 2 abhängen, das ein zweites Eluieren der Aluminiumoxid-Chromatographiesäule durch eine NaOH-Lösung in einer Konzentration von mindestens 1 Mol/l und von höchstens 2,5 Mol/l, und vorzugsweise von etwa 2 Mol/l, und Gewinnen eines zweiten Molybdat-Eluats in einem Zeitraum zwischen 20 und 48 Stunden nach der Ernte des ersten Molybdat-Eluats umfasst.
  8. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach einem der Ansprüche 3, 5 oder 6, wenn sie von Anspruch 3 abhängen, das ein Fortsetzen des Eluierens der Titanoxid-Chromatographiesäule durch Ablaufen des NaOH-Restvolumens in einem Zeitraum zwischen 20 und 48 Stunden nach der Ernte des ersten Molybdat-Eluats mit Erhalt eines Molybdat-Endeluats umfasst.
  9. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach Anspruch 7, wobei das zweite Molybdat-Eluat über ein in Wasser konditioniertes lonenaustauscherharz geleitet wird, mit Fixieren des Mo-99-Radioisotops am Harz und Gewinnen eines Effluenten des lonenaustauscherharzes, und das vor dem Gewinnen der Fraktion, die das reine Mo-99-Radioisotop enthält, weiter ein Eluieren mit dem Nitrat des Mo-99-Radioisotops umfasst, das aus dem zweiten Eluat des Ionenaustauscherharzes stammt, durch Zugabe von Ammoniumnitrat, mit Gewinnen des Mo-99-Radioisotops in Nitrat.
  10. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach Anspruch 8, wobei das Molybdat-Endeluat während des Schrittes des Ansäuerns recycelt wird.
  11. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach einem der Ansprüche 2 bis 9, wobei dem Eluieren mit dem Nitrat des Mo-99-Radioisotops vom lonenaustauscherharz ein Schritt des Waschens nach Adsorption des Mo-99-Radioisotops mit Wasser vorausgeht, das gewonnen und mit dem Effluenten des Ionenaustauscherharzes gemischt wird.
  12. Herstellungsverfahren eines reinen Mo-99-Radioisotops nach einem der Ansprüche 2 bis 11, wobei der Schritt des Gewinnens einer Fraktion, die das reine Mo-99-Radioisotop enthält, ein Ansäuern des ersten Molybdat-Eluats und/oder gegebenenfalls des zweiten Molybdat-Eluats und/oder des Molybdat-Endeluats durch eine Schwefelsäurelösung in einer Konzentration im Bereich zwischen 1 und 2 Mol/l, vorzugsweise von 1,5 Mol/l, wobei eine angesäuerte Fraktion eines reinen Mo-99-Radioisotops in Form vom Molybdänsalzen gebildet wird, und ein Reinigen an einer gegebenenfalls silberdotierten Aktivkohlesäule umfasst.
  13. Herstellungsverfahren eines Mo-99-Radioisotops nach Anspruch 12, wobei das Reinigen der angesäuerten Fraktion eines Mo-99-Radioisotops an einer Aktivkohlesäule einen Schritt des Ladens auf eine gegebenenfalls silberdotierte Aktivkohlesäule, einen Schritt des Waschens des Harzes, an dem das Mo-99-Radioisotop fixiert ist, mit Wasser, und einen Schritt des Eluierens durch eine 0,3 Mol/l NaOH-Lösung umfasst, wobei ein Na2 99MoO4-Eluat in einer 0,2 Mol/l NaOH-Lösung gebildet wird, das die Fraktion, die das reine Mo-99-Radioisotop enthält, bildet.
  14. Herstellungsverfahren eines Mo-99-Radioisotops nach einem der Ansprüche 1 bis 8, wobei die Fraktion, die das reine Mo-99-Radioisotop enthält, eine radiochemische Reinheit von mindestens 97 %, vorzugsweise von mindestens 98 %, insbesondere von mindestens 98,5 %, und in der besonders bevorzugten Weise von mindestens 99 % der in der chemischen Molybdatform des Mo-99-Radioisotops vorhandenen Aktivität aufweist, in Bezug auf die Gesamtaktivität des Mo-99-Radioisotops in allen seinen Formen in der Fraktion.
  15. Herstellungsverfahren eines Mo-99-Radioisotops nach einem der Ansprüche 1 bis 11, wobei der Schritt (III) vor dem Schritt des Ansäuerns einen Schritt des Entfernens von gelöstem Jod durch Leiten des Filtrats über eine silberdotierte Aluminiumoxidsäule umfasst.
  16. Herstellungsverfahren eines Mo-99-Radioisotops nach einem der Ansprüche 1 bis 11, wobei der Schritt (III) ein Ansäuern der basischen Molybdatlösung und von Jodsalzen mit Bildung einer sauren Molybdänsalzlösung und Freisetzung von Jod in Form von Gas im Hinblick auf dessen Entfernen umfasst.
  17. Herstellungsverfahren eines Mo-99-Radioisotops nach einem der Ansprüche 1 bis 16, wobei das basische Lösen, das es ermöglicht, die basische Aufschlämmung herzustellen, durch Hinzufügen eines basischen Mediums ausgeführt wird, das eine Ätznatronlösung und eine Natriumnitratlösung enthält, wobei die Ätznatronlösung eine NaOH-Konzentration von mehr als 3,5 Mol/l aufweist, wobei die Natriumnitratlösung eine NaNO3-Konzentration von mehr als 3,5 aufweist, wobei die NaNO3-Konzentration kleiner ist als die NaOH-Konzentration.
EP17178286.5A 2016-06-28 2017-06-28 Herstellungsverfahren einer fraktion, die ein reines radioisotop von mo-99 enthält Active EP3264420B1 (de)

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BE1030063B1 (fr) 2021-12-22 2023-07-17 Institut Nat Des Radioelements Fup Procédé de production de Molybdène-99

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