CN116648759A - Method for producing radionuclides of high purity and high specific activity - Google Patents
Method for producing radionuclides of high purity and high specific activity Download PDFInfo
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- CN116648759A CN116648759A CN202180082510.6A CN202180082510A CN116648759A CN 116648759 A CN116648759 A CN 116648759A CN 202180082510 A CN202180082510 A CN 202180082510A CN 116648759 A CN116648759 A CN 116648759A
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- 238000000746 purification Methods 0.000 claims description 6
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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
- G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
- G21G1/10—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators by bombardment with electrically charged particles
-
- 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
- G21G2001/0089—Actinium
-
- 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
- G21G2001/0094—Other isotopes not provided for in the groups listed above
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- General Engineering & Computer Science (AREA)
- High Energy & Nuclear Physics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a method for preparing a radionuclide with high specific activity, which comprises the following steps: a) irradiating the target of interest with a particle beam to obtain an irradiated target comprising the radionuclide of interest, b) chemically extracting a batch of the radionuclide of interest from the irradiated target, c) mass separating the radionuclide of interest to obtain a radionuclide of high specific activity.
Description
Technical Field
The present invention relates to the field of producing radionuclides of high purity and high specific activity (for example for medical use on an industrial scale).
Background
Radioisotopes, or radionuclides, are widely used in the fields of life sciences, research and medicine, for example in nuclear medicine.
In nuclear medicine, they are used for diagnostic imaging and radiotherapy, in particular for cancer. To achieve the target, the radioisotope can be attached to a molecule/vehicle, injected into a solution (e.g., citrate) or used alone (Zimmermann, nuclear Medicine: radioactivity for Diagnosis and Therapy-2017-EDP Science Edition).
The radionuclides can be bound to the vehicle (vector) using a chelate (linker) and a linker (linker). A chelating agent (chelating agent) is a substance that can form multiple bonds with a single atom or ion, also defined as a multidentate ligand. When using a vehicle, a suitable biological target must be found in order to bind to tumor cells while not interacting with healthy cells. This can be achieved by using peptides or antibodies with preferential uptake of specific receptors, and by selecting target receptors more common in tumor cells than healthy cells. Radioisotopes that ensure imaging and labeling of the same vehicle (preferably a peptide or antibody) are defined as theranostics (or theranostics) radioisotopes (Langbein et al J Nucl Med.2019Sep;60 (Suppl 2): 13S-19S).
One such important application of radioisotopes is in the diagnosis and treatment of diseases such as cancer. For example, considerable progress has been made in the past two decades in the use of radiolabeled tumor-selective peptides and monoclonal antibodies in the diagnosis and treatment of a variety of cancers. The concept of focusing cytotoxic radionuclides at cancer cells is an important complement to the traditional form of radiation therapy. In theory, the interaction of the radiopharmaceutical with the target cells concentrates the absorbed radiation dose at the location of the cancer cells, thereby minimizing damage to normal surrounding cells and tissues (Zhejiang et al univ Sci b.2014oct;15 (10): 845-863;Zukotynski et al.Biomark Cancer.2016;8 (Suppl 2): 35-38). The basis for the selection of the radioisotope is the nature of the emitted radiation, its physical properties (i.e. energy, half-life and decay chain) and its chemical nature. Depending on the radiation emitted, the radioisotope can be classified as a gamma emitter, a beta (positron beta+ or electron beta-) particle emitter and an alpha particle emitter, an auger emitter, or a combination thereof. Further developments in the nuclear medicine field will require exploration of the use of new isotopes, and new sources and methods of isotope production.
Three main direct or indirect nuclear methods leading to the production of the desired radioisotope can be defined as the production method of the radionuclide and are identified as: nuclear reactions by using particle accelerators (such as cyclotrons, linear accelerators, and electron accelerators); nuclear reactions performed within a nuclear reactor; production of the selected radioisotope obtained by a chemical elution process carried out in a so-called generator. In addition, the production method can be combined with other technologies to improve the quality of the product.
Radioisotopes can be produced by nuclide conversion by bombarding a target nucleic with charged particles (mainly protons, deuterons or alpha particles). These charged particles need to be accelerated to an energy of at least a few MeV to overcome the Coulomb barrier (Coulomb barrier) of the target and allow nuclear reactions to occur. Therefore, a particle accelerator is required. Due to its practical characteristics and high current performance throughout the energy range of interest (10-100 MeV), cyclotrons have been the almost unique choice as the most convenient option for radioisotope production since the 1950 s, except for some therapeutic radionuclides that are more convenient to produce in nuclear reactors. However, only some radioisotopes can be produced in cyclotrons with high radionuclide purity and in high yields (yield). To increase the availability of some other nuclides, for example, US20170169908A1 describes the use of a 70MeV cyclotron and an online mass separation system, even if the target is irradiated with the cyclotron simultaneously or quasi-simultaneously and the latter is separated with an online mass separator to produce the radionuclide. However, these methods imply limitations on the target to be irradiated, i.e. they must have defined characteristics (e.g. porosity, evaporation temperature, etc.) that may reduce the overall yield, and limit the radioisotopes that can be produced with high efficiency. Another example is US9202600B2 (and CA2594829C and GB 2436508B) which illustrates the production of radionuclides using high energy accelerators and mass separation. The main problem is also to ensure the availability of radionuclides produced in high yields for their industrial application.
Technical problem
However, the methods currently used in radioisotope production have reached their limits, and new and improved methods are urgently needed to increase the availability of new and currently used isotopes. This applies in particular to the isotopic purity, yield, specific activity (specific activity) and the range of radionuclides available.
With the increasing popularity of Positron Emission Tomography (PET)/Single Photon Emission Computed Tomography (SPECT) imaging and the development of radionuclide therapy systems, there is an increasing need to prepare radioisotopes with higher radiochemistry and radionuclide purity that have not been achieved before, and to ensure proper production yields for industrial commercialization.
Furthermore, the implementation of breakthroughs in the development of drug-targeted delivery systems for new approaches to cancer treatment is limited by the lack of existing radionuclides with optimal decay characteristics for such applications. For radioligand treatment (RLT), it is necessary to ensure that the purity of the radionuclide is high enough to ensure patient safety and to minimize the risks associated with potentially harmful contaminants, both from a toxic standpoint and from a nuclear waste standpoint.
Furthermore, radionuclides can sometimes only be produced in research facilities, where radionuclide production (especially for medical applications) only accounts for a small fraction of the available time. Thus, these radionuclides cannot be used for distribution and use on a regular basis, which slows their potential use (e.g., in nuclear medicine applications and research). In view of the increasing demand for a particular radionuclide and the difficulties encountered in providing that particular radionuclide using a commercial accelerator, it is important to provide a method that makes it possible to optimize the use of the commercial accelerator, in particular during times dedicated to medical applications.
This can be achieved by using commercial accelerators and/or nuclear reactors to produce the desired radionuclide. However, sometimes the purity and specific activity of the radionuclide batches produced is not high enough for receptor targeting applications. Thus, the produced batch will require additional methods to meet these requirements, for example chemical separation may increase the purity of the batch, while mass separation may increase the purity of the radionuclide.
Summary of The Invention
The inventors have discovered a method that combines radionuclide production, chemical extraction and mass separation, providing a cost-effective, flexible and efficient method for large-scale production of various radionuclides with high purity and specific activity suitable for receptor targeting applications.
It is therefore an object of the present invention to provide a method for producing radionuclides of high purity and high specific activity. Specific activity is understood to be the ratio of the activity of the produced radionuclide to the total mass of all nuclides belonging to the same element of the produced radionuclide.
Detailed Description
In this aspect, there is provided a method of producing a radionuclide of high specific activity comprising the steps of:
a) Irradiating the target of interest with a particle beam to obtain an irradiated target comprising the radionuclide of interest,
b) Extracting the radionuclide of interest from the irradiated target chemically to increase its chemical purity,
c) The radionuclides of interest are mass separated to yield radionuclides of high specific activity.
The particle beam may be a proton, neutron, photon, deuteron, or alpha particle. As the particle beam, when considering accelerator-based production, a proton beam is preferably used; when considering reactor-based production, neutron beams are preferably used. The particle beam induces a nuclear reaction to obtain an irradiated target comprising the radionuclide of interest.
The main purpose of step b) is to increase the batch purity and to strongly increase the efficiency of step c) by eliminating a large part of the critical impurities.
Another object of the present invention is a radionuclide of high specific activity obtainable by the method of the invention.
Yet another object of the present invention is the medical use of the high specific activity radionuclides of the present invention. The present invention relates to a radionuclide of high specific activity according to the invention for use in a method of treatment of the human or animal body by therapy or in a diagnostic method performed on the human or animal body.
The radionuclides of interest are known radionuclides, with preferred known radionuclides being alpha emitters, beta (-) emitters, beta (+) emitters, gamma emitters, auger emitters. Preferred known radionuclides belong to the following radionuclides: f-18, sc-43, sc-44, sc-47, cr-51, mn-52m, fe-52, co-55, cu-61, cu-62, cu-64, ga-66, cu-67, ga-68, as-72, as-76, rb-82, Y-86, zr-89, Y-90, ru-97, tc-99m, rh-105, in-111, ag111, sn-117m, sn-121, I-123, I-124, I-131, pr-142, pr-143, tb-149, pm-151, tb-152, sm-153, tb-155, gd-157, gd-159, tb-161, er-165, dy-166, ho-166, tm-167, er-169, yb-169, tm, 172, yb-175, lu-177, re-186, re-188, au-198, au-199, pb-203, at-211, pb-212, bi-213, ac-225 and Th-229, preferably selected from Sc-43, sc-44, sc-47, tb-149, tb-152, tb-155, tb-161, lu-177, other lanthanides and Ac-225.
The present invention makes it possible to produce batches of radionuclides that are otherwise difficult to produce or cannot be produced with sufficient radionuclide purity. These radionuclides will be produced in high purity and high specific activity and are useful in a variety of applications, such as imaging and therapeutic protocols in the medical field. Radionuclides will be useful for in vivo and in vitro studies, for example, in hospitals and research centers.
The radionuclide of interest is preferably selected from among the radionuclides available for therapeutic treatment. Diagnostic imaging and therapy with different radiolabels or different doses using the same molecule or at least very similar molecules are combined in a diagnostic integration method (theranostic approach) in nuclear medicine. Copper-67, iodine-131, and lutetium-177, for example, are gamma and beta emitters, and thus these agents are useful for imaging and therapy. In addition, different isotopes of the same element, such as iodine-123 (gamma emitter) and iodine-131 (gamma and beta emitters), can also be used for diagnosis and treatment integration purposes. Examples of updates are yttrium-86/yttrium-90 or terbium isotopes (Tb): tb-152 (beta+ emitter), tb-155 (gamma emitter), tb-149 (alpha emitter) and Tb-161 (beta emitter) [ Table 1]. Furthermore, different isotopes of different chemical elements, such as radioactive lanthanoids like Lu-177 (gamma and beta emitters for therapy) and radionuclides with similar chemical properties, such as Ga-68 (beta+ emitters), can also be used for performing diagnostic integration.
TABLE 1
Preferably, the radionuclide is selected to have a high specific activity among the isotopes of terbium. In this case, the target of interest preferably comprises natural or enriched gadolinium, preferably of the metallic type, oxide or chloride, preferably irradiated with an accelerator proton beam.
In fact, the potential need for terbium isotopes in the medical industry is increasing, and current production means are not able to meet this need. For example, natural gadolinium metal or oxide may be a good balance of raw material availability and terbium radionuclide production yield. The chemical separation mainly relates to terbium and gadolinium elements, and the mass separation mainly relates to terbium nuclides.
Preferably, the selected high specific activity therapeutic radionuclide is erbium Er-169. In this case, the target of interest preferably comprises natural or enriched (Er-168) erbium, preferably of the metallic type, oxide, nitrate or chloride, preferably irradiated with neutrons in a nuclear reactor.
In fact, the medical industry potentially requires high specific activity erbium which is not available with current production means. For example, a highly Er-168 enriched nitrate or oxide may be a good target material for achieving high yield production. Chemical separation mainly involves ytterbium and erbium elements, while mass separation mainly involves erbium nuclides.
Other preferred high specific activity radionuclides may be selected from isotopes of scandium. In this case, the target of interest preferably comprises metallic titanium, more preferably natural metallic titanium which is widely available and allows for the production of scandium radionuclides in high yields.
In fact, the medical industry is increasingly demanding for scandium isotopes, which is difficult to meet by current production means. Titanium metal is a good balance between raw material availability and scandium radionuclide production yield. The chemical separation mainly involves scandium and titanium elements, and the mass separation mainly involves scandium nuclides.
The high specific activity radionuclide may also be selected from isotopes of actinium, wherein the target of interest preferably comprises natural thorium.
In fact, the medical industry is increasingly demanding for actinides, which is difficult to meet by current production means. Natural thorium is a good balance between raw material availability and actinide production yield. Chemical separation mainly involves thorium and actinides, while mass separation mainly involves actinides.
The high specific activity radionuclide may also be selected from lutetium isotopes, in which case the target of interest preferably comprises ytterbium metal.
In fact, the medical industry is increasingly demanding for lutetium isotopes, which is difficult to meet with current production practices. Ytterbium metal is a good balance between raw material availability and lutetium radionuclide production yield. Chemical separation involves mainly lutetium and ytterbium elements, while mass separation involves mainly lutetium species.
The main steps of the present invention are listed below. These steps may also be performed in a different order or repeated multiple times to ensure that a high quality product is produced.
Step a): irradiation of target
The method of producing a radionuclide of high specific activity comprises the step a) irradiating a target of interest with a particle beam, preferably a proton beam, to obtain an irradiated target comprising the radionuclide of interest. The energy in the proton beam of step a) may be between 18 and 200MeV, preferably between 30 and 70 MeV. This energy provides a significant balance between the difficulty of producing such beams and the yield of radionuclide production. Such a proton beam may be provided by a commercial ring accelerator, such as the Arronax IBA C70 ring accelerator located in south tex, france.
Step b): chemical extraction
The method of producing a radionuclide of high specific activity comprises a step b) of chemically extracting a radionuclide batch of interest from the irradiated target.
The target of interest in step b may be dissolved in an acid solution.
This dissolution produces a solution of the target material and the radionuclide, which is the input to the chemical separation process that produces the particular radionuclide. The preferred chemical separation method is chromatography.
Step b) may comprise a step of dissolving the target of interest with, for example, an acid solution, such as an acid solution comprising nitric acid (HNO 3). The resulting solution may then be passed through a resin.
Step b) may comprise liquid/liquid extraction.
Liquid/liquid extraction enables a good balance between the cost of the materials required for chemical separation and the volume of the experimental set-up (volume) for high target substance separation.
Step b) may also comprise liquid/solid extraction.
Liquid/solid extraction can be a good balance between the cost of the materials required for chemical separation and the volume of the experimental set-up for high target substance separation.
This chemical separation step provides an improvement in radiochemical purity. Thus, it enhances the efficiency of the mass separation of step c), thereby increasing the yield obtainable by the present invention by eliminating target material compared to the desired radionuclide.
According to any embodiment, the method of producing a high specific activity radionuclide may further comprise step b 2) target coupling comprising:
-pouring the liquid solution obtained in step b) onto a support (support), preferably a metal support, -heating and evaporating the liquid solution on the support in order to deposit the radionuclide on the support, -inserting the support comprising the radionuclide of interest into a mass separation system.
If gadolinium is the target of interest, step b) may comprise a step of dissolving the metallic gadolinium in an acid solution, preferably an acid solution comprising nitric acid. The resulting solution may then be passed through a resin. This step is explained in more detail in example 2.
This step may reduce the gadolinium content, which will improve the efficiency of the subsequent mass separation.
If the high specific activity radionuclide is selected from isotopes of scandium, step b) may comprise a step of dissolving the metallic titanium in an acid solution, preferably hydrobromic acid (HBr). The process may require the application of a potential difference to cause the metal to tend to dissolve, and then dissolving the resulting solution into the acid and passing it through the resin.
This step allows for a reduction of the titanium content, which will improve the efficiency of the subsequent mass separation.
Step c): mass separation
Contaminants belonging to the same element cannot be separated by chemical separation. Therefore, mass separation (mass separation) is preferable in view of the physical separation method. The mass separation step allows higher specific activity radionuclides and higher radiopurities to be obtained.
The method of producing a high specific activity radionuclide comprises the step c) of mass separating batches of the radionuclide of interest to obtain the high specific activity radionuclide, wherein the mass separation is usually performed using a target oven (target over) to evaporate atoms, using an ionizer to ionize the atoms, using extraction electrodes to post-accelerate the ions, using magnets to achieve the mass separation, and using a collection carrier (collection support).
In the mass separation step, ionization of atoms may be achieved by conventional ion sources. Finally, laser ionization can be considered to increase ionization efficiency.
Step d) second chemical separation (optional)
The method of producing a radionuclide of high specific activity may further comprise a step d) consisting of performing a second chemical separation and purification after the mass separation step.
This is an unnecessary step, which may not occur since the product extracted after mass separation is very pure. However, it does have a certain attraction as long as it is desired to find a good balance between the time required for a very good first chemical separation, then mass separation, and the final product. In these cases, the chemical separation may be divided into two steps, namely a first chemical separation before the mass separation and a second chemical separation after the mass separation. Furthermore, depending on how the radionuclides are collected after mass separation, a second purification may be required. In practice, different methods may be used for collecting radionuclides. For example, if the radionuclide is deposited on a metal plate, a second chemical separation is required to collect the generated radionuclide.
Brief Description of Drawings
Other features, details, and advantages are set forth in the following detailed description and drawings, wherein: FIG. 1
FIG. 1 is a flow chart showing radionuclides expected to be generated upon irradiation of a natural titanium target based on the energy of the irradiation beam;
FIG. 2
FIG. 2 is a flow chart showing the theoretical scandium yields achievable from different targets.
Examples
Example 1
Scandium 47 production
Preliminary description:
it is important to determine the best possible starting material (delivery material).
In scandium-47 production, natural titanium has proven to be a good balance between availability, cost and physical properties, but enriched titanium or enriched calcium may also be used. As shown in FIG. 1, sc-47 can be produced from natural titanium using a proton beam with an energy below 70 MeV. However, other contaminants may also be produced at the same time, of which the most important is the rather long life of Sc-46, which is undesirable when considering the medical application of Sc-47. That is why the appropriate purification and mass isolation steps described in the present invention are necessary in order to obtain a product that can be used in medical applications, such as radionuclides with high production yields, high purity and high specific activity.
The production yield evaluated and shown in fig. 2 should be determined.
The following table 2 lists theoretical calculations of potential contaminants produced by irradiating a natural titanium target. These calculations were performed using MCNPx software. Most of the listed contaminants can be removed by chemical separation. The main problem relates to Sc-46 which requires additional separation, e.g. mass separation. At the end of bombardment (EOB), the ratio of Sc-46 to Sc-47 yields approaches 10%, which is too high for medical applications, especially for RTL applications.
TABLE 2
Theoretical estimates may be considered, wherein one of the metallic titanium disks has a thickness of 4mm and a diameter of 26mm. The metal disc was placed in a proton beam of 70MeV and 25. Mu.A for 3 days (3 days corresponding to the half-life of Sc-47).
After irradiation, the radionuclide batch of interest is chemically separated and purified from the irradiated target. A potential difference is applied to the irradiated target to promote its dissolution in dilute HBr. Subsequently, dilute HNO is used 3 The (modification) acid solution is adjusted to meet the conditions at the resin inlet. After washing with the appropriate medium, the Sc elutes from the resin. The titanium content of the eluted solution is significantly reduced compared to the initial solution. This may reduce the amount of Ti-47, which cannot be separated during the mass separation step. This disadvantage can be overcome by laser ionization.
At this time, the specific activity per unit target mass of the method was 65.8MBq/mg.
The radionuclide batches are then separated according to a mass separation method, wherein atoms of mass 47 and the final molecules can be selectively extracted and recovered onto a dedicated foil (e.g. zinc-coated gold carrier), from which Sc-47 is chemically recovered from the foil material.
At the end of the method according to the invention, the specific activity per unit target mass is approximately 2.8x10 3 GBq/mg, near maximum theoretical specific activity, i.e. 3.08x 10 4 GBq/mg。
After mass separation, further chemical separation may be required to remove residual titanium content from the resulting radionuclide batch to further enhance radiochemical purity.
Example 2
For the production of Tb-155 (also for the other two Tb radionuclides, such as Tb-149 and Tb-152) three metal gadolinium foils (thickness 25 μm) purchased from GoodFe were used as targets. They were irradiated with 55MeV protons at 30 μa for 12 hours on an aroax annular accelerator. The latter energy is based on our target design choice to achieve 33MeV on the target. The Tb-155/Gd ratio at EOB was 1:2.7E6. The main radioactive contaminants are listed in the following table:
| radionuclides | Expected active EOB (MBq) |
| Tb-155 | 774 |
| Tb-153 | 1568 |
| Tb-156 | 328 |
| Tb-154 | 3929 |
| Gd-159 | 1076 |
After irradiation, 3 targets were detached from the target holder.
The chemistry consisted of 2 chromatography columns (column 1 (500 mm, v=36.9 mL) and column 2 (250 mm, v=8.6 mL)) packed with Ln resin. All elution was performed at 1mL/mn using a high pressure pump.
Gadolinium foil was dissolved in concentrated nitric acid (2M) and then evaporated to dryness. The dried residue was recovered into 3mL of dilute nitric acid (0.75M) and loaded into a previous wash to remove impurities and prepared (using HNO) 3 0.75M) on column 1. Under these conditions gadolinium is less retained by the column than Tb, thereby allowing a large part of it to be purified by using 40mL HNO 3 0.75M and then 80mL HNO 3 The 1M wash column was removed. Then use 45mL HNO 3 1M and subsequently 40mL HNO 3 The terbium element was eluted by 2M. Then 85mL was evaporated to dryness and dried over 3mL HNO 3 Recovered in 0.75M for a second purification step using column 2. The solution was poured onto column 2 using 12mL HNO 3 0.75M and then 15mL HNO 3 Trace amounts of gadolinium were washed away with 1M. Then 10mL HNO is used 3 1M and subsequently 15mL HNO 3 Terbium was recovered in 2M. The 25mL was then evaporated to dryness.
After cooling, the residue was recovered to 3mL of 0.01M HNO 3 Is a kind of medium. The terbium solution obtained is then poured onto tantalum boats covered with rhenium suitable for use in mass separation target systems, in particular in the CERN-MEDICIS target system, as this is considered in this example. The sample is then heated to evaporate the acid and obtain a terbium residue deposited on the rhenium carrier. Tantalum is then shipped to the CERN and inserted into the CERN-MEDICIS target for mass separation. At the end of these chemical steps, the Tb155:Gd ratio was below 1:20, a very high improvement was obtained from the EOB ratio.
The target system was installed in CERN MEDICIS and a mass separator was provided for terbium extraction. The target is heated to 600A to allow optimization of the laser on the mass 159. The laser on/off ratio of 620/110pA was measured. The target was heated to 700A and einzel was optimized at 22.3 kV. The primary current (primary current) was measured (FC 70) 726 nA. The split currents were 241pA laser on and 245pA laser off. On the sample 194pA was measured, 5.8pA on the collimator. The target was heated to 750A, resulting in a current on the sample of 600pA (3.8 pA in the collimator). The maximum current measured on the sample was 900pA (collimator 3 pA). The collection time was 22 hours.
The target loaded on the separator had an activity of 230MBq and the collected Tb-155 was 2.9MBq, corresponding to a total efficiency of 1.3% and a radioactive purity higher than 99.9%.
Further chemical purification is required to extract the Tb-155 atoms from the implanted zinc coated gold foil.
Example 3
The native Er-2O3 target was irradiated with a 72MeV proton beam to produce Tm-165, 167 and 168 radionuclides. The Target with a total activity of 150MBq was transferred to a Target and ion source unit (Target and Ion Source Unit) and coupled to a medis Target Station (Target Station). Isotope mass separation was continued for 4 days at 167 mass, 60kV beam energy, and ion source temperatures between 2100 ℃ and 2190 ℃ and the target was steadily increased from 1760 ℃ to 2300 ℃ over the 4 days. The total ion beam current is between 14nA and 8 uA. During collection at a=167, the measured beam intensity fluctuates between 53pA and 118nA, with a gaussian beam profile of sigma H1.0 mm x V0.74 mm. The separated activities were collected on 3 metal foils and distributed in the room sections. The activity of the initial Tm-167 in the target before separation was 77MBq, and after collection was completed, the activity after separation was recorded as 42MBq, which indicates that the separation efficiency was 54%. Radionuclide purity was assessed using a high purity germanium detector and found to be better than 99.99% and Tm-165 and Tm-168 contaminant activity below the detection threshold.
Conclusion(s)
These examples show that radionuclides of interest can be obtained with high specific activity, high purity and potentially high yields by means of the process of the invention. The examples also show how the chemical separation is performed prior to the mass separation to increase the efficiency of the latter, and how important the mass separation step is in order to enhance the radionuclide purity.
Claims (16)
1. A method of preparing a radionuclide of high specific activity comprising the steps of:
a) Irradiating the target of interest with a particle beam to obtain an irradiated target comprising the radionuclide of interest,
b) The radionuclide of interest is chemically extracted from the irradiated target,
c) The radionuclide batch of interest is mass separated to obtain radionuclides of high specific activity.
2. The method for preparing a radionuclide according to claim 1, wherein the particle beam of step a) is a proton beam with energy between 18 and 200 MeV.
3. The method of preparing a radionuclide of high specific activity according to claim 1 or 2, wherein step b) comprises dissolving the target of interest in an acid solution.
4. A method of preparing a high specific activity radionuclide according to any of claims 1 to 3, wherein the high specific activity radionuclide is selected from isotopes of terbium, and wherein the target of interest comprises gadolinium metal.
5. The method of preparing a high specific activity radionuclide according to claim 4, wherein step b) comprises dissolving gadolinium metal in nitric acid solution and passing the resulting solution through the resin.
6. A method of preparing a high specific activity radionuclide according to any of claims 1 to 3, wherein the high specific activity radionuclide is selected from isotopes of scandium, and wherein the target of interest comprises metallic titanium.
7. The method of preparing a high specific activity radionuclide according to claim 6, wherein step b) comprises applying a voltage to the metallic titanium while it is exposed to the HBr solution, dissolving the solution into the acid, and passing the resulting solution through the resin.
8. The method of preparing a radionuclide with high specific activity according to any of claims 1 to 7, wherein step b) comprises liquid/liquid extraction.
9. The method of preparing a radionuclide with high specific activity according to any of claims 1 to 7, wherein step b) comprises liquid/solid extraction.
10. A method of preparing a high specific activity radionuclide according to any of claims 1 to 3, wherein the high specific activity radionuclide is selected from isotopes of actinides, and wherein the target of interest comprises natural thorium.
11. A method of preparing a high specific activity radionuclide according to any of claims 1 to 3, wherein the high specific activity radionuclide is selected from isotopes of erbium, and wherein the target of interest comprises natural erbium.
12. A method of preparing a high specific activity radionuclide according to any of claims 1 to 3, wherein the high specific activity radionuclide is selected from isotopes of lutetium, and wherein the target of interest comprises ytterbium metal.
13. The method of preparing a radionuclide with high specific activity according to any of claims 1 to 12, further comprising step b 2) target coupling comprising:
pouring the liquid solution obtained in step b) onto a support, preferably a metal support,
-heating and evaporating the liquid solution on the carrier, thereby depositing the radionuclide on the carrier, -inserting the carrier containing the radionuclide of interest into the mass separator.
14. The method for preparing a radionuclide with high specific activity according to any of claims 1 to 13, further comprising step d 2) a second chemical separation and purification after the mass separation step.
15. A high specific activity radionuclide obtainable by the method of any one of claims 1 to 14.
16. The high specific activity radionuclide according to claim 15, for use in a method of treating the human or animal body by therapy or in a diagnostic method carried out on the human or animal body.
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