Method for producing astatine solution

Abstract

The purpose of the present invention is to provide a method for producing an astatine solution with an improved recovery rate. Provided is a method for producing an astatine-211 solution, the method comprising: a step of irradiating bismuth with α rays to generate astatine-211 in the bismuth; and a step of distilling the bismuth irradiated with the α rays, separating and purifying the astatine-211, and dissolving the purified astatine-211 in a sodium hydrogen carbonate aqueous solution.

Description

How to prepare astatine solution

[0001] The present invention relates to a method for producing an astatine solution with improved recovery.

[0002] Astatine-211 ( ２１１ α-rays are alpha-ray emitting nuclides that belong to the same halogen group as iodine. Because α-rays deliver a large amount of energy over a short range, equivalent to the size of a few cells, they are expected to selectively accumulate in lesions such as cancer cells, minimizing the impact on surrounding tissues and achieving a significant therapeutic effect. In recent years, ２１１ Nuclear medicine treatment using At has been attracting attention, and sodium astatine ([ ２１１ It has been disclosed that sodium iodide [NaAt] is taken up into cancer cells via the sodium-iodide symporter, which is expressed in differentiated thyroid cancer cells, just like iodine, and that it exerts a dose-dependent inhibitory effect on tumor growth and improves survival rates (Non-Patent Documents 1 and 2, Patent Document 1). ２１１ At is formed by using bismuth (Bi) as a target material. ２０９ Bi ( ４ He, 2n) ２１１ It is produced by the nuclear reaction of At, ２１１ It is obtained in the form of a Bi plate containing At. ２１１ Dry distillation is known as a method for separating and purifying At (for example, Patent Document 1 and Patent Document 2). ２１１ At and ２０９ This is a separation technology that utilizes the difference in boiling point of Bi. By heating the electric furnace equipped with Bi plates to about 850°C, ２１１ Only At (boiling point around 330°C) is vaporized and captured in a cooling trap tube installed downstream of the electric furnace. ２１１ A good recovery rate of At has been achieved mainly by using chloroform (Non-Patent Document 3). After recovery, At is removed and reacted with a precursor having a leaving group such as a tributyltin group in an appropriate organic solvent and oxidizing agent to synthesize astatine-labeled drugs. However, chloroform is highly toxic, and its use in the manufacturing process of drugs to be administered intravenously to humans was considered to be a major problem. On the other hand, the trapped At is removed and reacted with a precursor having a leaving group such as a tributyltin group in an appropriate organic solvent and oxidizing agent to synthesize astatine-labeled drugs. ２１１It has already been reported that At is recovered with water and shows a good labeling reaction with a precursor having boronic acid as a leaving group in an aqueous solution in the presence of sodium bicarbonate and potassium iodide (Non-Patent Document 4). ２１１ The recovery rate of At was not as high as that of chloroform, and was about 30% with 0.5 mL of water (see Comparative Example 1 in Test Example 1 described later). To obtain a high yield of radioactivity in the labeling reaction using a boronic acid precursor, it was necessary to improve the recovery rate.

[0003] WO2019 / 131998WO2019 / 112034

[0004] Watabe et al., J Nucl Med 2019, volume 60, issue 9, pages 1301-1307; doi.10.2967 / jnumed.118.222638Watabe et al., Int J Mol Sci 2022, volume 23, issue 16, 9434; doi.org / 10.3390 / ijms23169434Lindegren et al., Applied Radiation and Isotopes, volume 55, issue 2, 2001, pages. 157-160Shirakami et al., Scientific Reports volume 11, Article number: 12982, 2021; doi.org / 10.1038 / s41598-021-92476-6

[0005] An object of the present invention is to provide a method for producing an astatine solution with improved recovery.

[0006] The present inventors have conducted extensive research and have found that the isolated and purified ２１１ When At is collected from the trap tube, a sodium bicarbonate solution is used. ２１１ Furthermore, the present inventors have found that the recovery rate of At can be improved. ２１１ When recovering At from the trap tube, the flow of the sodium bicarbonate aqueous solution is stopped in the trap tube for a certain period of time, and the At is recovered after being left to stand (i.e., the separated and purified At is recovered).２１１ By increasing the contact time between At and the aqueous sodium bicarbonate solution, ２１１ Based on this new finding, the present inventors have further conducted intensive studies and have completed the present invention.

[0007] That is, the present invention provides the following: [1] A method for producing an astatine-211 solution, comprising the steps of irradiating bismuth with α-rays to produce astatine-211 in the bismuth, and distilling the α-ray irradiated bismuth to separate and purify the astatine-211, and dissolving it in an aqueous sodium bicarbonate solution (also referred to as the production method of the present invention in this specification). [2] The production method according to [1] above, wherein the aqueous sodium bicarbonate solution does not contain either a reducing agent or an oxidizing agent, or both. [3] The production method according to [1] above, wherein the separated and purified astatine-211 is dissolved by contacting it with an aqueous sodium bicarbonate solution for 10 seconds or more. [4] A carrier gas used in the distillation is a mixture of an inert gas and O ２ [5] The manufacturing method according to the above [1], wherein the carrier gas further contains H ２ [6] A method for recovering astatine-211, comprising the steps of: irradiating bismuth with α-rays to produce astatine-211 in the bismuth; and distilling the α-ray irradiated bismuth to separate and purify astatine-211, and dissolving the astatine-211 in an aqueous sodium bicarbonate solution. [7] A method for recovering astatine-211, comprising the steps of: distilling the α-ray irradiated bismuth to separate and purify astatine-211; and dissolving the astatine-211 in an aqueous sodium bicarbonate solution. [8] A method for recovering astatine-211, comprising the steps of: contacting the separated and purified astatine-211 with an aqueous sodium bicarbonate solution for 10 seconds or more to dissolve the astatine-211. [9] A method for recovering astatine-211, comprising the steps of: contacting the separated and purified astatine-211 with an aqueous sodium bicarbonate solution for 10 seconds or more to dissolve the astatine-211.

[10] A method for recovering astatine-211, comprising the steps of: ２

[10] The method for recovering the oxidized carbon dioxide according to the above [6], wherein the carrier gas further contains H ２ The method for recovering hydroxybenzoates according to the above [9], wherein the hydroxybenzoates contain hydroxybenzoates.

[0008] According to the production method of the present invention, ２１１The production method of the present invention can be carried out without using highly toxic organic solvents such as chloroform and methanol. ２１１ The At solution does not require a step of distilling off the organic solvent and can be widely used in astatination reactions in aqueous solution, including labeling reactions using boronic acid precursors or tributyltin group-modified precursors. ２１１ The At solution does not contain organic solvents such as chloroform or methanol, and is therefore useful as a pharmaceutical raw material. Furthermore, the production method of the present invention can be carried out without using a reducing agent or an oxidizing agent. Therefore, the At solution obtained by the production method of the present invention is ２１１ The At solution does not contain a reducing agent or an oxidizing agent and can therefore be used in any labeling reaction.

[0009] FIG. 1 is a schematic diagram showing an example of an apparatus for carrying out step (2) of the present invention.

[0010] The present invention will be described in detail below. ２１１ The method for producing the At solution includes the following steps (1) and (2): Step (1): Irradiating bismuth with α-rays to form an At solution in the bismuth. ２１１ Step (2): Distilling the α-ray irradiated bismuth, ２１１ A step of separating and purifying At and dissolving it in an aqueous sodium bicarbonate solution

[0011] In step (1), bismuth is irradiated with α-rays using an accelerator (e.g., a cyclotron). Any accelerator capable of accelerating α-rays to 30 MeV can be used. Step (1) can be performed, for example, by the following method. A target material is prepared by thinly coating bismuth on an aluminum plate (e.g., approximately 30 mm wide x 70 mm long x 2 mm) using a vapor deposition method. Helium ions (1 to 50 μA) are accelerated to approximately 28 MeV in a cyclotron and irradiated onto the target material for 10 minutes to 24 hours. ２０９ Bi ( ４ He, 2n) ２１１ By the nuclear reaction of At ２１１ At is produced. ２１１At is embedded in the bismuth target material.

[0012] A schematic diagram showing an example of an apparatus for carrying out step (2) is shown in FIG. 1. Step (2) will be described below with reference to FIG. 1. (Dry distillation apparatus) ２１１ Separation and purification of At) Accelerator-irradiated target material ( ２１１ Specifically, a target substance placed on a high-boiling-point metal (target boat) such as nickel (Ni) or copper (Cu) is placed in a quartz tube (with the bismuth-coated surface facing upward), and a carrier gas (e.g., O ２ gas, He gas, H ２ The quartz tube is heated to a distillation temperature (e.g., 850°C) in an electric furnace, and the bismuth target material melts. ２１１ Attenuated ions are sublimated and carried by the carrier gas flow from the outlet of the quartz tube (on the right side of the quartz tube in Figure 1) via a three-way stopcock into the cooling tube. ２１１ The piping from the outlet of the quartz tube to the cooling tube via the three-way activation system is heated to about 130°C with a heater to prevent the deposition of volatile astatine oxide. ２１１ It usually takes about 1 hour for At to be completely sublimated and captured. ２１１ Recovery of At) After cooling the cooling tube in Figure 1 or returning it to room temperature, the tube is opened from the inlet on the opposite side to the side where the carrier gas was transferred (the right side of the cooling tube in Figure 1). ２１１ A sodium bicarbonate aqueous solution, which is a liquid for recovering At (hereinafter also referred to as recovery liquid), is transferred into the cooling tube, and the At captured in the cooling tube is ２１１ At is dissolved and recovered in a reaction vessel. The recovery liquid is either manually injected into a syringe or transferred using a compressed air device or vacuum pump (negative pressure) attached to the separation and purification system.

[0013] In the present invention, in step (2), the irradiated target material ( ２１１The present invention is characterized in that an aqueous sodium bicarbonate solution is used as a recovery liquid when separating and purifying a hydroxybenzoate (containing At) by dry distillation. In the present invention, the concentration of the aqueous sodium bicarbonate solution used as the recovery liquid is, for example, 0.1 to 30 wt / vol %, preferably 0.5 to 10 wt / vol %, more preferably 2 to 8 wt / vol %, and even more preferably 3 to 8 wt / vol %. As the aqueous sodium bicarbonate solution, a commercially available product can be used, for example, Meylon Intravenous Injection 7% (trade name) (Otsuka Pharmaceutical Factory, Inc.).

[0014] In the present invention, the amount of the aqueous sodium hydrogencarbonate solution used as the recovery liquid is, for example, 0.01 to 100 mL, preferably 0.1 to 30 mL, and more preferably 0.3 to 15 mL. The recovery liquid may be transferred to the cooling tube in multiple batches using the above amount.

[0015] In step (2) of the present invention, an aqueous sodium bicarbonate solution is used as the recovery liquid. ２１１ In addition to recovering At, a liquid other than aqueous sodium bicarbonate solution (e.g., water) is used as the recovery liquid. ２１１ At recovery may be combined, but at least the first ２１１ In the recovery of At (i.e., the initial transfer of the recovery liquid to the cooling tube), an aqueous sodium bicarbonate solution is used as the recovery liquid. ２１１ For the recovery of At, it is preferable to use only an aqueous sodium bicarbonate solution as the recovery liquid.

[0016] In the present invention, the aqueous sodium hydrogencarbonate solution used as the recovery liquid preferably does not contain either or both of a reducing agent (e.g., ascorbic acid) and an oxidizing agent (e.g., N-chlorosuccinimide), and it is particularly preferable that the aqueous sodium hydrogencarbonate solution does not contain both a reducing agent and an oxidizing agent. This is because the reducing agent and the oxidizing agent are ２１１ This is because the redox state of At may be changed, which may affect the subsequent labeling reaction. According to the production method of the present invention, even without using a reducing agent or an oxidizing agent, a high recovery rate can be achieved. ２１１Therefore, the At solution obtained by the production method of the present invention does not contain either a reducing agent or an oxidizing agent, or both (preferably does not contain both a reducing agent and an oxidizing agent). ２１１ The At solution can be used not only for labeling reactions of boronic acid-modified precursors and tributyltin group-modified precursors, but also for a wide range of astatination reactions in aqueous solutions.

[0017] In the present invention, after transferring the aqueous sodium bicarbonate solution as the recovery liquid to the cooling tube, the recovery liquid is retained in the cooling tube for a certain period of time (for example, 1 second or more, preferably 10 seconds or more, more preferably 30 seconds or more, and more preferably 1 minute or 5 minutes or more) (in other words, the recovery liquid and the sodium bicarbonate solution trapped in the cooling tube are retained in the cooling tube for a certain period of time (for example, 1 second or more, preferably 10 seconds or more, more preferably 30 seconds or more, and more preferably 1 minute or 5 minutes or more) ２１１ It is preferable to bring the recovery liquid into contact with the water-soluble polymer solution trapped in the cooling tube for a certain period of time (for example, 1 second or more, preferably 10 seconds or more, more preferably 30 seconds or more, and even more preferably 1 minute or 5 minutes or more). ２１１ By increasing the contact time with At ２１１ The retention time (contact time) can be set as follows: ２１１ Since At has a half-life of 7.2 hours, it gradually decays and disappears, so the time is 7 hours or less, preferably 1 hour or less, and more preferably 10 minutes or less.

[0018] In another embodiment of the present invention, instead of the sodium bicarbonate described above, a bicarbonate such as potassium bicarbonate, calcium bicarbonate, or cesium bicarbonate; a carbonate such as sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, or cesium carbonate; or a carbonate buffer solution may be used as the recovery liquid.

[0019] In the present invention, the carrier gas used in the distillation (step (2)) is an inert gas and O ２ In the present invention, the carrier gas used in the distillation (step (2)) preferably contains an inert gas and O ２ In addition to H ２ It is more preferable that O is contained.

[0020] Examples of inert gases in the carrier gas include He, Ne, Ar, Kr, Xe, and N. ２ and the like, preferably He or N ２ is.

[0021] The flow rate of the inert gas in the carrier gas is preferably 1 to 300 mL / min, more preferably 3 to 100 mL / min, and even more preferably 6 to 30 mL / min. ２ The flow rate of the carrier gas is preferably 1 to 300 mL / min, more preferably 3 to 100 mL / min, and even more preferably 6 to 10 mL / min. ２ The flow rate ratio of the inert gas in the carrier gas to O is preferably 99:1 to 1:99, more preferably 90:10 to 10:90, and even more preferably 80:20 to 30:70. ２ If the flow rate ratio or the flow rate ratio is outside the above range, astatine oxide is not produced, ２１１ This causes problems such as a decrease in the yield of At.

[0022] In the present invention, the carrier gas is H ２ When O is contained, H in the carrier gas ２ The content of O is preferably 1 to 15 μg / cm ３ and more preferably 1 to 10 μg / cm ３ and more preferably 2 to 5 μg / cm ３ H in the carrier gas ２ If the O content is outside the above range, ２１１ This causes problems such as a decrease in the yield of At.

[0023] In a preferred embodiment of the present invention, the flow rate of the inert gas in the carrier gas is 1 to 300 mL / min, and O ２ The flow rate of the carrier gas is 1 to 300 mL / min. ２ The flow rate ratio of H is 99:1 to 1:99, and ２ O content is 1 to 15 μg / cm ３In a more preferred embodiment of the present invention, the flow rate of the inert gas in the carrier gas is 3 to 100 mL / min, and the O ２ The flow rate of the carrier gas is 3 to 100 mL / min. ２ The flow rate ratio of H is 90:10 to 10:90. ２ O content is 1 to 10 μg / cm ３ In a further preferred embodiment of the present invention, the flow rate of the inert gas in the carrier gas is 6 to 30 mL / min, and the O ２ The flow rate of the carrier gas is 6 to 10 mL / min. ２ The flow rate ratio of H is 80:20 to 30:70. ２ O content is 2 to 5 μg / cm ３ is.

[0024] Inert gas and O ２ teeth, ２１１ From the viewpoint of improving the recovery rate of At, it is preferable that each of them has a high purity (for example, 99.999% or more, preferably 99.9999% or more).

[0025] In the present invention, the temperature of the quartz tube for distillation (i.e., the distillation temperature) is preferably 500 to 850°C, more preferably 650 to 850°C, and even more preferably 800 to 850°C. If the temperature of the quartz tube is outside the above range, ２１１ This causes problems such as a decrease in the yield of At.

[0026] In the present invention, the target boat for carrying the target material is used to prevent the target material from contacting the quartz tube and damaging the quartz tube. The target boat is made of a material having excellent heat resistance and corrosion resistance, such as nickel, copper, titanium, and quartz, with nickel and copper being preferred.

[0027] In the present invention, the temperature of the cooling tube is, for example, −80 to 100° C., preferably −10 to 60° C., and more preferably −3 to 25° C. In the present invention, examples of the material for the cooling tube include fluororesin (e.g., Teflon (registered trademark)) and polyether ether ketone resin (e.g., PEEK). The inner diameter of the cooling tube is, for example, 1 to 3 mm. The length of the cooling tube is, for example, 1 to 100 cm.

[0028] According to the production method of the present invention, ２１１ The At solution can be prepared by the method of the present invention. ２１１ The recovery rate of At is, for example, 60% or more, preferably 70% or more, and more preferably 80% or more. The recovery rate in the present invention can be measured and calculated by the methods described in Test Examples 1 to 3 below or methods equivalent thereto.

[0029] The method for producing the present invention ２１１ The At solution is, for example, a prostate cancer treatment drug, ２１１ At] can be used as a raw material for PSMA-5. Conventionally, an aqueous solution of a labeling precursor (PSMA-5 solution) is added with ２１１ After adding an aqueous solution of At (pure water or distilled water for injection), a 7% aqueous solution of sodium bicarbonate and a 0.1 mol / L aqueous solution of potassium iodide were further added, and the mixture was heated at 80°C for 45 minutes to react. ２１１ At]PSMA-5 was produced by the method of the present invention (WO2023 / 008556). ２１１ At solution can be obtained with high recovery rate and is used as a raw material for the above method. ２１１ Instead of an aqueous solution of At (pure water or distilled water for injection), ２１１ By using the At solution, it is expected that the cost of raw materials can be reduced.

[0030] In addition, the compound obtained by the production method of the present invention ２１１In principle, the At solution can be applied to the production of pharmaceuticals other than PSMA-5, except for compounds that are unstable in the presence of sodium bicarbonate (pH 8-9). PSMA-5 contains a boronic acid group in the molecule, and the boronic acid group undergoes a substitution reaction with astatine. Therefore, the PSMA-5 obtained by the production method of the present invention ２１１ The At solution is particularly useful in the astatination reaction of a compound containing a boronic acid group. ２１１ The At solution can also be used for the astatinization reaction of compounds containing alkyltin groups or alkylsilyl groups in addition to boronic acid groups.

[0031] The present invention also relates to a method for recovering astatine-211 (hereinafter also referred to as the recovery method of the present invention), which comprises the steps of irradiating bismuth with α-rays to produce astatine-211 in the bismuth (step (1)), and distilling the α-ray-irradiated bismuth to separate and purify astatine-211, and dissolving it in an aqueous sodium bicarbonate solution (step (2)). In the recovery method of the present invention, steps (1) and (2) can be carried out in the same manner as steps (1) and (2) of the production method of the present invention described above.

[0032] The present invention will be described in more detail below based on examples and test examples, but the present invention is not limited to these.

[0033] [Test Example 1] (Example 1) A bismuth target material was irradiated with helium ions accelerated to 28 MeV using a cyclotron. ２０９ Bi ( ４ He, 2n) ２１１ By At nuclear reaction ２１１ This target substance ( ２１１The irradiated target material (containing At, using Ni boat) was separated and purified by dry distillation. Specifically, the irradiated target material was placed in a quartz tube and heated to 850°C under a flow of a mixed gas (carrier gas) of helium (6 mL / min) and oxygen (10 mL / min) containing water (3000-4000 ppm, adjusted as needed during operation to maintain this range). The target material was then captured in a cooling tube (temperature: -3°C, made of Teflon (registered trademark), inner diameter 2 mm, length 600 mm) connected to the downstream side of the quartz tube. Next, 0.1 mL of a recovery liquid (7% aqueous sodium bicarbonate solution (Meiron Injection 7% (trade name), Otsuka Pharmaceutical Factory, Inc.)) was injected into the cooling tube from the downstream side of the cooling tube. The recovery liquid was allowed to remain in the tube for 5 minutes and then transferred to a reaction vessel. ２１１ An At solution (fraction 1) was obtained. The procedure of injecting 0.1 mL of recovery liquid (7% aqueous sodium bicarbonate solution), leaving it in the tube for 5 minutes, and transferring it to the reaction vessel was repeated four more times. ２１１ The At solution (fractions 2 to 5) was obtained. Furthermore, 5 mL of ethanol and 30 mL of distilled water for injection were sequentially injected into the cooling tube to remove the remaining ２１１ At was collected in a vial for washing. ２１１ The radioactivity in the washing solution (At solution) and the washing solution collected in the washing solution vial was measured using an RI dose calibrator (manufactured by Capin Tech), and calculated according to the following calculation formula 1: ２１１ The recovery rate in the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0034]

[0035] (Example 2) In the same manner as in Example 1, ２１１ The At solution (fractions 1 to 5) was obtained. The remaining At solution was washed with the same method as in Example 1. ２１１ At is recovered in a vial for a washing solution, and the radioactivity in the recovery solution (each fraction) transferred to the reaction vessel and the washing solution recovered in the vial for a washing solution is measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0036] (Examples 3 to 6) The procedure of "injecting 0.1 mL of recovery liquid (7% aqueous sodium bicarbonate solution), leaving it in the tube for 5 minutes, and transferring it to the reaction vessel" in Example 1 was repeated four more times. ２１１ "At solution (fractions 2 to 5) was obtained," and "the procedure of injecting 0.1 mL of recovery liquid (7% aqueous sodium bicarbonate solution), leaving it in the tube for 5 minutes, and transferring it to a reaction vessel was repeated six more times. ２１１ The same method as in Example 1 was carried out except that the At solution (fractions 2 to 7) was obtained. ２１１ The At solution (fractions 1 to 7) was obtained. The remaining At solution was washed with the same method as in Example 1. ２１１ At was recovered in a vial for washing, and the radioactivity in the recovery liquid (each fraction) transferred to the reaction vessel and the washing liquid recovered in the vial for washing was measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0037] (Example 7) The procedure in Example 1, "leaving the recovery liquid in the tube for 5 minutes," was changed to "leaving the recovery liquid in the tube for 1 minute," and the procedure in Example 1, "injecting 0.1 mL of recovery liquid (7% sodium bicarbonate aqueous solution), leaving it in the tube for 5 minutes, and transferring it to a reaction vessel," was repeated four more times. ２１１ "At solution (fractions 2 to 5) was obtained" and "the procedure of injecting 0.1 mL of recovery liquid (7% sodium bicarbonate aqueous solution), leaving it in the tube for 1 minute, and transferring it to the reaction vessel was repeated 9 more times, ２１１ The same method as in Example 1 was used except that the At solution (fractions 2 to 10) was obtained. ２１１ The At solution (fractions 1 to 10) was obtained. The remaining At solution was washed with the same method as in Example 1. ２１１ At is recovered in a vial for a washing solution, and the radioactivity in the recovery solution (each fraction) transferred to the reaction vessel and the washing solution recovered in the vial for a washing solution is measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0038] (Example 8) The procedure of "leaving the recovery liquid in the tube for 5 minutes" in Example 1 was omitted, and the procedure of "injecting 0.1 mL of recovery liquid (7% sodium bicarbonate aqueous solution), leaving it in the tube for 5 minutes, and transferring it to the reaction vessel" in Example 1 was repeated four more times. ２１１ "At solution (fractions 2 to 5) was obtained" and "the operation of injecting 0.1 mL of recovery liquid (7% aqueous sodium bicarbonate solution) and transferring to the reaction vessel was repeated 9 more times, ２１１ The same method as in Example 1 was carried out except that the At solution (fractions 2 to 10) was obtained. ２１１ The At solution (fractions 1 to 10) was obtained. The remaining At solution was washed with the same method as in Example 1. ２１１ At is recovered in a vial for a washing solution, and the radioactivity in the recovery solution (each fraction) transferred to the reaction vessel and the washing solution recovered in the vial for a washing solution is measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0039] Comparative Example 1 The same method as in Example 1 was used except that the 7% aqueous sodium bicarbonate solution used as the recovery liquid in Example 1 was changed to distilled water, and the step of "leaving the recovery liquid in the tube for 5 minutes" in Example 1 was not performed. ２１１ The At solution (fractions 1 to 5) was obtained. The remaining At solution was washed with the same method as in Example 1. ２１１ At is recovered in a vial for a washing solution, and the radioactivity in the recovery solution (each fraction) transferred to the reaction vessel and the washing solution recovered in the vial for a washing solution is measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 1.

[0040] Distilled water (water for injection) was used as the recovery liquid. ２１１ When At was recovered, the recovery rate was only 33% (Comparative Example 1). On the other hand, when 0.5 or 0.7 mL of a 7% aqueous solution of sodium bicarbonate was used as the recovery liquid and the solution was allowed to stand for 5 minutes, ２１１The recovery rate when At was recovered was the highest, ranging from 90.7 to 94.4% (Examples 1 to 6). There was no particular difference between the liquid volumes of the 7% sodium bicarbonate aqueous solution, 0.5 mL and 0.7 mL. Even when the retention time of the 7% sodium bicarbonate aqueous solution was shortened to 1 minute, the recovery rate was as high as 91.2% (Example 7). In Examples 1 to 8, the recovery rates were significantly higher than in Comparative Example 1.

[0041]

[0042] Test Example 2 Test Example 2 was carried out in the same manner as in Comparative Example 1, except that the carrier gas in Comparative Example 1 of Test Example 1, "a mixed gas of helium (6 mL / min) and oxygen (10 mL / min) to which moisture (3000 to 4000 ppm) has been added," was changed to "a mixed gas of nitrogen (30 mL / min) and oxygen (10 mL / min) to which moisture (3000 to 4000 ppm) has been added," and the number of operations of injecting 0.1 mL of recovery liquid and transferring it to the reaction vessel was changed so that the total amount of recovery liquid became the total amount of recovery liquid shown in Table 2. ２１１ At solution (fractions 1 to 4), Comparative Example 3 ２１１ At solution (fractions 1 to 3), Comparative Example 4 ２１１ At solution (fractions 1 to 4) was obtained. ２１１ The radioactivity in the solution was measured using a Ge semiconductor detector (manufactured by Canberra). After the operation, the cooling tube was removed and the radioactivity was directly measured using a Ge semiconductor detector (manufactured by Canberra). ２１１ The recovery rate of the At solution (all fractions) was calculated according to the following formula 2: ２１１ The recovery rate of the At solution (fraction 1) was calculated according to the following formula 3. The results are shown in Table 2.

[0043]

[0044]

[0045] Distilled water (water for injection) 0.3 to 0.4 mL ２１１ The recovery rate of At when recovered was 71% on average (average of Comparative Examples 2 to 4), but the recovery rate varied (57.5 to 78.5%).

[0046]

[0047] [Test Example 3] (Example 9) A bismuth target material was irradiated with helium ions accelerated to 28 MeV using a cyclotron. ２０９ Bi ( ４ He, 2n) ２１１ By At nuclear reaction ２１１ This target substance ( ２１１ The irradiated target material (containing At, Cu boat used) was separated and purified by dry distillation. Specifically, the irradiated target material was placed in a quartz tube and heated to 850°C under a flow of a mixed gas (carrier gas) of nitrogen (30 mL / min) and oxygen (10 mL / min) containing added moisture (3000-4000 ppm, adjusted as needed during operation to maintain this range). The target material was then captured in a cooling tube (temperature: -3°C, made of Teflon (registered trademark), inner diameter 2 mm x length 600 mm) connected to the downstream side of the quartz tube. Next, 0.1 mL of a recovery liquid (7% aqueous sodium bicarbonate solution (Meiron Injection 7% (trade name), Otsuka Pharmaceutical Factory, Inc.)) was injected into the cooling tube from the downstream side of the cooling tube and transferred to a reaction vessel. ２１１ An At solution (fraction 1) was obtained. The procedure of injecting 0.1 mL of the recovery liquid (7% aqueous sodium bicarbonate solution) and transferring it to the reaction vessel was repeated two more times. ２１１ At solution (fractions 2 and 3) was obtained. ２１１ The radioactivity in the solution was measured using a Ge semiconductor detector (manufactured by Canberra). After the operation, the cooling tube was removed and the radioactivity was directly measured using a Ge semiconductor detector (manufactured by Canberra). ２１１ The recovery rate of the At solution (all fractions) was calculated according to the above formula 2: ２１１ The recovery rate of the At solution (fraction 1) was calculated according to the above-mentioned formula 3. The results are shown in Table 3.

[0048] (Comparative Examples 5, 6, and 9) The recovery liquid in Example 9 was changed from 7% aqueous sodium bicarbonate solution to distilled water, and the number of times of injecting 0.1 mL of recovery liquid and transferring it to the reaction vessel was changed so that the total amount of recovery liquid was the total amount of recovery liquid shown in Table 3. ２１１ At solution (fractions 1 to 4), Comparative Example 6２１１ At solution (fractions 1 to 4), Comparative Example 9 ２１１ The At solution (fractions 1 to 4) was obtained. The recovery liquid (each fraction) transferred to the reaction vessel was collected in the same manner as in Example 9. ２１１ The radioactivity in the solution (At solution) and the radioactivity in the removed cooling tube were measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 3.

[0049] Comparative Examples 7 and 8 The same method as in Example 9 was used to recover the 7% aqueous sodium bicarbonate solution in Comparative Example 7, except that distilled water was used instead of the 7% aqueous sodium bicarbonate solution in Example 9. ２１１ At solution (fractions 1 to 3), Comparative Example 8 ２１１ The At solution (fractions 1 to 3) was obtained. The recovery liquid (each fraction) transferred to the reaction vessel was collected in the same manner as in Example 9. ２１１ The radioactivity in the solution (At solution) and the radioactivity in the removed cooling tube were measured. ２１１ The recovery rate of the At solution (all fractions) was calculated, and the results are shown in Table 3.

[0050] Distilled water (water for injection) 0.3 to 0.4 mL ２１１ The average recovery rate of At was 81.6% (average of all fractions in Comparative Examples 5 to 9). ２１１ Even when At was recovered, the recovery rate was 87% (fraction 1 of Example 9), and when an additional 0.3 mL was recovered, the highest value of 96.3% (all fractions of Example 9) was obtained.

[0051]

[0052] According to the production method of the present invention, ２１１ An At solution can be prepared.

[0053] This application is based on patent application No. 2023-187204 filed in Japan, the contents of which are incorporated in their entirety herein.

Claims

1. A method for producing an astatine-211 solution, comprising the steps of: irradiating bismuth with α-particles to produce astatine-211 in the bismuth; and distilling the α-particle-irradiated bismuth to separate and purify the astatine-211, and dissolving it in an aqueous solution of sodium bicarbonate.

2. The method according to claim 1, wherein the aqueous sodium hydrogen carbonate solution does not contain either a reducing agent or an oxidizing agent, or both.

3. The method according to claim 1, wherein the separated and purified astatine-211 is dissolved by contacting it with an aqueous solution of sodium hydrogen carbonate for 10 seconds or more.

4. The carrier gas used in the distillation is an inert gas and O ２ The method of claim 1 , comprising:

5. The carrier gas is further ２ The method according to claim 4, further comprising the step of:

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