JP6534581B2 - Method for producing radioactive gallium, method for producing medicament containing the radioactive gallium, method for recovering zinc stable isotope - Google Patents

Description

  The present invention relates to a method of producing radioactive gallium.

Radioactive gallium such as ⁶⁷ Ga and ⁶⁸ Ga is often used as a radionuclide in nuclear medicine examination, for example, ⁶⁷ Ga is produced by (p, 2n) nuclear reaction of ⁶⁸ Zn using an accelerator. Since natural zinc has isotopes such as ⁶⁴ Zn, ⁶⁶ Zn, ⁶⁷ Zn, ⁶⁸ Zn, and ⁷⁰ Zn, the ⁶⁸ Zn target can not be obtained unless it is highly enriched from natural zinc. Therefore, after the production of ⁶⁷ Ga, and recovered ⁶⁸ Zn, be reused in the production of ⁶⁷ Ga is conventional.

^As a method of recovering ⁶⁸ Zn, conventionally, after dissolving ⁶⁸ Zn using sodium cyanide using a method using an ion exchange resin (Non-patent Documents 1 and 2), add sodium sulfide to the filtrate, and ⁶⁸ A method of precipitating and recovering Zn (Non-patent Document 3) and the like are known.

International Journal of Applied Radiation and Isotopes, (1973) vol. 24, pp. 651-655 Proceedings of the Fifth International Workshop on Targetry and Target Chemistry (1993) Session II, Targetry and Production, pp. 121-126 Nuclear Instruments and Methods in Physics Research, A282 (1989) pp. 296-300

  However, the method using an ion exchange resin such as non-patent documents 1 and 2 is a radioactive foreign metal produced by the resin produced in the recovery operation originating from the target material and the member for holding it in the vacuum box. It becomes a problem in terms of disposal because it is polluted. In addition, when a large amount of zinc is recovered, the amount of resin used is large, and the problem of disposal becomes significant.

  In the method using sodium cyanide as in Non-patent Document 3, zinc to be recovered is precipitated, and the above-mentioned foreign metal is dissolved in cyan waste liquid. This waste liquid is contaminated with radioactive foreign metals, and since cyanide is a toxic substance, there is a problem that it can not be discarded unless its activity is attenuated or the cyanide is detoxified.

  An object of the present invention is to recover zinc stable isotope purified to a quality that does not affect the production efficiency of radioactive gallium while reducing the amount of radioactive foreign metal-contaminated waste.

  As a result of intensive studies to solve the above problems, the present inventors have deposited and removed foreign metals, thereby reducing radioactive wastes contaminated with foreign metals and reducing the production efficiency of radioactive gallium. It has been found that it is possible to recover zinc stable isotope purified to a quality that does not affect the present invention, and the present invention has been completed.

  That is, one aspect of the present invention is a method for producing radioactive gallium by irradiating accelerated particles with an zinc stable isotope from an accelerator, wherein the zinc stable isotopes are electrodeposited on a copper plate and irradiated with accelerated particles. Purification step including a first step of removing the first precipitate generated by passing hydrogen sulfide through an acidic solution containing the substance, and a nucleus for producing radioactive gallium from the zinc stable isotope recovered through the purification step And providing a process for producing radioactive gallium.

  Another aspect of the present invention is a method of producing a medicament containing radioactive gallium as an active ingredient, which comprises the steps of producing radioactive gallium using the above method, and formulating the radioactive gallium. And providing a method for producing a medicament.

  In addition, another aspect of the present invention is a method of recovering zinc stable isotope after producing radioactive gallium by irradiating accelerated particles from an accelerator to zinc stable isotope electrodeposited on a copper plate, The present invention provides a method including the step of purifying zinc stable isotopes by removing precipitates generated through hydrogen sulfide in an acidic solution containing zinc stable isotopes after irradiation of particles.

  According to the present invention, since hydrogen sulfide is caused to act on the zinc stable isotope electrodeposited on the copper plate and the accelerated particles are irradiated, it is derived from the target material and the member for holding it in the vacuum box. Because foreign metals can be precipitated as sulfides, stable isotopes of purified zinc are recovered to a quality that does not affect the production efficiency of radioactive gallium while reducing radioactive foreign metal-contaminated wastes. can do.

  The method of producing radioactive gallium of the present invention is to generate radioactive gallium by nuclear reaction by irradiating accelerated particles from an accelerator to zinc stable isotope electrodeposited on a copper plate.

  The zinc stable isotope can be electrodeposited on a copper plate according to a known method, and specifically, the zinc stable isotope is electrodeposited on the copper plate by energizing a solution of the zinc stable isotope. The solution of zinc stable isotope only needs to be capable of dissolving zinc stable isotope as an ion, and can be prepared, for example, by dissolving zinc oxide or zinc hydroxide in an aqueous solution of sodium hydroxide. Also, as described later, the zinc stable isotope can be electrodeposited on a copper plate using a solution of zinc stable isotope recovered by the method of the present invention.

Preferably, the radioactive gallium is ⁶⁷ Ga and the zinc stable isotope is ⁶⁸ Zn. The ⁶⁸ Zn electrodeposited on a copper plate is irradiated with a proton beam from a cyclotron to generate ⁶⁷ Ga by a ⁶⁸ Zn (p, 2n) ⁶⁷ Ga reaction.

  After the formation of radioactive gallium, the electrodeposited zinc stable isotope and the generated radioactive gallium can be dissolved in the liquid acidic substance, but at this time, the target substance or the substance for holding it in a vacuum box can be dissolved. The foreign metals derived from the components are also eluted concomitantly. Radioactive gallium can be separated from zinc stable isotopes and foreign metals by extraction into an organic phase by adding an organic solvent such as diisopropyl ether (gallium separation step). Copper, iron, aluminum etc. are mentioned as a dissimilar metal. Copper is derived from a copper plate. Other dissimilar metals are derived from the material which comprises the holder used for fixing a copper plate.

  As the liquid acidic substance to be used for dissolving the above zinc stable isotope etc., one capable of dissolving zinc stable isotope as ion is preferable. Specifically, an acidic aqueous solution such as hydrochloric acid or nitric acid can be used, and hydrochloric acid It is more preferable to use As a result, since metals such as silver and lead precipitate, it is possible to separate zinc stable isotope dissolved in hydrochloric acid and radioactive gallium dissolved in an organic solvent from radioactive foreign metals such as silver and lead.

  The residue after separation of radioactive gallium may contain copper, iron, and aluminum as foreign metals in addition to zinc stable isotopes. Therefore, by removing these foreign metals, zinc stable isotopes of higher purity can be recovered.

  For this reason, according to the invention, the purification step of the invention is carried out in order to remove these foreign metals. Specifically, the purification step is carried out by leaving the residue after separating radioactive gallium as it is or concentrating it, and acting hydrogen sulfide under an acidic solution. More specifically, since the zinc stable isotope after irradiation is dissolved in the liquid acidic substance, hydrogen sulfide can be passed through the acidic solution containing this zinc stable isotope as it is, or the acidic solution can be concentrated. Alternatively, after adding a liquid acidic substance such as hydrochloric acid or nitric acid to the acid solution, hydrogen sulfide can be passed through the acid solution to carry out the action of hydrogen sulfide under the acid solution. Thereby, for example, copper can be precipitated as copper sulfide. In the present invention, the zinc stable isotope can be purified by removing these sulfides as a first precipitate by a solid-liquid separation method such as filtration or centrifugation (the first step of the purification step). .

  In the present invention, the residue after separating radioactive gallium is preferably a hydrochloric acid solution. Hydrogen sulfide can be generated by a known method, for example, can be generated by mixing iron sulfide and hydrochloric acid, and it can be mentioned that the solution is vented. When using hydrogen sulfide, it is preferable to take safety measures such as installing an anemometer in a draft or installing an alarm. Whether copper could be separated from the zinc stable isotope by the solid-liquid separation method is visually evaluated whether the color of the solution after removal of the first precipitate is colorless and transparent because copper sulfide has a black color. It can be determined by observing. After removing the precipitate, the zinc stable isotope can be recovered by evaporating the hydrochloric acid by heating.

  Alternatively, ammonia may be added to the solution after the first precipitate has been removed, and the resulting precipitate (second precipitate) may be removed by a solid-liquid separation method such as filtration, centrifugation (purification Second step of the process). In this way, foreign metals such as iron and aluminum can be removed as precipitates. The second step of the purification step may be performed when the solution of zinc stable isotope obtained in the first step contains iron in an amount of more than 5 ppm. The content of iron can be measured according to a known method, but may be determined by comparison with the color of a 5 μg / mL iron standard solution using, for example, a color reaction with potassium thiocyanate.

  In the second step, preferably, nitric acid and aqueous ammonia are added to the solution after removing the first precipitate. After removing the precipitate, the nitric acid and the ammonia water are evaporated by heating. In this way, stable zinc isotopes can be recovered.

  The stable zinc isotope recovered through the purification step including the first step and the second step as needed is removed as a source of radioactive gallium by removing the solvent by heating evaporation or the like and concentrating it. It can be used and can be subjected to a nuclear reaction step of producing radioactive gallium. Preferably, the purified zinc stable isotope is dissolved in an acidic aqueous solution such as sulfuric acid to form an electrolytic solution, and this is energized to cause electrodeposition on a copper plate to form an electrodeposited layer of zinc stable isotope on the surface of the copper plate. (Electro-deposition step). Thus, unlike the conventional electrodeposition method, the electrodeposition operation can be performed more safely because toxic sodium cyanide is not used.

  In the above-mentioned nuclear reaction process, radioactive gallium can be produced by irradiating accelerated particles from the accelerator to the recycled zinc stable isotope. The zinc stable isotope by-produced by the method of producing the radioactive gallium of the present invention may be further subjected to the purification step and the nuclear reaction step of the present invention, and repeatedly executing this repeatedly wastes the zinc stable isotope waste. It can be effectively used as a raw material for radioactive gallium production without The obtained radioactive gallium is diluted to an appropriate concentration with water or physiological saline, and subjected to a formulation process such as sterilization (formulation process), and is also used as a drug containing the same as an active ingredient. Good. For example, it can be used for nuclear medicine diagnosis as a tumor imaging agent by using citric acid as a counter ion as radioactive gallium citrate and formulating it.

  Hereinafter, the present invention will be more specifically described by way of examples, but the present invention is not limited to only the following examples.

Example 1
A ⁶⁸ Zn target electrodeposited on a copper plate was irradiated with a proton beam using a cyclotron (product name: Cyclone 30, manufactured by IBA) to generate ⁶⁷ Ga by a ⁶⁸ Zn (p, 2n) ⁶⁷ Ga reaction. ^{The 68} Zn target was dissolved in iron-free hydrochloric acid, ⁶⁷ Ga was extracted using diisopropyl ether, and the residue ⁶⁸ Zn hydrochloric acid solution was concentrated by heat evaporation. After cooling to room temperature, iron sulfide and 6 mol / L hydrochloric acid were mixed to generate hydrogen sulfide gas, which was then introduced into a ⁶⁸ Zn hydrochloric acid solution until the reaction disappeared. After completion of the reaction, iron sulfide and 6 mol / L hydrochloric acid were separated to stop the generation of hydrogen sulfide gas, filtered through a folded filter paper, and the filtrate was boiled on a hot plate to remove hydrogen sulfide. 2 mol / L sulfuric acid was added, and heat evaporation was performed to remove hydrochloric acid. Water for injection was added to the obtained concentrated ⁶⁸ Zn, which was electrodeposited on a copper plate as an electrodeposition solution, and was irradiated with a proton beam with the above-mentioned cyclotron to generate ⁶⁷ Ga.

Comparative Example 1
A ⁶⁸ Zn target electrodeposited on a copper plate was irradiated with a proton beam using a cyclotron (same as Example 1) to generate ⁶⁷ Ga by a ⁶⁸ Zn (p, 2n) ⁶⁷ Ga reaction. ^{The 68} Zn target was dissolved in iron-free hydrochloric acid, ⁶⁷ Ga was extracted using diisopropyl ether, and sodium hydroxide and sodium cyanide were added to the ⁶⁸ Zn hydrochloric acid solution of the residue. Sodium sulfide was then added and the resulting precipitate was centrifuged and dissolved in concentrated hydrochloric acid. After heating and concentration, sodium hydroxide is added to the obtained concentrated ⁶⁸ Zn to form a precipitate, and the precipitate is dissolved with sodium cyanide and electrodeposited on a copper plate as an electrodeposition solution, and protons are generated by the above-mentioned cyclotron. The line was irradiated to produce ⁶⁷ Ga.

[Evaluation of irradiation efficiency]
The theoretical yield of ⁶⁷ Ga was evaluated from proton range and energy loss in a ⁶⁸ Zn target and Thick-Target Yield, which were evaluated by the calculation code SRIM (The Stopping and Range of Ions in Matter).
Also, the actual yield of ⁶⁷ Ga was calculated according to the following equation.

Actual yield (MBq / μAh) = (A (MBq) × λ (h ⁻¹ ) × t (h)) / (I (μA) × t (h) × (1−exp (−λ (h ⁻¹ )) X t (h))
During the ceremony
A: ⁶⁷ Ga activity at the end of proton beam irradiation,
λ: ⁶⁷ Ga decay constant,
t: Irradiation time,
I: Average irradiation current value.

  The theoretical yield and actual yield of Example 1 and Comparative Example 1 are shown in Table 1. Table 1 shows the actual yield relative to the theoretical yield as the irradiation efficiency. As shown in Table 1, almost no difference in irradiation efficiency was observed between Example 1 and Comparative Example 1.

Example 2
^{The same} procedure as Example 1 was carried out until the hydrogen sulfide was removed from the ⁶⁸ Zn hydrochloric acid solution by boiling. Hydrochloric acid, hydrogen peroxide test solution and potassium thiocyanate test solution were respectively added to the same amount of 5 μg / mL iron standard solution and to a partially extracted ⁶⁸ Zn hydrochloric acid solution, and the coloration was compared. Nitric acid and aqueous ammonia were added to the ⁶⁸ Zn hydrochloric acid solution, which is colored in a color deeper than that of the 5 μg / mL iron standard solution, and after confirming the formation of a red precipitate (iron hydroxide), the red precipitate was removed by filtration. To the filtrate was added 2 mol / L sulfuric acid, and the solution was evaporated by heating to remove hydrochloric acid. Water for injection was added to the obtained concentrated ⁶⁸ Zn, which was electrodeposited on a copper plate as an electrodeposition solution, and was irradiated with a proton beam at the cyclotron shown in Example 1 to produce ⁶⁷ Ga.

  When the irradiation efficiency was evaluated in the same manner as in Example 1, results equivalent to those in Example 1 were obtained.

  As mentioned above, the result of the Example showed that the method of this invention was a thing which does not reduce the manufacturing efficiency of radioactive gallium compared with the conventional method.

Claims (13)

A method for producing radioactive gallium by irradiating accelerated particles from an accelerator to a zinc stable isotope,
A purification step including a first step of removing the first precipitate formed through hydrogen sulfide into an acidic solution containing said zinc stable isotope after electrodeposition on a copper plate and irradiation of accelerated particles.
A nuclear reaction step of producing radioactive gallium from the zinc stable isotope recovered through the purification step;
Of producing radioactive gallium. The method further includes an electrodeposition step of electrodepositing the zinc stable isotope recovered through the purification step on a copper plate,
The method for producing radioactive gallium according to claim 1, wherein the nuclear reaction step comprises producing radioactive gallium by irradiating the accelerated particles with the copper plate on which the zinc stable isotope is electrodeposited. The method for producing radioactive gallium according to claim 2, wherein in the electrodeposition step, an acidic solution containing the zinc stable isotope recovered through the purification step is electrodeposited on the copper plate as an electrolytic solution. The method for producing radioactive gallium according to any one of claims 1 to 3, wherein in the first step of the purification step, the first precipitate is removed by filtration. The method further includes a gallium separation step of dissolving the zinc stable isotope after electrodeposition on a copper plate and irradiation of accelerated particles in an acid solution and separating radioactive gallium using an organic solvent,
The method for producing radioactive gallium according to any one of claims 1 to 4, wherein the purification step is performed after the gallium separation step. The method according to any one of claims 1 to 5, wherein the purification step further includes a second step of removing a second precipitate formed by adding ammonia to the acidic solution from which the first precipitate has been removed. A method of producing radioactive gallium according to one aspect. The method for producing radioactive gallium according to any one of claims 1 to 6, wherein the purification step is repeatedly performed after the nuclear reaction step. The method for producing radioactive gallium according to any one of claims 1 to 7, wherein the zinc stable isotope is ⁶⁸ Zn and the radioactive gallium is ⁶⁷ Ga. A method for producing a medicament comprising radioactive gallium as an active ingredient, which comprises
A process for producing radioactive gallium using the method according to any one of claims 1 to 8;
Formulating the radioactive gallium;
A method of manufacturing a medicament, including: 10. A method of producing a medicament according to claim 9, wherein the step of formulating the radioactive gallium comprises preparing radioactive gallium citrate. A method for recovering zinc stable isotope after producing radioactive gallium by irradiating accelerated particles from an accelerator to zinc stable isotope electrodeposited on a copper plate, comprising the zinc stable isotope after irradiation of the accelerated particles Purifying the zinc stable isotope by removing the formed precipitate through hydrogen sulfide into an acidic solution containing the product. The method according to claim 11, further comprising the step of recovering purified zinc stable isotope by adding ammonia to the acidic solution from which the precipitate has been removed and removing the generated precipitate. . The method according to claim 11 or 12, further comprising the step of electrodepositing the purified zinc stable isotope on a copper plate.