METHOD FOR PRODUCING HIGH PURITY AND HIGH SPECIFIC ACTIVITY RADIONUCLIDES

Abstract

The invention relates to a method for producing high specific activity radionuclides, comprising the steps of: a) irradiating a target of interest by a particle beam, so as to obtain an irradiated target comprising radionuclides of interest, b) chemically extracting a batch of radionuclides of interest from the irradiated target, c) mass-separating the batch of radionuclides of interest so as to obtain high specific activity radionuclides.

Claims

1-16. (canceled)

17. Method for producing high specific activity radionuclides, comprising the steps of: a) irradiating a target of interest by a particle beam, so as to obtain an irradiated target comprising radionuclides of interest, b) chemically extracting the radionuclides of interest from the irradiated target c) mass-separating the batch of radionuclides of interest so as to obtain high specific activity radionuclides.

18. Method for producing high specific activity radionuclides according to claim 17, wherein the particle beam of step a) is a proton beam presenting an energy comprised between 18 and 200 MeV.

19. Method for producing high specific activity radionuclides according to claim 17, wherein step b) comprises dissolving the target of interest into an acid solution.

20. Method for producing high specific activity radionuclides according to claim 17, wherein the high specific activity radionuclides are chosen among the isotopes of terbium, and wherein the target of interest comprises metallic gadolinium.

21. Method for producing high specific activity radionuclides according to claim 20, wherein step b) comprises dissolving metallic gadolinium within a nitric acid solution and passing the obtained solution through a resin.

22. Method for producing high specific activity radionuclides according to claim 17, wherein the high specific activity radionuclides are chosen among the isotopes of scandium, and wherein the target of interest comprises metallic titanium.

23. Method for producing high specific activity radionuclides according to claim 22, wherein step b) comprises exposing metallic titanium to an HBr solution while submitting it to a voltage, dissolving the solution into an acid and passing the obtained solution through a resin.

24. Method for producing high specific activity radionuclides according to claim 17, wherein step b) comprises a liquid/liquid extraction.

25. Method for producing high specific activity radionuclides according to claim 1, wherein step b) comprises a liquid/solid extraction.

26. Method for producing high specific activity radionuclides according to claim 17, wherein the high specific activity radionuclides are chosen among the isotopes of actinium, and wherein the target of interest comprises natural thorium.

27. Method for producing high specific activity radionuclides according to claim 17, wherein the high specific activity radionuclides are chosen among the isotopes of erbium, and wherein the target of interest comprises natural erbium.

28. Method for producing high specific activity radionuclides according to claim 17, wherein the high specific activity radionuclides are chosen among the isotopes of lutetium, and wherein the target of interest comprises metallic ytterbium.

29. Method for producing high specific activity radionuclides according to claim 17, further comprising a step b2) of target coupling comprising: pouring a liquid solution obtained in step b) on a support, heating up and evaporating the liquid solution on the support so as to deposit the radionuclide on the support, inserting the support comprising the radionuclides of interest into a mass separator.

30. Method for producing high specific activity radionuclides according to claim 17, further comprising a step d2) of a second chemical separation and purification after the mass separating step.

31. High specific activity radionuclides obtainable by a method according to claim 17.

32. A method for treating or diagnosing a human or animal body comprising administering a high specific activity radionuclide according to claim 31 to said human or animal body in need thereof.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0061] Other features, details and advantages will be shown in the following detailed description and on the figures, on which:

FIG. 1

[0062] FIG. 1 is a flowchart representing the radionuclides which are expected to be generated upon irradiating a natural titanium target, depending on the energy of the irradiating beam;

FIG. 2

[0063] FIG. 2 is a flowchart representing the theoretical scandium yield achievable starting from different targets.

EXAMPLES

Example 1

[0064] Scandium 47 Production

[0065] Preliminary Remarks:

[0066] It is of utter importance to determine the best possible departing material.

[0067] In case of Scandium-47 production, natural titanium proves to be a good compromise between availability, cost and physical properties, in alternative enriched titanium or enriched calcium can be used too. As shown on FIG. 1, production of Sc-47 out of natural titanium is possible with proton beam energies below 70 MeV. However, other contaminants are co-produced, most importantly the quite long-lived Sc-46 which is not desired when considering Sc-47 for medical applications. This is why appropriate purification and mass separation steps as described in the present invention are mandatory in order to obtain a product usable for medical application e.g. high production yields, high-purity and high specific activity radionuclides.

[0068] One should determine the production yield evaluated and shown on FIG. 2.

[0069] Table 2 below lists the theoretical calculation of the potential contaminants produced by the irradiation of a natural titanium target. The calculations have been performed with the software MCNPx. Most of the listed contaminants can be removed thanks to chemical separation. Main concern regards Sc-46 which will need complementary separation, for example mass separation. The yield ratio of Sc-46 over Sc-47 is almost 10% at end of bombardment (EOB), which is too high for medical applications, in particular for the RTL applications.

TABLE-US-00002 TABLE 2 Yield EOB Yield EOB ELEMENT Half-life (Bq/A/h/g) ELEMENT Half-life (Bq/A/h/g) S-35 87 d 2.06E+03 K-38 7.6 m 2.50E+06 Cl-36 3E5 y 2.79E02 K-42 12 h 1.25E+08 Cl-39 56 m 6.25E+05 K-43 22 h 1.67E+07 Ar-37 35 d 2.72E+05 K-44 22 m 3.13E+06 Ar-39 269 y 1.73E+02 Ca-41 9.9E4 y 7.92E+00 Ar-42 33 y 1.50E+01 Ca-45 162 d 1.47E+06 Ca-47 4.5 d 8.88E+05 Sc-48 43.7 h 8.77E+07 Sc-43 3.89 h 8.10E+08 Sc-49 57 m 2.14E+08 Sc-44 3.97 h 9.66E+09 Ti-44 60 y 1.97E+04 Sc-45m 318 ms 2.78E+01 Ti-45 185 m 6.81E+09 Sc-46 83.8 d 5.48E+07 V-47 32 m 3.22E+09 Sc-47 3.34 d 5.29E+08 V-48 16 d 8.66E+07

[0070] Theoretical estimation can be performed considering one metallic titanium disk having a thickness of 4 mm and a diameter of 26 mm. The metallic disk is submitted to a 70 MeV and 25 A proton beam for 3 days (3 days corresponds to the Sc-47 half-life).

[0071] After the irradiation, a batch of radionuclides of interest is chemically separated and purified from the irradiated target. A differential of potential is applied to the irradiated target to favor the dissolution of the latter in diluted HBr. After that, the acid solution is modified with diluted HNO.sub.3 in order to satisfy the conditions at the entry of the resin. After washing with the appropriate media, the Sc is eluted from the resin. The eluted solution will have a strongly reduced titanium content compared to the initial solution. This allows reducing the high amount of Ti-47 which cannot be separated during the mass separation step. This drawback may be overcome using laser ionization.

[0072] The specific activity per unit target mass is at this point of the process 65,8 MBq/mg.

[0073] Then, the batch of radionuclides is separated according to a mass separation process, wherein the atoms and eventually molecules having mass 47 can be selectively extracted and recovered on a dedicated foils, as for example a Zn coated gold support, which undergo chemical process to recover Sc-47 from the material of the foil.

[0074] The specific activity per unit target mass is at end of the process according to the invention around 2,810.sup.3 GBq/mg close to the maximum theoretical specific activity which is 3,0810.sup.4 GBq/mg.

[0075] A further chemical separation might be foreseen after the mass separation to remove the residual titanium content from the produced radionuclide batch in order to further increase the radiochemical purity.

Example 2

[0076] For the Tb-155 production (this applies also for the two other Tb radionuclides, such as Tb-149 and Tb-152), three metallic gadolinium foils (25 m thick) purchased from Goodfellow were used as targets. They were irradiated at the Arronax cyclotron for 12 h at 30 A using protons of 55 MeV. This latter energy is chosen to get 33 MeV on target based on our target design). The Tb-155/Gd ratio at EOB was 1:2.7E6. The main radioactive contaminants are presented in the table below:

TABLE-US-00003 Expected activity EOB Radionuclide (MBq) Tb-155 774 Tb-153 1568 Tb-156 328 Tb-154 3929 Gd-159 1076
After irradiation, the 3 targets are dismounted from the target holder.

[0077] The chemical process is made of 2 chromatographic columns filled of Ln resin (column 1 (500 mm, V=36.9 mL) and column 2 (250 mm, V=8.6 mL)). All elutions are made at 1 mL/mn using a high-pressure pump.

[0078] The Gd foils are dissolved in concentrated nitric acid (2 M) and then evaporated to dryness. The dry residue was recovered in 3 mL of diluted nitric acid (0.75 M) and loaded onto column 1 previously washed to remove impurities and prepared with HNO.sub.3 0.75 M. In these conditions, gadolinium is less restrained by the column than Tb allowing to remove a large part of it by washing the column using 40 mL of HNO.sub.3 followed by 80 mL of HNO.sub.3 1.M. The terbium element was then eluted using 45 mL of HNO.sub.3 1 M followed by 40 mL of HNO.sub.3 2 M. The 85 mL are then evaporated to dryness and recovered in 3 mL HNO.sub.3 0.75 M for a second purification step using column 2. The solution is poured on column 2, traces of Gd are eluted using 12 mL HNO.sub.3 0.75 M followed by 15 mL of HNO.sub.3 1.M. Tb is then recovered using 10 mL of HNO.sub.3 1.M followed by 15 mL of HNO.sub.3 2 M. These 25 mL are evaporated to dryness.

[0079] After cooling, the residue is recovered in 3 mL of 0.01 M HNO.sub.3. The obtained terbium solution was then poured onto a tantalum boat covered with rhenium suitable for the mass separation target system, in particular to the CERN-MEDICIS target system as it was the one considered in this example. Then the sample was heated up to evaporate the acid and obtain the terbium residue deposited on the rhenium support. The tantalum boat is then shipped to CERN and inserted in CERN-MEDICIS target for mass separation. At the end of the these chemical steps, the ratio Tb155:Gd is below 1:20, very high improvement from EOB ratio.

[0080] The target system was installed at CERN MEDICIS, and the mass separator was setup for the terbium extraction. The target has been heated up to 600 A to allow optimization of the laser on mass 159. A laser on/off ratio of 620/110 pA has been measured. The target has been heated up to 700 A and the einzel optimised at 22.3 kV. A primary current of (FC70) 726 nA has been measured. The separated current was 241 pA laser on and 245 pA laser off. On the sample, 194 pA were measured with 5.8 pA on the collimator. The target has been heated to 750 A, giving a current on the sample of 600 pA (3.8 pA on the collimator). The maximum current measured on the sample was 900 pA (collimator 3 pA). The collection time was of 22 hours.

[0081] The target loaded on the separator had an activity of 230 MBq and the collected Tb-155 was 2.9 MBq corresponding to an overall efficiency of 1.3% with a radionuclidic purity higher than 99.9%

[0082] A further chemical purification is needed to extract the Tb-155 atoms from the implantation zinc-coated gold foil.

Example 3

[0083] A natural Er-203 target was irradiated with a proton beam of 72 MeV to produce Tm-165, 167 and 168 radionuclides. The target with a total of 150 MBq activity was transferred in a Target and Ion Source Unit and coupled to the MEDICIS Target Station; the isotope mass separation took place over 4 days at mass 167, at a beam energy of 60 kV with a ion source temperature between 2100 and 2190 C., and a target that was steadily increased over the 4 days from 1760 C. to 2300 C. The total ion beam current was comprised between 14 nA and 8uA. The measured beam intensity during collection at A=167 varied between 53 pA and 118 nA, with a gaussian beam profile of sigma H1.0 mmV0.74 mm. The separated activity was collected over 3 metallic foils and distributed partly in the chamber. The starting Tm-167 activity in the target before separation was 77 MBq, and the recorded separated activity of 42 MBq at End of Collection; this provides a separation efficiency of 54%. The radionuclidic purity was assessed by high purity Germanium detector and found to be better than 99.99%, with Tm-165 and Tm-168 contaminants activities below the detection threshold.

CONCLUSION

[0084] It has been shown in these examples that radionuclide of interest with high specific activity, high purity and potentially high yields can be obtained thanks to the method of the invention. The example also shows how the chemical separation before mass separation improves the efficiency of the latter, and how the mass separation step is important in order to enhance radionuclidic purity.