WO2019203342A1 - Separating device, separating method, ri separation and purification system, and ri separation and purification method - Google Patents

Separating device, separating method, ri separation and purification system, and ri separation and purification method Download PDF

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WO2019203342A1
WO2019203342A1 PCT/JP2019/016800 JP2019016800W WO2019203342A1 WO 2019203342 A1 WO2019203342 A1 WO 2019203342A1 JP 2019016800 W JP2019016800 W JP 2019016800W WO 2019203342 A1 WO2019203342 A1 WO 2019203342A1
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solution
separation
metal
purification
electrode
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PCT/JP2019/016800
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French (fr)
Japanese (ja)
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勝伸 森
慎一 大平
敬 戸田
由美 須郷
渡辺　茂樹
典子 石岡
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国立大学法人高知大学
国立大学法人 熊本大学
国立研究開発法人量子科学技術研究開発機構
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Priority to JP2020514458A priority Critical patent/JP7288261B2/en
Publication of WO2019203342A1 publication Critical patent/WO2019203342A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D59/00—Separation of different isotopes of the same chemical element
    • B01D59/38—Separation by electrochemical methods
    • C—CHEMISTRY; METALLURGY
    • C22—METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22B—PRODUCTION AND REFINING OF METALS; PRETREATMENT OF RAW MATERIALS
    • C22B15/00—Obtaining copper
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • G21G4/04—Radioactive sources other than neutron sources
    • G21G4/06—Radioactive sources other than neutron sources characterised by constructional features
    • G21G4/08—Radioactive sources other than neutron sources characterised by constructional features specially adapted for medical application

Definitions

  • the present invention relates to a technique for separating and purifying radioisotopes (RI) from metals.
  • positron tomography which is used to diagnose brain function and cancer
  • a compound that is labeled with a radioisotope (RI) that emits positrons to a compound (labeled precursor) that induces the lesion is used.
  • RI radioisotope
  • a radioactive metal having an appropriate half-life such as 64 Cu (half-life of 12.7 hours) (longer than a widely used 18 F (half-life of 110 minutes) or the like) has attracted attention.
  • 64 Cu half-life of 12.7 hours
  • 18 F half-life of 110 minutes
  • Patent Document 1 discloses a general method for producing 64 Cu.
  • FIG. 11 is a flowchart showing a procedure of a general method for producing 64 Cu.
  • 64 Cu is obtained by irradiating a 64 Ni raw material with a proton beam (for example, about 2 hours).
  • the replacement step (S102) After the mixture of 64 Ni and 64 Cu is dissolved by heating, in the replacement step (S102), it takes about 1 hour to repeat evaporation and drying and re-dissolution of the dissolved product.
  • the separation step (S103) it takes about 30 minutes to 1 hour in order to separate 64 Ni and 64 Cu using chromatography in a hydrochloric acid system.
  • the purification step (S104) evaporation to dryness (about 1 hour) for removal of hydrochloric acid and dissolution with ultrapure water are performed, and the separation and purification of 64 Cu is completed. Thereafter, the separated and purified 64 Cu is made into a drug by reacting with a labeling precursor (about 1 to 2 hours) and used for PET diagnosis.
  • the irradiation step when the irradiation step is included, it may take 7 hours or more until a 64 Cu drug is obtained, which is a heavy burden for the medical site.
  • This invention is made in view of the said problem, and makes it a subject to provide the technique which isolate
  • RI can be separated in a very short time by an electrochemical method in which a voltage is applied to a solution containing a metal and its RI.
  • Item 1 A separation device for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal, An electrode for applying a predetermined voltage to the first solution; The separation apparatus, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
  • Item 2. Item 2. The separation device according to Item 1, wherein the metal is Ni and the RI is Cu.
  • Item 3. Item 2. The separation apparatus according to Item 1, wherein the metal is Zn and the RI is Cu.
  • the separation apparatus according to any one of Items 1 to 3, further comprising recovery means for dissolving the RI electrodeposited on the electrode in the second solution and recovering the RI from the separation apparatus.
  • Item 5. Item 4. The separation device according to Item 4, A purification device for purifying the RI from the second solution; RI separation and purification system.
  • Item 6. A separation method for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal, An application step of applying a predetermined voltage to the first solution via an electrode; The separation method, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
  • Item 7. Item 7.
  • Item 7. The separation method according to Item 6, wherein the metal is Zn and the RI is Cu.
  • Item 9. The separation method according to any one of Items 6 to 8, further comprising a recovery step in which the RI electrodeposited on the electrode is dissolved in a second solution and recovered from the separation device.
  • Item 10. Each step of the separation method according to Item 9, A purification step of purifying the RI from the second solution; RI separation and purification method.
  • metal RI can be separated in a short time.
  • Is a graph showing the Zn (II) and electrodeposition rate of Cu (II) dissolved in 100mM solution of HNO 3, the relationship between the applied voltage to the electrode.
  • HNO 3 solution and 10 mM HNO 3 in 100mM is a graph showing the relationship between the recovery rate and the applied voltage at the time of electrodeposition of Cu (II).
  • A) to (c) show the relationship between the extraction rate of Cu (II) in the eluates AA, SC and CA and the applied voltage between the electrodes when a 10 mM HNO 3 solution is used as the acceptor solution. It is a graph to show.
  • (A) to (c) are the extraction ratio of Cu (II) in the eluate AA, SC, CA and the applied voltage between the electrodes when a 10 mM CH 3 CO 2 H solution was used as the acceptor solution. It is a graph which shows the relationship. It is a flowchart which shows the procedure of the manufacturing method of a general 64 Cu. It is a graph which shows the density
  • FIG. 1 is a block diagram showing a schematic configuration of an RI manufacturing system 100 according to this embodiment
  • FIG. 2 is a flowchart showing a procedure of an RI manufacturing method according to this embodiment.
  • the RI manufacturing system 100 includes an irradiation apparatus 10 and an RI separation and purification system 20.
  • the RI separation and purification system 20 includes a separation device 3 and a purification device 4.
  • the irradiation step S ⁇ b> 1 is performed using the irradiation apparatus 10.
  • the irradiation device 10 includes a cyclotron 1 and an irradiation metal 2.
  • the metal 2 for irradiation consists of 64 Ni of a stable stable isotope.
  • the irradiation metal 2 is irradiated from the cyclotron 1 with a proton beam. Thereby, a part of 64 Ni is converted into 64 Cu which is RI by the 64 Ni (p, n) 64 Cu reaction. Thereafter, 64 Ni and 64 Cu mixed in the irradiation metal 2 are dissolved in the first solution.
  • the first solution for example, an aqueous solution containing a strong acid such as HNO 3 or HCl can be used. The first solution is transferred to the RI separation and purification system 20.
  • the separation step S2, the recovery step S3, and the purification step S4 in the RI separation and purification method according to the present embodiment are performed using the RI separation and purification system 20.
  • the separation device 3 includes an electrode for applying a predetermined voltage to the first solution.
  • the predetermined voltage is a voltage in which the electrodeposition rate of 64 Ni to the electrode is different from the electrodeposition rate of 64 Cu to the electrode.
  • FIG. 3 is a schematic cross-sectional view showing an example of the separation device 3.
  • the separation device 3 is composed of a flow column type electrolytic synthesis cell.
  • the separation device 3 includes a working electrode 31 made of carbon fiber and a counter electrode 32 made of platinum wire as electrodes. A voltage is applied to the working electrode 31 via an electrode rod 33 connected to the terminal 34. A voltage is applied to the counter electrode 32 from a terminal 35.
  • the working electrode 31 is filled inside the porous glass tube 36, and the counter electrode 32 is wound around the porous glass tube 36.
  • a reference voltage for keeping the voltage applied to the working electrode 31 and the counter electrode 32 at a constant potential is applied to the terminal 37.
  • the first solution is introduced into the porous glass tube 36 through the introduction pipe 38 and passes through the working electrode 31.
  • the first solution is introduced into the porous glass tube 36 through the introduction pipe 38 and passes through the working electrode 31.
  • the working electrode 31 and the counter electrode 32 by applying a predetermined voltage between the working electrode 31 and the counter electrode 32 via the terminal 34 and the terminal 35, only 64 Cu is electrodeposited on the working electrode 31 by an electrolytic reaction.
  • 64 Cu which is RI is separated from the first solution.
  • FIG. 4 is a graph showing the relationship between the electrodeposition rate of Ni (II) and Cu (II) and the voltage applied to the electrode when the first solution is 10 mM HNO 3
  • FIG. is a graph showing the case where the first solution is HNO 3 in 100 mM, and electrodeposition rate of Ni (II) and Cu (II), the relationship between the applied voltage to the electrode.
  • Cu and Ni have different standard oxidation-reduction potentials (Cu + 0.340V, Ni-0.257V)
  • the electrodeposition characteristics with respect to the applied voltage are different from each other.
  • the electrodeposition characteristics with respect to the applied voltage of metal ions are the same among isotopes of the same element. Therefore, the voltage applied to the electrodes, by which the electrodeposition rate of Ni (II) electrodeposition rate and Cu (II) is a different voltage, 64 Cu from the first solution 64 Cu and 64 Ni were dissolved Can be separated.
  • the electrodeposition characteristics with respect to the applied voltage include strong acids such as HNO 3 and HCl as the first solution type when separating Ni (II) from Cu (II) from the viewpoint of separating RI with higher accuracy. It is preferable to use an aqueous solution.
  • the concentration of the first solution is preferably adjusted to 10 to 100 mM.
  • the applied voltage is preferably ⁇ 0.5 to ⁇ 0.1 V, particularly preferably ⁇ 0.4 to ⁇ 0.3 V.
  • the metal electrodeposition rate (%) is (Initial concentration of metal in the first solution introduced from the introduction pipe 38-concentration of metal in the first solution discharged from the discharge pipe 39) / (first concentration introduced from the introduction pipe 38) Initial concentration of metal in solution) x 100 It can be expressed as
  • the recovery step S3 64 Cu electrodeposited on the working electrode 31 is dissolved in the second solution and recovered from the separation device 3.
  • the first solution is taken out from the discharge pipe 39 by a collecting means (not shown), and then the second solution is introduced from the introduction pipe 38.
  • the second solution an aqueous solution containing a strong acid such as HNO 3 or HCl can be used. It is preferable to apply a positive voltage to the working electrode 31 when 64 Cu is dissolved in the second solution. By removing the second solution in which 64 Cu is dissolved from the discharge pipe 39, 64 Cu can be recovered from the separation device 3.
  • 64 Ni is very expensive (about 5,000 yen / mg)
  • 64 Ni dissolved in the first solution taken out from the discharge pipe 39 is reused for the production of 64 Cu. It is preferable to do.
  • the purification device 4 can be constituted by, for example, an electrodialysis purification device (ED).
  • FIG. 6 is a schematic diagram showing an example of the purification apparatus 4 configured by ED.
  • the purification apparatus 4 has a five-layer structure including an anode channel 41, an AA (anion acceptor) channel 42, an SC (introduction channel) 43, a CA (cation acceptor) channel 44, and a cathode channel 45.
  • the cathode channel 45 is provided with an anode 46 and a cathode 47, respectively.
  • the anode channel 41 and the AA channel 42 are separated by a cation exchange membrane F1
  • the CA channel 44 and the cathode channel 45 are separated by an anion exchange membrane F2.
  • the AA channel 42 and the introduction channel 43, and the introduction channel 43 and the CA channel 44 are separated by the regenerated cellulose membrane F3.
  • An isolator is passed through the anode channel 41 and the cathode channel 45.
  • deionized water can be used.
  • An anion acceptor and a cation acceptor are passed through the AA channel 42 and the CA channel 44, respectively.
  • a strong acid such as HNO 3 or a weak acid such as acetic acid (CH 3 CO 2 H) can be used.
  • the second solution is passed through the introduction channel 43.
  • the second solution is an HNO 3 solution in which 64 Cu is dissolved
  • the Cu (II) in the second solution is changed from NO 3 ⁇ .
  • a solvent for example, acetate buffer solution
  • 64 Cu can be purified from the second solution in the purification step S4.
  • the purification device 4 may have a four-layer structure that does not include the AA channel 42. In the case of a four-layer structure, NO 3 ⁇ passes through the introduction channel 43.
  • the 64 Cu is then transferred to the drug synthesizer and reacts with the labeling precursor. Thereby, a high purity Cu label
  • medical agent is obtained.
  • the purity test for the Cu-labeled drug can be performed by high performance liquid chromatography (HPLC) using a reverse phase or size exclusion column.
  • the irradiation step S1 is about 2 hours, which is the same as the irradiation step S101 (FIG. 11) in the prior art, but the separation step S2 and the recovery step S3 are about 5 minutes.
  • the purification step S4 is also about 5 minutes. That is, the time required for the separation steps S2 to S4 is about 10 minutes, and the time can be significantly shortened compared to the time required for the replacement step S102 to the purification step S104 (about 3 hours 30 minutes) in the prior art. . Therefore, in this embodiment, RI can be separated and purified in a short time, and severe time restrictions for handling radiopharmaceuticals can be eliminated.
  • the production amount of RI used for drug synthesis is small, the amount of liquid passing through each channel of the purification apparatus 4 used in the purification step S4 can be small. For this reason, the refining device 4 can be easily downsized, and the refining device 4 according to the present embodiment has a size of about 11 cm long ⁇ 3 cm wide ⁇ 2.5 cm high. Therefore, the scale of the RI separation and purification system 20 can be reduced, and it is possible to contribute to the elimination of spatial restrictions at the medical site.
  • the apparatus used in the substitution process S102 to the purification process S104 of the prior art has a large scale for handling 64 Cu, and loss and reaction due to purification. There was a drop in efficiency.
  • RI can be separated and purified with high efficiency by reducing the system scale according to the amount of 64 Cu produced.
  • the irradiation device 10 and the separation device 3 and the separation device 3 and the purification device 4 are seamlessly connected. Thereby, the irradiation step S1 to the purification step S4 shown in FIG. 2 can be carried out continuously, and RI can be further separated and purified.
  • the metal and RI were 64 Ni and 64 Cu, respectively, but the present invention is not limited to this. Any electrodeposition characteristic (standard oxidation-reduction potential) to the electrode with respect to the voltage applied to the solution can be applied to the present invention as long as the metal is different from RI.
  • the metal is Ni or Zn and the RI is Cu.
  • 63 Cu and 66 Ga standard redox potential -0.529 V
  • 67 Zn standard redox potential -0.763 V
  • 67 Cu and 68 Zn (standard Redox potential -0.763 V) and 67 Cu.
  • 66 Ga is useful for PET diagnosis because it has a half-life of 9.4 hours and emits positrons. Since 67 Cu has a half-life of 61.8 hours and emits ⁇ rays, it is useful for internal therapy of cancer.
  • FIG. 7 is a graph showing the relationship between the electrodeposition rates of Zn (II) and Cu (II) dissolved in a 100 mM HNO 3 solution and the voltage applied to the electrodes. Since Cu and Zn have different standard redox potentials, the electrodeposition characteristics with respect to the applied voltage are different from each other. Therefore, the voltage applied to the electrode is such that the electrodeposition rate of Zn (II) and the electrodeposition rate of Cu (II) are different, so that 67 Cu and 67 Zn or 67 Cu and 68 Zn are dissolved. 67 Cu can be separated from one solution.
  • Example 1 In Example 1, an experiment for separating Cu (II) from a first solution containing Ni (II) and Cu (II) was performed using the separation device 3 according to the above embodiment.
  • the first solution a solution prepared by dissolving 6.0 ⁇ M Ni (II) and 6.0 ⁇ M Cu (II) in a 100 mM HNO 3 solution and a solution dissolved in a 10 mM HNO 3 solution are used. Two were prepared. The first solution was introduced into the porous glass tube 36 through the introduction pipe 38 of the separation device 3. The flow rate of the first solution was 1.0 mL / min. In a state where the first solution was passed through the porous glass tube 36, a voltage was applied between the electrodes 31 and 32, and the first solution was taken out from the discharge pipe 39.
  • FIG. 8 is a graph showing the relationship between the recovery rate of Cu (II) and the applied voltage during electrodeposition when a 100 mM HNO 3 solution and 10 mM HNO 3 are used as the first solution.
  • the recovery rate was very high by setting the applied voltage to ⁇ 0.5 to ⁇ 0.2V.
  • the recovery rate became very high when the applied voltage was -0.5 to -0.3 V.
  • Example 1 general reagents, ie, Ni and Cu of natural composition (hereinafter referred to as natNi and natCu) were used, but the electrodeposition characteristics of dissolved metal ions with respect to the applied voltage are the same between isotopes of the same element. . That is, the electrodeposition characteristics of nat Ni (II) and 64 Ni (II) (mainly nat Ni 2+ and 64 Ni 2+ ) are the same, and nat Cu (II) and 64 Cu (II) (mainly nat Cu 2+ And 64 Cu 2+ ) have the same electrodeposition characteristics. Therefore, it was found that 64 Cu can be separated with high efficiency from the first solution containing 64 Ni and 64 Cu by using the separation device 3.
  • natNi and natCu the electrodeposition characteristics of dissolved metal ions with respect to the applied voltage are the same between isotopes of the same element. . That is, the electrodeposition characteristics of nat Ni (II) and 64 Ni (II) (mainly
  • the recovery rate (%) is (Cu (II) concentration in the second solution discharged from the discharge pipe 39 in the recovery step) / (Cu (II) initial concentration in the first solution introduced from the introduction pipe 38 in the separation step)) ⁇ 100 It is calculated by. Therefore, when Cu (II) is recovered in a concentrated state, the recovery rate exceeds 100%.
  • Example 2 In Example 2, an experiment for purifying Cu from the second solution was performed using the purification apparatus 4 according to the above embodiment.
  • an electrodialysis purification device having a five-layer structure shown in FIG. 6 was used as the purification device 4.
  • Deionized water is passed through the anode channel 41 and the cathode channel 45 as an isolator, and a 10 mM HNO 3 solution or CH 3 CO 2 H solution is passed through the AA channel 42 and the CA channel 44 as an acceptor solution,
  • the second solution was passed through the introduction channel 43.
  • an HNO 3 solution in which 5.0 ⁇ M Cu (II) (mainly in the form of Cu 2+ ) was dissolved was used as the second solution.
  • the extraction rate (%) is (Metal concentration in solution introduced into channel 43 ⁇ metal concentration in solution eluted from each channel 42, 43, 44) / (metal concentration in solution introduced into channel 43) ⁇ 100 It can be expressed as
  • FIGS. 9A to 9C show the extraction rate of Cu (II) in the eluents AA, SC, and CA and the application between the electrodes 46 and 47, respectively, when a 10 mM HNO 3 solution is used as the acceptor solution. It is a graph which shows the relationship with a voltage. In this case, it was found that Cu (II) can be extracted from the eluent CA from the channel 44 with higher efficiency as the applied voltage is increased.
  • 10 (a) to 10 (c) show the extraction ratio of Cu (II) in the eluate AA, SC, CA and the distance between the electrodes 46, 47 when a 10 mM CH 3 CO 2 H solution is used as the acceptor solution. It is a graph which shows the relationship with the applied voltage to. In this case, an extraction rate close to 100% could be achieved by setting the applied voltage to 5 to 10V.
  • Example 2 the concentration of Cu (II) was adjusted in accordance with the lower limit of quantification of the detector (atomic absorption). However, if this concentration is further reduced, it dissolves even in basic, so in a wider range. It is considered that Cu (II) can be purified with an applied voltage.
  • Example 3 In Example 3, an experiment for separating 64 Cu (II) from a first solution containing 57 Ni (II) and 64 Cu (II) was performed using the separation apparatus 3 according to the above embodiment.
  • Example 1 a column type electrolytic synthesis cell (electrolytic synthesis / analysis column type flow cell HX-201) manufactured by Hokuto Denko Co., Ltd. was used as in Example 1.
  • the first solution a solution prepared by dissolving 57 Ni (II) and 64 Cu (II) obtained by proton beam irradiation on nickel oxide in 5 mL of 100 mM HCl solution was prepared.
  • the first solution was introduced into the porous glass tube 36 through the introduction pipe 38 of the separation device 3.
  • a voltage of ⁇ 0.6 V was applied between the electrodes 31 and 32, and the solution was taken out from the discharge pipe 39 in two portions of 2 mL.
  • the second solution was passed through the porous glass tube 36, and the solution was taken out from the discharge pipe 39 in 2 mL portions in two portions. Further, in order to elute 64 Cu electrodeposited on the working electrode 31, the voltage applied between the electrodes 31 and 32 is switched from -0.6V to + 0.6V, and the second solution is put into the porous glass tube 36. While passing through the solution, the solution was taken out from the discharge pipe 39 in two portions of 2 mL. As the second solution, a 100 mM HNO 3 solution was used.
  • FIG. 12 is a graph showing the concentrations of 57 Ni (II) and 64 Cu (II) in the solution taken out from the discharge pipe 39.
  • the horizontal axis indicates the order in which the solutions are removed.
  • 64 Cu (II) of the first solution is electrodeposited on the working electrode 31, so only about 57 Ni (II) is detected in the solution taken out the first to fourth times. It was.
  • the concentration of 57 Ni (II) is low because the ratio of the solution present in the analyzer 3 before introducing the first solution is high. Since the total amount of the first solution introduced into the first solution is 5 mL, the concentration of 57 Ni (II) reaches a maximum with the solution taken out for the second time and then gradually decreases. Was hardly detected in the removed solution.
  • Example 4 In Example 4, an experiment for purifying 64 Cu (II) from the second solution was performed using the purification apparatus 4 according to the above embodiment.
  • the electrodialysis purification apparatus 4 As the purification apparatus 4, the electrodialysis purification apparatus having a five-layer structure shown in FIG. As a pre-process, after deionized water is passed through all the channels 41 to 45, a voltage of 15 V is applied between the electrodes 46 and 47, and then pure water is passed through the anode channel 41 and the cathode channel 45 as an isolator. A 10 mM CH 3 CO 2 H solution was passed as an acceptor solution through the AA channel 42 and the CA channel 44, and a second solution was passed through the introduction channel 43. As the second solution, a 10 mM HCl solution in which 64 Cu (II) was dissolved was used.
  • FIGS. 13A to 13C are graphs showing the extraction rate of 64 Cu (II) in the eluents AA, SC, and CA, respectively.
  • the horizontal axis indicates the order in which the solutions are removed.
  • the eluate CA taken out for the first to third times has an extraction rate of 10 to 20%, which is considered to be due to adsorption of 64 Cu (II) to the CA channel 44.
  • the extraction rate exceeds 100%. This is because H + moves to the CA channel 44 by passing HCl through the introduction channel 43, This is probably because the pH in the CA channel 44 dropped and 64 Cu (II) adsorbed on the CA channel 44 was dissolved.
  • FIG. 14 is a table showing the contents of metal elements other than Ni and Cu after passing through the purification apparatus 4.
  • the unit is mg / L, and “ ⁇ ” indicates that the content is below the detection limit. Further, “ ⁇ 0.001” or “ ⁇ 0.002” indicates that the value is below the lower limit of quantification.
  • Each numerical value shown in FIG. 14 is a level at which there is no problem in clinical practice.
  • the metals shown in FIG. 14 are contained in nickel oxide and air, and are inevitably mixed into the first and second solutions in the manufacturing process of radioactive metals, but these metals are removed by the purifier 4. I found out.

Abstract

The objective of the present invention is to separate a metal RI in a short time. A separating device 3 for separating a radioisotope (RI) from a first solution containing a metal and the RI, obtained by transformation of the metal, is provided with an electrode 31 for applying a prescribed voltage to the first solution, wherein the prescribed voltage is a voltage with which a rate of electrodeposition of the metal onto the electrode 31 is different from the rate of electrodeposition of the RI onto the electrode 31.

Description

分離装置、分離方法、ＲＩ分離精製システムおよびＲＩ分離精製方法Separation apparatus, separation method, RI separation and purification system, and RI separation and purification method
　本発明は、金属から放射性同位体（ＲＩ）を分離・精製する技術に関する。 The present invention relates to a technique for separating and purifying radioisotopes (RI) from metals.
　脳機能やがんの診断に用いられるポジトロン断層撮影法（ＰＥＴ）では、病巣へ誘導する化合物（標識前駆体）に陽電子を放出する放射性同位体（ＲＩ：radioisotope）を標識した薬剤が用いられている。近年ではそのようなＲＩとして、特に６４Ｃｕ（半減期１２．７時間）等の適度な半減期（汎用されている１８Ｆ（半減期１１０分）などに比べて長い）を有する放射性金属が注目されている。 In positron tomography (PET), which is used to diagnose brain function and cancer, a compound that is labeled with a radioisotope (RI) that emits positrons to a compound (labeled precursor) that induces the lesion is used. Yes. In recent years, as such RI, a radioactive metal having an appropriate half-life such as 64 Cu (half-life of 12.7 hours) (longer than a widely used 18 F (half-life of 110 minutes) or the like) has attracted attention. Has been.
　例えば、特許文献１、非特許文献１および非特許文献２に、一般的な６４Ｃｕの製造方法が開示されている。図１１は、一般的な６４Ｃｕの製造方法の手順を示すフローチャートである。当該方法では、まず照射工程（Ｓ１０１）において、６４Ｎｉ原料へ陽子ビームを照射することにより６４Ｃｕを得る（例えば約２時間）。６４Ｎｉと６４Ｃｕの混合物を加熱溶解した後、置換工程（Ｓ１０２）では、溶解物の蒸発乾固と再溶解を繰り返すため、約１時間を要する。分離工程（Ｓ１０３）では、塩酸系でのクロマトグラフィーを用いた６４Ｎｉと６４Ｃｕの分離を行うために、約３０分～１時間を要する。精製工程（Ｓ１０４）では、塩酸除去のための蒸発乾固（約１時間）および超純水での溶解を行い、６４Ｃｕの分離精製は完了する。その後、分離精製された６４Ｃｕは標識前駆体と反応することにより薬剤化され（約１～２時間）、ＰＥＴ診断に用いられる。 For example, Patent Document 1, Non-Patent Document 1, and Non-Patent Document 2 disclose a general method for producing 64 Cu. FIG. 11 is a flowchart showing a procedure of a general method for producing 64 Cu. In this method, first, in the irradiation step (S101), 64 Cu is obtained by irradiating a 64 Ni raw material with a proton beam (for example, about 2 hours). After the mixture of 64 Ni and 64 Cu is dissolved by heating, in the replacement step (S102), it takes about 1 hour to repeat evaporation and drying and re-dissolution of the dissolved product. In the separation step (S103), it takes about 30 minutes to 1 hour in order to separate 64 Ni and 64 Cu using chromatography in a hydrochloric acid system. In the purification step (S104), evaporation to dryness (about 1 hour) for removal of hydrochloric acid and dissolution with ultrapure water are performed, and the separation and purification of 64 Cu is completed. Thereafter, the separated and purified 64 Cu is made into a drug by reacting with a labeling precursor (about 1 to 2 hours) and used for PET diagnosis.
特許第５８８０９３１号Patent No. 5880931
　以上のように、従来の方法では、照射工程も含めると６４Ｃｕの薬剤が得られるまで７時間以上を要する場合もあり、医療現場にとっては大きな負担となっている。 As described above, in the conventional method, when the irradiation step is included, it may take 7 hours or more until a 64 Cu drug is obtained, which is a heavy burden for the medical site.
　本発明は、上記問題に鑑みてなされたものであり、短時間で金属のＲＩを分離する技術を提供することを課題とする。 This invention is made in view of the said problem, and makes it a subject to provide the technique which isolate | separates RI of metal in a short time.
　本発明者らは、鋭意研究を重ねた結果、金属とそのＲＩを含む溶液に電圧を印加するという電気化学的な手法により、非常に短時間でＲＩを分離できることを見出した。 As a result of intensive studies, the present inventors have found that RI can be separated in a very short time by an electrochemical method in which a voltage is applied to a solution containing a metal and its RI.
　本発明はかかる知見に基づいて完成したものであり、下記の態様を有する。
項１．
　金属と当該金属から変換されてなる放射性同位体（ＲＩ）とを含む第１の溶液から前記ＲＩを分離する分離装置であって、
　前記第１の溶液に所定の電圧を印加するための電極を備え、
　前記所定の電圧は、前記金属の前記電極への電着率と前記ＲＩの前記電極への電着率とが異なる電圧である、分離装置。
項２．
　前記金属はＮｉであり、前記ＲＩはＣｕである、項１に記載の分離装置。
項３．
　前記金属はＺｎであり、前記ＲＩはＣｕである、項１に記載の分離装置。
項４．
　前記電極に電着した前記ＲＩを第２の溶液に溶解させて前記分離装置から回収する回収手段をさらに備える、項１～３のいずれかに記載の分離装置。
項５．
　項４に記載の分離装置と、
　前記第２の溶液から前記ＲＩを精製する精製装置と、
を備えた、ＲＩ分離精製システム。
項６．
　金属と当該金属から変換されてなる放射性同位体（ＲＩ）とを含む第１の溶液から前記ＲＩを分離する分離方法であって、
　電極を介して前記第１の溶液に所定の電圧を印加する印加工程を備え、
　前記所定の電圧は、前記金属の前記電極への電着率と前記ＲＩの前記電極への電着率とが異なる電圧である、分離方法。
項７．
　前記金属はＮｉであり、前記ＲＩはＣｕである、項６に記載の分離方法。
項８．
　前記金属はＺｎであり、前記ＲＩはＣｕである、項６に記載の分離方法。
項９．
　前記電極に電着した前記ＲＩを第２の溶液に溶解させて前記分離装置から回収する回収工程をさらに備える、項６～８のいずれかに記載の分離方法。
項１０．
　項９に記載の分離方法の各工程と、
　前記第２の溶液から前記ＲＩを精製する精製工程と、
を備えた、ＲＩ分離精製方法。 The present invention has been completed based on such findings and has the following aspects.
Item 1.
A separation device for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal,
An electrode for applying a predetermined voltage to the first solution;
The separation apparatus, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
Item 2.
Item 2. The separation device according to Item 1, wherein the metal is Ni and the RI is Cu.
Item 3.
Item 2. The separation apparatus according to Item 1, wherein the metal is Zn and the RI is Cu.
Item 4.
Item 4. The separation apparatus according to any one of Items 1 to 3, further comprising recovery means for dissolving the RI electrodeposited on the electrode in the second solution and recovering the RI from the separation apparatus.
Item 5.
Item 4. The separation device according to Item 4,
A purification device for purifying the RI from the second solution;
RI separation and purification system.
Item 6.
A separation method for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal,
An application step of applying a predetermined voltage to the first solution via an electrode;
The separation method, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
Item 7.
Item 7. The separation method according to Item 6, wherein the metal is Ni and the RI is Cu.
Item 8.
Item 7. The separation method according to Item 6, wherein the metal is Zn and the RI is Cu.
Item 9.
Item 9. The separation method according to any one of Items 6 to 8, further comprising a recovery step in which the RI electrodeposited on the electrode is dissolved in a second solution and recovered from the separation device.
Item 10.
Each step of the separation method according to Item 9,
A purification step of purifying the RI from the second solution;
RI separation and purification method.
　本発明によれば、短時間で金属のＲＩを分離することができる。 According to the present invention, metal RI can be separated in a short time.
本実施形態に係るＲＩ製造システムの概略構成を示すブロック図である。It is a block diagram which shows schematic structure of RI manufacturing system which concerns on this embodiment. 本実施形態に係るＲＩ製造方法の手順を示すフローチャートである。It is a flowchart which shows the procedure of the RI manufacturing method which concerns on this embodiment. 分離装置の一例を示す概略断面図である。It is a schematic sectional drawing which shows an example of a separation apparatus. 第１の溶液が１０ｍＭのＨＮＯ３である場合の、Ｎｉ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフである。When the first solution is HNO 3 in 10 mM, and electrodeposition rate of Ni (II) and Cu (II), is a graph showing the relationship between the applied voltage to the electrode. 第１の溶液が１００ｍＭのＨＮＯ３である場合の、Ｎｉ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフである。When the first solution is HNO 3 in 100 mM, and electrodeposition rate of Ni (II) and Cu (II), is a graph showing the relationship between the applied voltage to the electrode. ＥＤで構成された精製装置の一例を示す概略図である。It is the schematic which shows an example of the refiner | purifier comprised by ED. １００ｍＭのＨＮＯ３溶液に溶解したＺｎ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフである。Is a graph showing the Zn (II) and electrodeposition rate of Cu (II) dissolved in 100mM solution of HNO 3, the relationship between the applied voltage to the electrode. 第１の溶液として１００ｍＭのＨＮＯ３溶液および１０ｍＭのＨＮＯ３を用いた場合の、Ｃｕ（ＩＩ）の回収率と電着時の印加電圧との関係を示すグラフである。In the case of using a HNO 3 solution and 10 mM HNO 3 in 100mM as the first solution is a graph showing the relationship between the recovery rate and the applied voltage at the time of electrodeposition of Cu (II). （ａ）～（ｃ）はそれぞれ、アクセプター溶液として１０ｍＭのＨＮＯ３溶液を用いた場合の、溶出液ＡＡ，ＳＣ，ＣＡにおけるＣｕ（ＩＩ）の抽出率と電極間への印加電圧との関係を示すグラフである。(A) to (c) show the relationship between the extraction rate of Cu (II) in the eluates AA, SC and CA and the applied voltage between the electrodes when a 10 mM HNO 3 solution is used as the acceptor solution. It is a graph to show. （ａ）～（ｃ）はそれぞれ、アクセプター溶液として１０ｍＭのＣＨ３ＣＯ２Ｈ溶液を用いた場合の、溶出液ＡＡ，ＳＣ，ＣＡにおけるＣｕ（ＩＩ）の抽出率と電極間への印加電圧との関係を示すグラフである。(A) to (c) are the extraction ratio of Cu (II) in the eluate AA, SC, CA and the applied voltage between the electrodes when a 10 mM CH 3 CO 2 H solution was used as the acceptor solution. It is a graph which shows the relationship. 一般的な６４Ｃｕの製造方法の手順を示すフローチャートである。It is a flowchart which shows the procedure of the manufacturing method of a general 64 Cu. 分離装置から取り出された溶液中の５７Ｎｉ（ＩＩ）および６４Ｃｕ（ＩＩ）の濃度を示すグラフである。It is a graph which shows the density | concentration of 57 Ni (II) and 64 Cu (II) in the solution taken out from the separator. （ａ）～（ｃ）はそれぞれ、溶出液ＡＡ，ＳＣ，ＣＡにおける６４Ｃｕ（ＩＩ）の抽出率を示すグラフである。(A) to (c) are graphs showing the extraction rate of 64 Cu (II) in the eluents AA, SC, and CA, respectively. 精製装置を通過した後の、ＮｉおよびＣｕ以外の金属元素の含有量を示す表である。It is a table | surface which shows content of metal elements other than Ni and Cu after passing a refiner | purifier.
　以下、本発明の実施形態について添付図面を参照して説明する。下記の実施形態では、６４ＮｉからＲＩである６４Ｃｕを製造する形態について説明する。 Embodiments of the present invention will be described below with reference to the accompanying drawings. In the following embodiment, an embodiment for producing 64 Cu which is RI from 64 Ni will be described.
　〔ＲＩ製造システム・方法〕
　図１は、本実施形態に係るＲＩ製造システム１００の概略構成を示すブロック図であり、図２は、本実施形態に係るＲＩ製造方法の手順を示すフローチャートである。ＲＩ製造システム１００は、照射装置１０およびＲＩ分離精製システム２０を備えている。ＲＩ分離精製システム２０は、分離装置３および精製装置４を備えている。 [RI manufacturing system and method]
FIG. 1 is a block diagram showing a schematic configuration of an RI manufacturing system 100 according to this embodiment, and FIG. 2 is a flowchart showing a procedure of an RI manufacturing method according to this embodiment. The RI manufacturing system 100 includes an irradiation apparatus 10 and an RI separation and purification system 20. The RI separation and purification system 20 includes a separation device 3 and a purification device 4.
　本実施形態に係るＲＩ製造方法では、まず、照射装置１０を用いて照射工程Ｓ１を実施する。照射装置１０は、サイクロトロン１および照射用金属２を備えている。照射用金属２は、濃縮安定同位体の６４Ｎｉからなる。 In the RI manufacturing method according to the present embodiment, first, the irradiation step S <b> 1 is performed using the irradiation apparatus 10. The irradiation device 10 includes a cyclotron 1 and an irradiation metal 2. The metal 2 for irradiation consists of 64 Ni of a stable stable isotope.
　照射工程Ｓ１では、サイクロトロン１から陽子ビームを照射用金属２に照射する。これにより、６４Ｎｉ（ｐ，ｎ）６４Ｃｕ反応によって、６４Ｎｉの一部がＲＩである６４Ｃｕに変換される。その後、照射用金属２中に混在した６４Ｎｉと６４Ｃｕを第１の溶液に溶解させる。第１の溶液としては、例えばＨＮＯ３やＨＣｌ等の強酸を含む水溶液を用いることができる。第１の溶液は、ＲＩ分離精製システム２０に移送される。 In the irradiation step S1, the irradiation metal 2 is irradiated from the cyclotron 1 with a proton beam. Thereby, a part of 64 Ni is converted into 64 Cu which is RI by the 64 Ni (p, n) 64 Cu reaction. Thereafter, 64 Ni and 64 Cu mixed in the irradiation metal 2 are dissolved in the first solution. As the first solution, for example, an aqueous solution containing a strong acid such as HNO 3 or HCl can be used. The first solution is transferred to the RI separation and purification system 20.
　〔ＲＩ分離精製方法〕
　本実施形態に係るＲＩ製造方法では、本実施形態に係るＲＩ分離精製方法における分離工程Ｓ２、回収工程Ｓ３および精製工程Ｓ４を、ＲＩ分離精製システム２０を用いて実施する。 [RI separation and purification method]
In the RI manufacturing method according to the present embodiment, the separation step S2, the recovery step S3, and the purification step S4 in the RI separation and purification method according to the present embodiment are performed using the RI separation and purification system 20.
　（分離）
　分離工程Ｓ２では、分離装置３を用いて、６４Ｎｉと６４Ｃｕとを含む第１の溶液から６４Ｃｕを分離する。分離装置３は、第１の溶液に所定の電圧を印加するための電極を備える。前記所定の電圧は、６４Ｎｉの前記電極への電着率と６４Ｃｕの前記電極への電着率とが異なる電圧である。 (Separation)
In the separation step S2, 64 Cu is separated from the first solution containing 64 Ni and 64 Cu using the separation device 3. The separation device 3 includes an electrode for applying a predetermined voltage to the first solution. The predetermined voltage is a voltage in which the electrodeposition rate of 64 Ni to the electrode is different from the electrodeposition rate of 64 Cu to the electrode.
　図３は、分離装置３の一例を示す概略断面図であり、同図では、分離装置３はフロー式カラム型電解合成セルで構成されている。分離装置３は、電極として、カーボン繊維からなる作用電極３１と、白金線からなる対極電極３２を備えている。作用電極３１には、端子３４に接続された電極棒３３を介して電圧が印加される。対極電極３２には、端子３５から電圧が印加される。作用電極３１は、多孔質ガラス管３６の内部に充填されており、対極電極３２は、多孔質ガラス管３６の周囲に巻き付けられている。端子３７には、作用電極３１と対極電極３２に印加される電圧を一定の電位に保つための参照電圧が印加される。 FIG. 3 is a schematic cross-sectional view showing an example of the separation device 3. In FIG. 3, the separation device 3 is composed of a flow column type electrolytic synthesis cell. The separation device 3 includes a working electrode 31 made of carbon fiber and a counter electrode 32 made of platinum wire as electrodes. A voltage is applied to the working electrode 31 via an electrode rod 33 connected to the terminal 34. A voltage is applied to the counter electrode 32 from a terminal 35. The working electrode 31 is filled inside the porous glass tube 36, and the counter electrode 32 is wound around the porous glass tube 36. A reference voltage for keeping the voltage applied to the working electrode 31 and the counter electrode 32 at a constant potential is applied to the terminal 37.
　分離工程Ｓ２では、第１の溶液が導入用パイプ３８を介して多孔質ガラス管３６内に導入され、作用電極３１を通過する。このとき、端子３４および端子３５を介して作用電極３１と対極電極３２との間に所定の電圧を印加することにより、電解反応によって６４Ｃｕのみを作用電極３１に電着させる。これにより、第１の溶液から、ＲＩである６４Ｃｕを分離する。 In the separation step S <b> 2, the first solution is introduced into the porous glass tube 36 through the introduction pipe 38 and passes through the working electrode 31. At this time, by applying a predetermined voltage between the working electrode 31 and the counter electrode 32 via the terminal 34 and the terminal 35, only 64 Cu is electrodeposited on the working electrode 31 by an electrolytic reaction. Thereby, 64 Cu which is RI is separated from the first solution.
　図４は、第１の溶液が１０ｍＭのＨＮＯ３である場合の、Ｎｉ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフであり、図５は、第１の溶液が１００ｍＭのＨＮＯ３である場合の、Ｎｉ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフである。ＣｕとＮｉとでは、標準酸化還元電位（Ｃｕ＋０．３４０Ｖ、Ｎｉ－０．２５７Ｖ）が異なるため、印加電圧に対する電着特性が互いに異なっている。また、金属イオンの印加電圧に対する電着特性は、同一の元素の同位体間で同一である。よって、電極への印加電圧を、Ｎｉ（ＩＩ）の電着率とＣｕ（ＩＩ）の電着率とが異なる電圧とすることにより、６４Ｃｕと６４Ｎｉが溶解した第１の溶液から６４Ｃｕを分離することができる。 FIG. 4 is a graph showing the relationship between the electrodeposition rate of Ni (II) and Cu (II) and the voltage applied to the electrode when the first solution is 10 mM HNO 3 , and FIG. is a graph showing the case where the first solution is HNO 3 in 100 mM, and electrodeposition rate of Ni (II) and Cu (II), the relationship between the applied voltage to the electrode. Since Cu and Ni have different standard oxidation-reduction potentials (Cu + 0.340V, Ni-0.257V), the electrodeposition characteristics with respect to the applied voltage are different from each other. Moreover, the electrodeposition characteristics with respect to the applied voltage of metal ions are the same among isotopes of the same element. Therefore, the voltage applied to the electrodes, by which the electrodeposition rate of Ni (II) electrodeposition rate and Cu (II) is a different voltage, 64 Cu from the first solution 64 Cu and 64 Ni were dissolved Can be separated.
　印加電圧に対する電着特性は、より高い精度でＲＩを分離するという観点から、Ｎｉ（ＩＩ）をＣｕ（ＩＩ）から分離する場合、第１の溶液の種類としてＨＮＯ３やＨＣｌ等の強酸を含む水溶液を用いることが好ましい。第１の溶液の濃度は１０～１００ｍＭに調製することが好ましい。印加電圧は－０．５～－０．１Ｖとすることが好ましく、－０．４～－０．３Ｖとすることが特に好ましい。 The electrodeposition characteristics with respect to the applied voltage include strong acids such as HNO 3 and HCl as the first solution type when separating Ni (II) from Cu (II) from the viewpoint of separating RI with higher accuracy. It is preferable to use an aqueous solution. The concentration of the first solution is preferably adjusted to 10 to 100 mM. The applied voltage is preferably −0.5 to −0.1 V, particularly preferably −0.4 to −0.3 V.
　なお、金属の電着率（％）は、
　（導入用パイプ３８から導入された第１の溶液中の金属の初期濃度－排出用パイプ３９から排出された第１の溶液中の金属濃度）／（導入用パイプ３８から導入された第１の溶液中の金属の初期濃度）×１００
で表わすことができる。 The metal electrodeposition rate (%) is
(Initial concentration of metal in the first solution introduced from the introduction pipe 38-concentration of metal in the first solution discharged from the discharge pipe 39) / (first concentration introduced from the introduction pipe 38) Initial concentration of metal in solution) x 100
It can be expressed as
　（回収）
　続いて、回収工程Ｓ３では、作用電極３１に電着した６４Ｃｕを第２の溶液に溶解させて分離装置３から回収する。本実施形態では、図示しない回収手段により、排出用パイプ３９から第１の溶液を取り出し、その後、導入用パイプ３８から第２の溶液を導入する。第２の溶液としては、ＨＮＯ３やＨＣｌ等の強酸を含む水溶液を用いることができる。第２の溶液に６４Ｃｕを溶解させる際に、作用電極３１に正の電圧を印加することが好ましい。６４Ｃｕが溶解した第２の溶液を排出用パイプ３９から取り出すことにより、６４Ｃｕを分離装置３から回収することができる。 (Recovery)
Subsequently, in the recovery step S3, 64 Cu electrodeposited on the working electrode 31 is dissolved in the second solution and recovered from the separation device 3. In the present embodiment, the first solution is taken out from the discharge pipe 39 by a collecting means (not shown), and then the second solution is introduced from the introduction pipe 38. As the second solution, an aqueous solution containing a strong acid such as HNO 3 or HCl can be used. It is preferable to apply a positive voltage to the working electrode 31 when 64 Cu is dissolved in the second solution. By removing the second solution in which 64 Cu is dissolved from the discharge pipe 39, 64 Cu can be recovered from the separation device 3.
　なお、６４Ｎｉは非常に高価（約５千円／ｍｇ）であるため、排出用パイプ３９から取り出された第１の溶液に溶解している６４Ｎｉは、６４Ｃｕの生成のために再度利用することが好ましい。 Since 64 Ni is very expensive (about 5,000 yen / mg), 64 Ni dissolved in the first solution taken out from the discharge pipe 39 is reused for the production of 64 Cu. It is preferable to do.
　（精製）
　続いて、精製工程Ｓ４では、精製装置４を用いて第２の溶液から６４Ｃｕを精製する。精製装置４は、例えば電気透析型精製装置（ＥＤ）で構成することができる。 (Purification)
Subsequently, in the purification step S4, 64 Cu is purified from the second solution using the purification device 4. The purification device 4 can be constituted by, for example, an electrodialysis purification device (ED).
　図６は、ＥＤで構成された精製装置４の一例を示す概略図である。精製装置４は、陽極チャネル４１、ＡＡ（陰イオンアクセプタ）チャネル４２、ＳＣ（導入チャネル）４３、ＣＡ（陽イオンアクセプタ）チャネル４４および陰極チャネル４５を備えた５層構造であり、陽極チャネル４１および陰極チャネル４５には、それぞれ陽極４６および陰極４７が設けられている。陽極チャネル４１とＡＡチャネル４２は、陽イオン交換膜Ｆ１で隔てられ、ＣＡチャネル４４と陰極チャネル４５は、陰イオン交換膜Ｆ２で隔てられている。ＡＡチャネル４２と導入チャネル４３、および導入チャネル４３とＣＡチャネル４４は、再生セルロース膜Ｆ３で隔てられている。 FIG. 6 is a schematic diagram showing an example of the purification apparatus 4 configured by ED. The purification apparatus 4 has a five-layer structure including an anode channel 41, an AA (anion acceptor) channel 42, an SC (introduction channel) 43, a CA (cation acceptor) channel 44, and a cathode channel 45. The cathode channel 45 is provided with an anode 46 and a cathode 47, respectively. The anode channel 41 and the AA channel 42 are separated by a cation exchange membrane F1, and the CA channel 44 and the cathode channel 45 are separated by an anion exchange membrane F2. The AA channel 42 and the introduction channel 43, and the introduction channel 43 and the CA channel 44 are separated by the regenerated cellulose membrane F3.
　陽極チャネル４１および陰極チャネル４５には、アイソレータが通液される。アイソレータとしては、脱イオン水を用いることができる。ＡＡチャネル４２およびＣＡチャネル４４には、それぞれ陰イオンアクセプタおよび陽イオンアクセプタが通液される。陰イオンアクセプタおよび陽イオンアクセプタとしては、ＨＮＯ３などの強酸や酢酸（ＣＨ３ＣＯ２Ｈ）などの弱酸を用いることができる。導入チャネル４３には、第２の溶液が通液される。 An isolator is passed through the anode channel 41 and the cathode channel 45. As an isolator, deionized water can be used. An anion acceptor and a cation acceptor are passed through the AA channel 42 and the CA channel 44, respectively. As an anion acceptor and a cation acceptor, a strong acid such as HNO 3 or a weak acid such as acetic acid (CH 3 CO 2 H) can be used. The second solution is passed through the introduction channel 43.
　例えば第２の溶液が、６４Ｃｕが溶解したＨＮＯ３溶液である場合、陽極４６と陰極４７との間に電圧を印加することにより、第２の溶液中のＣｕ（ＩＩ）がＮＯ３ －から分離され、ＣＡチャネル４４に泳動される。ＣＡチャネル４４に、後の薬剤合成に適した溶媒（例えば酢酸緩衝液など）を通液すると、標識前駆体と安定に錯形成できる形態（Ｃｕ２＋）で、ＣＡチャネル４４から回収できる。以上のように、精製工程Ｓ４において、第２の溶液から６４Ｃｕを精製することができる。 For example, when the second solution is an HNO 3 solution in which 64 Cu is dissolved, by applying a voltage between the anode 46 and the cathode 47, the Cu (II) in the second solution is changed from NO 3 −. Separate and migrate to CA channel 44. When a solvent (for example, acetate buffer solution) suitable for subsequent drug synthesis is passed through the CA channel 44, it can be recovered from the CA channel 44 in a form (Cu 2+ ) that can be stably complexed with the labeling precursor. As described above, 64 Cu can be purified from the second solution in the purification step S4.
　なお、図６に示す精製装置４では、Ｃｕ（ＩＩ）から分離されたＮＯ３ －はＡＡチャネル４２に移動する。ただし、本発明ではＣｕ（ＩＩ）を回収できればよいため、精製装置４は、ＡＡチャネル４２を備えていない４層構造であってもよい。４層構造の場合は、ＮＯ３ －は導入チャネル４３を素通りする。 In the purification apparatus 4 shown in FIG. 6, NO 3 − separated from Cu (II) moves to the AA channel 42. However, since it is only necessary to recover Cu (II) in the present invention, the purification device 4 may have a four-layer structure that does not include the AA channel 42. In the case of a four-layer structure, NO 3 − passes through the introduction channel 43.
　（薬剤合成）
　その後、６４Ｃｕは、薬剤合成装置に移され、標識前駆体と反応する。これにより、高純度なＣｕ標識薬剤が得られる。なお、Ｃｕ標識薬剤の純度検定は、逆相またはサイズ排除カラムを用いた高速液体クロマトグラフィー（ＨＰＬＣ）により行うことができる。 (Drug synthesis)
The 64 Cu is then transferred to the drug synthesizer and reacts with the labeling precursor. Thereby, a high purity Cu label | marker chemical | medical agent is obtained. The purity test for the Cu-labeled drug can be performed by high performance liquid chromatography (HPLC) using a reverse phase or size exclusion column.
　なお、精製装置４を、電解－電気透析型薬剤合成装置（ＥＤＳ）で構成することにより、精製工程Ｓ４において薬剤合成も可能となる。具体的には、図６に示すＣＡチャネル４４に標識前駆体を導入することにより、ＣＡチャネル４４に移動したＣｕ（ＩＩ）（主にＣｕ２＋）が標識前駆体と反応し、Ｃｕ標識薬剤が得られる。 It should be noted that by synthesizing the purification device 4 with an electro-electrodialysis type drug synthesizer (EDS), drug synthesis can be performed in the purification step S4. Specifically, by introducing a labeled precursor into the CA channel 44 shown in FIG. 6, Cu (II) (mainly Cu 2+ ) moved to the CA channel 44 reacts with the labeled precursor, and the Cu-labeled drug is can get.
　〔本実施形態の効果〕
　本実施形態における各工程での所要時間について、照射工程Ｓ１は約２時間であり、従来技術における照射工程Ｓ１０１（図１１）と同じであるが、分離工程Ｓ２および回収工程Ｓ３は約５分であり、精製工程Ｓ４も約５分である。すなわち、分離工程Ｓ２～Ｓ４の所要時間は約１０分程度であり、従来技術における置換工程Ｓ１０２～精製工程Ｓ１０４の所要時間（約３時間３０分）に比べ、大幅に時間を短縮することができる。よって、本実施形態では、短時間にＲＩを分離・精製することができ、放射性薬剤を取り扱うための厳しい時間的制約を解消することができる。 [Effect of this embodiment]
Regarding the time required for each step in this embodiment, the irradiation step S1 is about 2 hours, which is the same as the irradiation step S101 (FIG. 11) in the prior art, but the separation step S2 and the recovery step S3 are about 5 minutes. Yes, the purification step S4 is also about 5 minutes. That is, the time required for the separation steps S2 to S4 is about 10 minutes, and the time can be significantly shortened compared to the time required for the replacement step S102 to the purification step S104 (about 3 hours 30 minutes) in the prior art. . Therefore, in this embodiment, RI can be separated and purified in a short time, and severe time restrictions for handling radiopharmaceuticals can be eliminated.
　また、薬剤合成に使用されるＲＩの製造量は少量であるため、精製工程Ｓ４において用いられる精製装置４の各チャネルでの通液量が少なくて済む。そのため、精製装置４の小型化は容易であり、本実施形態に係る精製装置４は、縦１１ｃｍ×横３ｃｍ×高さ２．５ｃｍ程度のサイズである。よって、ＲＩ分離精製システム２０の規模を小さくすることができ、医療現場での空間的制限の解消にも貢献することができる。 Further, since the production amount of RI used for drug synthesis is small, the amount of liquid passing through each channel of the purification apparatus 4 used in the purification step S4 can be small. For this reason, the refining device 4 can be easily downsized, and the refining device 4 according to the present embodiment has a size of about 11 cm long × 3 cm wide × 2.5 cm high. Therefore, the scale of the RI separation and purification system 20 can be reduced, and it is possible to contribute to the elimination of spatial restrictions at the medical site.
　また、照射工程によって生成する６４Ｃｕは，サブｎｍｏｌレベルであるため、従来技術の置換工程Ｓ１０２～精製工程Ｓ１０４において用いられる装置は、６４Ｃｕをハンドリングするには規模が大きく、精製によるロスや反応効率低下が生じていた。これに対し、本実施形態では、６４Ｃｕの生成量に合わせてシステム規模を小型化することにより、高効率にＲＩを分離精製することができる。 In addition, since 64 Cu generated by the irradiation process is at a sub nmol level, the apparatus used in the substitution process S102 to the purification process S104 of the prior art has a large scale for handling 64 Cu, and loss and reaction due to purification. There was a drop in efficiency. In contrast, in the present embodiment, RI can be separated and purified with high efficiency by reducing the system scale according to the amount of 64 Cu produced.
　なお、ＲＩ製造システム１００では、照射装置１０と分離装置３、および、分離装置３と精製装置４がシームレスに接続されていることが好ましい。これにより、図２に示す照射工程Ｓ１～精製工程Ｓ４を連続的に実施することができ、さらに迅速にＲＩを分離精製することができる。 In the RI manufacturing system 100, it is preferable that the irradiation device 10 and the separation device 3 and the separation device 3 and the purification device 4 are seamlessly connected. Thereby, the irradiation step S1 to the purification step S4 shown in FIG. 2 can be carried out continuously, and RI can be further separated and purified.
　〔付記事項〕
　以上、本発明の実施形態について説明したが、本発明は上記実施形態に限定されるものではなく、その趣旨を逸脱しない限りにおいて、種々の変更が可能である。 [Additional Notes]
Although the embodiments of the present invention have been described above, the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the spirit of the present invention.
　例えば、上記実施形態では、金属およびＲＩがそれぞれ６４Ｎｉおよび６４Ｃｕであったが、本発明はこれに限定されない。溶液への印加電圧に対する電極への電着特性（標準酸化還元電位）が、ＲＩと異なる金属であれば本発明に適用可能である。例えば、金属がＮｉあるいはＺｎであって、ＲＩがＣｕの組み合わせが挙げられる。具体的には、そのような金属およびＲＩとして、６３Ｃｕおよび６６Ｇa（標準酸化還元電位－０．５２９Ｖ）、６７Ｚｎ（標準酸化還元電位－０．７６３Ｖ）および６７Ｃｕ、並びに６８Ｚｎ（標準酸化還元電位－０．７６３Ｖ）および６７Ｃｕが挙げられる。６６Ｇaは、半減期が９．４時間であり、陽電子を放出するため、ＰＥＴ診断に有用である。６７Ｃｕは、半減期が６１．８時間であり、β線を放出するため、がんの内用療法に有用である。 For example, in the above embodiment, the metal and RI were 64 Ni and 64 Cu, respectively, but the present invention is not limited to this. Any electrodeposition characteristic (standard oxidation-reduction potential) to the electrode with respect to the voltage applied to the solution can be applied to the present invention as long as the metal is different from RI. For example, there is a combination in which the metal is Ni or Zn and the RI is Cu. Specifically, as such metals and RI, 63 Cu and 66 Ga (standard redox potential -0.529 V), 67 Zn (standard redox potential -0.763 V) and 67 Cu, and 68 Zn (standard Redox potential -0.763 V) and 67 Cu. 66 Ga is useful for PET diagnosis because it has a half-life of 9.4 hours and emits positrons. Since 67 Cu has a half-life of 61.8 hours and emits β rays, it is useful for internal therapy of cancer.
　図７は、１００ｍＭのＨＮＯ３溶液に溶解したＺｎ（ＩＩ）およびＣｕ（ＩＩ）の電着率と、電極への印加電圧との関係を示すグラフである。ＣｕとＺｎとでは、標準酸化還元電位が異なるため、印加電圧に対する電着特性が互いに異なっている。よって、電極への印加電圧を、Ｚｎ（ＩＩ）の電着率とＣｕ（ＩＩ）の電着率とが異なる電圧とすることにより、６７Ｃｕと６７Ｚｎまたは６７Ｃｕと６８Ｚｎが溶解した第１の溶液から６７Ｃｕを分離することができる。 FIG. 7 is a graph showing the relationship between the electrodeposition rates of Zn (II) and Cu (II) dissolved in a 100 mM HNO 3 solution and the voltage applied to the electrodes. Since Cu and Zn have different standard redox potentials, the electrodeposition characteristics with respect to the applied voltage are different from each other. Therefore, the voltage applied to the electrode is such that the electrodeposition rate of Zn (II) and the electrodeposition rate of Cu (II) are different, so that 67 Cu and 67 Zn or 67 Cu and 68 Zn are dissolved. 67 Cu can be separated from one solution.
　なお、金属の電着率とＲＩの電着率との差が大きいほど（すなわちどちらかの電着率が０％か１００％に近いほど）、効率的にＲＩを分離することができるが、両者の差があまり大きくない場合であっても、分離装置３内で第１の溶液を循環させることにより、ＲＩの回収率を高めることができる。 The larger the difference between the electrodeposition rate of metal and the electrodeposition rate of RI (that is, the closer one of electrodeposition rates is to 0% or 100%), the more efficiently RI can be separated. Even if the difference between the two is not so large, the recovery rate of RI can be increased by circulating the first solution in the separation device 3.
　以下、本発明の実施例について説明するが、本発明は下記の実施例に限定されない。 Examples of the present invention will be described below, but the present invention is not limited to the following examples.
　〔実施例１〕
　実施例１では、上記実施形態に係る分離装置３を用いて、Ｎｉ（ＩＩ）とＣｕ（ＩＩ）とを含む第１の溶液からＣｕ（ＩＩ）を分離する実験を行った。 [Example 1]
In Example 1, an experiment for separating Cu (II) from a first solution containing Ni (II) and Cu (II) was performed using the separation device 3 according to the above embodiment.
　（実験条件）
　分離装置３は、北斗電工株式会社製のカラム型電解合成セル（電解合成・分析用カラム型フローセルＨＸ－２０１）を用いた。なお、本製品の詳細は、特開２０００－１１９８８５号公報に開示されている。 (Experimental conditions)
As the separation apparatus 3, a column type electrolytic synthesis cell (electrolytic synthesis / analysis column type flow cell HX-201) manufactured by Hokuto Denko Co., Ltd. was used. Details of this product are disclosed in Japanese Patent Application Laid-Open No. 2000-119885.
　第１の溶液としては、６．０μＭのＮｉ（ＩＩ）と６．０μＭのＣｕ（ＩＩ）とを１００ｍＭのＨＮＯ３溶液に溶解させた溶液と、１０ｍＭのＨＮＯ３溶液に溶解させた溶液との２つを用意した。第１の溶液を分離装置３の導入用パイプ３８を介して多孔質ガラス管３６内に導入した。第１の溶液の流量は、１．０ｍＬ／ｍｉｎであった。第１の溶液を多孔質ガラス管３６に通液した状態で、電極３１，３２間に電圧を印加し、第１の溶液を排出用パイプ３９から取り出した。その後、作用電極３１に電着した金属を溶離させるための第２の溶液を多孔質ガラス管３６内に通液しながら、電極３１，３２間に０．５Ｖの電圧を印加し、第２の溶液を排出用パイプ３９から取り出した。第１の溶液の通液を一回行う度に、印加電圧を－０．８～＋０．８Ｖの範囲で０．１Ｖずつ切り替えた。第２の溶液は、１０ｍＭおよび１００ｍＭのＨＮＯ３溶液を用いた。分離装置３から取り出された第２の溶液中の金属イオンの測定を、原子吸光光度計（ＡＡＳ）によって行った。 As the first solution, a solution prepared by dissolving 6.0 μM Ni (II) and 6.0 μM Cu (II) in a 100 mM HNO 3 solution and a solution dissolved in a 10 mM HNO 3 solution are used. Two were prepared. The first solution was introduced into the porous glass tube 36 through the introduction pipe 38 of the separation device 3. The flow rate of the first solution was 1.0 mL / min. In a state where the first solution was passed through the porous glass tube 36, a voltage was applied between the electrodes 31 and 32, and the first solution was taken out from the discharge pipe 39. Thereafter, while passing a second solution for eluting the metal electrodeposited on the working electrode 31 through the porous glass tube 36, a voltage of 0.5 V is applied between the electrodes 31 and 32, and the second solution The solution was taken out from the discharge pipe 39. Each time the first solution was passed, the applied voltage was switched by 0.1 V in the range of −0.8 to +0.8 V. As the second solution, 10 mM and 100 mM HNO 3 solutions were used. Measurement of metal ions in the second solution taken out from the separation device 3 was performed by an atomic absorption photometer (AAS).
　（結果）
　図８は、第１の溶液として１００ｍＭのＨＮＯ３溶液および１０ｍＭのＨＮＯ３を用いた場合の、Ｃｕ（ＩＩ）の回収率と電着時の印加電圧との関係を示すグラフである。第１の溶液として１００ｍＭのＨＮＯ３溶液を用いた場合、印加電圧を－０．５～－０．２Ｖとすることにより、回収率が非常に高くなった。第１の溶液として１０ｍＭのＨＮＯ３溶液を用いた場合、印加電圧を－０．５～－０．３Ｖとすることにより、回収率が非常に高くなった。実施例１では、一般試薬すなわち天然組成のＮｉおよびＣｕ（以下、ｎａｔＮｉおよびｎａｔＣｕ）を用いたが、溶解した金属イオンの印加電圧に対する電着特性は、同一の元素の同位体間で同一である。すなわち、ｎａｔＮｉ（ＩＩ）と６４Ｎｉ（ＩＩ）（主にｎａｔＮｉ２＋と６４Ｎｉ２＋）の電着特性は同一であり、ｎａｔＣｕ（ＩＩ）と６４Ｃｕ（ＩＩ）（主にｎａｔＣｕ２＋と６４Ｃｕ２＋）の電着特性は同一である。よって、分離装置３を用いることにより、６４Ｎｉおよび６４Ｃｕを含む第１の溶液から６４Ｃｕを高効率に分離できることが分かった。 (result)
FIG. 8 is a graph showing the relationship between the recovery rate of Cu (II) and the applied voltage during electrodeposition when a 100 mM HNO 3 solution and 10 mM HNO 3 are used as the first solution. When a 100 mM HNO 3 solution was used as the first solution, the recovery rate was very high by setting the applied voltage to −0.5 to −0.2V. When a 10 mM HNO 3 solution was used as the first solution, the recovery rate became very high when the applied voltage was -0.5 to -0.3 V. In Example 1, general reagents, ie, Ni and Cu of natural composition (hereinafter referred to as natNi and natCu) were used, but the electrodeposition characteristics of dissolved metal ions with respect to the applied voltage are the same between isotopes of the same element. . That is, the electrodeposition characteristics of nat Ni (II) and 64 Ni (II) (mainly nat Ni 2+ and 64 Ni 2+ ) are the same, and nat Cu (II) and 64 Cu (II) (mainly nat Cu 2+ And 64 Cu 2+ ) have the same electrodeposition characteristics. Therefore, it was found that 64 Cu can be separated with high efficiency from the first solution containing 64 Ni and 64 Cu by using the separation device 3.
　なお、回収率（％）は、
　（回収工程で排出用パイプ３９から排出された第２の溶液中のＣｕ（ＩＩ）濃度）／（分離工程で導入用パイプ３８から導入された第１の溶液中のＣｕ（ＩＩ）初期濃度）×１００
で算出している。そのため、Ｃｕ（ＩＩ）が濃縮された状態で回収された場合、回収率が１００％を超えることとなる。 The recovery rate (%) is
(Cu (II) concentration in the second solution discharged from the discharge pipe 39 in the recovery step) / (Cu (II) initial concentration in the first solution introduced from the introduction pipe 38 in the separation step)) × 100
It is calculated by. Therefore, when Cu (II) is recovered in a concentrated state, the recovery rate exceeds 100%.
　〔実施例２〕
　実施例２では、上記実施形態に係る精製装置４を用いて、第２の溶液からＣｕを精製する実験を行った。 [Example 2]
In Example 2, an experiment for purifying Cu from the second solution was performed using the purification apparatus 4 according to the above embodiment.
　（実験条件）
　精製装置４として、図６に示す５層構造の電気透析型精製装置を用いた。陽極チャネル４１および陰極チャネル４５には、アイソレータとして脱イオン水を通液し、ＡＡチャネル４２およびＣＡチャネル４４には、アクセプター溶液として１０ｍＭのＨＮＯ３溶液またはＣＨ３ＣＯ２Ｈ溶液を通液し、導入チャネル４３には第２の溶液を通液した。第２の溶液は、５．０μＭのＣｕ（ＩＩ）（主にＣｕ２＋の形態として）を溶解したＨＮＯ３溶液を用いた。５つのチャネル４１～４５に通液しながら、電極４６，４７間に電圧を印加し、チャネル４２，４３，４４からそれぞれ溶出液ＡＡ，ＳＣ，ＣＡを取り出した。チャネル４１～４５における流速は、いずれも０．３ｍＬ／ｍｉｎであり、印加電圧は、０～３５Ｖの範囲で溶出液を取り出す毎に５Ｖずつ切り替えた。取り出した溶出液ＡＡ，ＳＣ，ＣＡにおけるＣｕ（ＩＩ）の濃度を計測することにより、Ｃｕ（ＩＩ）の抽出率を算出した。 (Experimental conditions)
As the purification device 4, an electrodialysis purification device having a five-layer structure shown in FIG. 6 was used. Deionized water is passed through the anode channel 41 and the cathode channel 45 as an isolator, and a 10 mM HNO 3 solution or CH 3 CO 2 H solution is passed through the AA channel 42 and the CA channel 44 as an acceptor solution, The second solution was passed through the introduction channel 43. As the second solution, an HNO 3 solution in which 5.0 μM Cu (II) (mainly in the form of Cu 2+ ) was dissolved was used. While passing through the five channels 41 to 45, a voltage was applied between the electrodes 46 and 47, and the eluates AA, SC and CA were taken out from the channels 42, 43 and 44, respectively. The flow rates in the channels 41 to 45 were all 0.3 mL / min, and the applied voltage was switched by 5 V each time the eluate was taken out in the range of 0 to 35 V. The extraction ratio of Cu (II) was calculated by measuring the concentration of Cu (II) in the extracted eluates AA, SC, CA.
　なお、抽出率（％）は、
　（チャネル４３に導入された溶液中の金属濃度－各チャネル４２，４３，４４から溶出された溶液中の金属濃度）／（チャネル４３に導入された溶液中の金属濃度）×１００
で表わすことができる。 The extraction rate (%) is
(Metal concentration in solution introduced into channel 43−metal concentration in solution eluted from each channel 42, 43, 44) / (metal concentration in solution introduced into channel 43) × 100
It can be expressed as
　（結果）
　図９（ａ）～（ｃ）はそれぞれ、アクセプター溶液として１０ｍＭのＨＮＯ３溶液を用いた場合の、溶出液ＡＡ，ＳＣ，ＣＡにおけるＣｕ（ＩＩ）の抽出率と電極４６，４７間への印加電圧との関係を示すグラフである。この場合、印加電圧を高くするほど、チャネル４４からの溶出液ＣＡからＣｕ（ＩＩ）を高効率に抽出できることが分かった。 (result)
FIGS. 9A to 9C show the extraction rate of Cu (II) in the eluents AA, SC, and CA and the application between the electrodes 46 and 47, respectively, when a 10 mM HNO 3 solution is used as the acceptor solution. It is a graph which shows the relationship with a voltage. In this case, it was found that Cu (II) can be extracted from the eluent CA from the channel 44 with higher efficiency as the applied voltage is increased.
　図１０（ａ）～（ｃ）はそれぞれ、アクセプター溶液として１０ｍＭのＣＨ３ＣＯ２Ｈ溶液を用いた場合の、溶出液ＡＡ，ＳＣ，ＣＡにおけるＣｕ（ＩＩ）の抽出率と電極４６，４７間への印加電圧との関係を示すグラフである。この場合、印加電圧を５～１０Ｖとすることにより、１００％に近い抽出率を達成できた。 10 (a) to 10 (c) show the extraction ratio of Cu (II) in the eluate AA, SC, CA and the distance between the electrodes 46, 47 when a 10 mM CH 3 CO 2 H solution is used as the acceptor solution. It is a graph which shows the relationship with the applied voltage to. In this case, an extraction rate close to 100% could be achieved by setting the applied voltage to 5 to 10V.
　なお実施例２では、検出器（原子吸光）の定量下限値に併せてＣｕ（ＩＩ）の濃度を調製したが、この濃度をさらに低濃度にすると塩基性でも溶解するので、さらに広い範囲での印加電圧でＣｕ（ＩＩ）の精製が可能であると考えられる。 In Example 2, the concentration of Cu (II) was adjusted in accordance with the lower limit of quantification of the detector (atomic absorption). However, if this concentration is further reduced, it dissolves even in basic, so in a wider range. It is considered that Cu (II) can be purified with an applied voltage.
　〔実施例３〕
　実施例３では、上記実施形態に係る分離装置３を用いて、５７Ｎｉ（ＩＩ）と６４Ｃｕ（ＩＩ）とを含む第１の溶液から６４Ｃｕ（ＩＩ）を分離する実験を行った。 Example 3
In Example 3, an experiment for separating 64 Cu (II) from a first solution containing 57 Ni (II) and 64 Cu (II) was performed using the separation apparatus 3 according to the above embodiment.
　（実験条件）
　分離装置３は、実施例１と同様、北斗電工株式会社製のカラム型電解合成セル（電解合成・分析用カラム型フローセルＨＸ－２０１）を用いた。 (Experimental conditions)
As the separator 3, a column type electrolytic synthesis cell (electrolytic synthesis / analysis column type flow cell HX-201) manufactured by Hokuto Denko Co., Ltd. was used as in Example 1.
　第１の溶液としては、酸化ニッケルへの陽子ビーム照射により得られた５７Ｎｉ（ＩＩ）と６４Ｃｕ（ＩＩ）とを５ｍＬの１００ｍＭのＨＣｌ溶液に溶解させた溶液を用意した。第１の溶液を分離装置３の導入用パイプ３８を介して多孔質ガラス管３６内に導入した。第１の溶液を多孔質ガラス管３６に通液した状態で、電極３１，３２間に－０．６Ｖの電圧を印加し、排出用パイプ３９から溶液を２ｍＬずつ５回に分けて取り出した。 As the first solution, a solution prepared by dissolving 57 Ni (II) and 64 Cu (II) obtained by proton beam irradiation on nickel oxide in 5 mL of 100 mM HCl solution was prepared. The first solution was introduced into the porous glass tube 36 through the introduction pipe 38 of the separation device 3. In a state where the first solution was passed through the porous glass tube 36, a voltage of −0.6 V was applied between the electrodes 31 and 32, and the solution was taken out from the discharge pipe 39 in two portions of 2 mL.
　その後、第１の溶液を洗浄するため、第２の溶液を多孔質ガラス管３６内に通液し、排出用パイプ３９から溶液を２ｍＬずつ２回に分けて取り出した。さらに、作用電極３１に電着した６４Ｃｕを溶離させるため、電極３１，３２間に印加する電圧を－０．６Ｖから＋０．６Ｖに切り替えて、第２の溶液を多孔質ガラス管３６内に通液しながら、排出用パイプ３９から溶液を２ｍＬずつ４回に分けて取り出した。第２の溶液は、１００ｍＭのＨＮＯ３溶液を用いた。 Thereafter, in order to wash the first solution, the second solution was passed through the porous glass tube 36, and the solution was taken out from the discharge pipe 39 in 2 mL portions in two portions. Further, in order to elute 64 Cu electrodeposited on the working electrode 31, the voltage applied between the electrodes 31 and 32 is switched from -0.6V to + 0.6V, and the second solution is put into the porous glass tube 36. While passing through the solution, the solution was taken out from the discharge pipe 39 in two portions of 2 mL. As the second solution, a 100 mM HNO 3 solution was used.
　このようにして、排出用パイプ３９から計１１回取り出された溶液について、溶液中の金属イオンの測定を、ＮａＩウェル検出器およびＧｅ検出器で測定した。 Thus, for the solution taken out from the discharge pipe 39 a total of 11 times, the measurement of metal ions in the solution was measured with a NaI well detector and a Ge detector.
　（結果）
　図１２は、排出用パイプ３９から取り出された溶液中の５７Ｎｉ（ＩＩ）および６４Ｃｕ（ＩＩ）の濃度を示すグラフである。横軸は、溶液の取り出された順番を示している。－０．６Ｖの電圧印加により、第１の溶液の６４Ｃｕ（ＩＩ）は作用電極３１に電着するため、１～４回目に取り出された溶液では、ほぼ５７Ｎｉ（ＩＩ）のみが検出された。なお、１回目に取り出された溶液では、第１の溶液を導入する前に分析装置３に存在していた溶液の割合が高いため、５７Ｎｉ（ＩＩ）の濃度が低くなっている。第１の溶液に導入された第１の溶液は計５ｍＬであるため、５７Ｎｉ（ＩＩ）の濃度は、２回目に取り出された溶液で最大になった後、徐々に低下し、５回目には取り出された溶液では、ほとんど検出されなくなった。 (result)
FIG. 12 is a graph showing the concentrations of 57 Ni (II) and 64 Cu (II) in the solution taken out from the discharge pipe 39. The horizontal axis indicates the order in which the solutions are removed. When a voltage of −0.6 V is applied, 64 Cu (II) of the first solution is electrodeposited on the working electrode 31, so only about 57 Ni (II) is detected in the solution taken out the first to fourth times. It was. In the solution taken out for the first time, the concentration of 57 Ni (II) is low because the ratio of the solution present in the analyzer 3 before introducing the first solution is high. Since the total amount of the first solution introduced into the first solution is 5 mL, the concentration of 57 Ni (II) reaches a maximum with the solution taken out for the second time and then gradually decreases. Was hardly detected in the removed solution.
　６～７回目に取り出された溶液（第１の溶液と第２の溶液との混合溶液）では、溶離用の電圧が印加されていないため、Ｎｉ（ＩＩ）および６４Ｃｕ（ＩＩ）はいずれも検出されなかった。 In the solution taken out 6 to 7 times (mixed solution of the first solution and the second solution), no voltage for elution is applied, so both Ni (II) and 64 Cu (II) Not detected.
　その後、印加電圧が＋０．６Ｖに切り替えられることにより、作用電極３１に電着した６４Ｃｕ（０価）が溶離するため、８～１１回目に取り出された溶液（第２の溶液）では、ほぼ６４Ｃｕ（ＩＩ）のみが検出された。 Thereafter, by switching the applied voltage to +0.6 V, 64 Cu (zero valence) electrodeposited on the working electrode 31 elutes, so that the solution taken out for the eighth to eleventh times (second solution) is almost Only 64 Cu (II) was detected.
　〔実施例４〕
　実施例４では、上記実施形態に係る精製装置４を用いて、第２の溶液から６４Ｃｕ（ＩＩ）を精製する実験を行った。 Example 4
In Example 4, an experiment for purifying 64 Cu (II) from the second solution was performed using the purification apparatus 4 according to the above embodiment.
　（実験条件）
　精製装置４として、実施例２と同様、図６に示す５層構造の電気透析型精製装置を用いた。前工程として、全チャネル４１～４５に脱イオン水を通液した後、電極４６，４７間に１５Ｖの電圧を印加した、その後、陽極チャネル４１および陰極チャネル４５には、アイソレータとして純水を通液し、ＡＡチャネル４２およびＣＡチャネル４４には、アクセプター溶液として１０ｍＭのＣＨ３ＣＯ２Ｈ溶液を通液し、導入チャネル４３には第２の溶液を通液した。第２の溶液は、６４Ｃｕ（ＩＩ）が溶解した１０ｍＭのＨＣｌ溶液を用いた。５つのチャネル４１～４５に通液しながら、電極４６，４７間に１５Ｖの電圧を印加し、チャネル４２，４３，４４からそれぞれ溶出液ＡＡ，ＳＣ，ＣＡを１．５ｍＬずつ計３回取り出した。チャネル４１～４５における流速は、いずれも０．３ｍＬ／ｍｉｎであった。 (Experimental conditions)
As the purification apparatus 4, the electrodialysis purification apparatus having a five-layer structure shown in FIG. As a pre-process, after deionized water is passed through all the channels 41 to 45, a voltage of 15 V is applied between the electrodes 46 and 47, and then pure water is passed through the anode channel 41 and the cathode channel 45 as an isolator. A 10 mM CH 3 CO 2 H solution was passed as an acceptor solution through the AA channel 42 and the CA channel 44, and a second solution was passed through the introduction channel 43. As the second solution, a 10 mM HCl solution in which 64 Cu (II) was dissolved was used. While passing through the five channels 41 to 45, a voltage of 15 V was applied between the electrodes 46 and 47, and 1.5 mL of the eluate AA, SC, CA was taken out from the channels 42, 43, and 44, respectively, for a total of three times. . The flow rates in the channels 41 to 45 were all 0.3 mL / min.
　その後、チャネル４２，４３，４４からそれぞれ溶出液ＡＡ，ＳＣ，ＣＡを１．５ｍＬずつ計３回取り出した。計６回取り出した溶出液ＡＡ，ＳＣ，ＣＡにおける６４Ｃｕ（ＩＩ）の濃度を計測することにより、６４Ｃｕ（ＩＩ）の抽出率を算出した。抽出率の計算式は、実施例２と同様である。また、精製装置４を通過した後の、他の金属元素の含有量を、ＩＣＰ－ＡＥＳを用いて測定した。 Thereafter, 1.5 mL each of the eluates AA, SC, and CA was taken out from the channels 42, 43, and 44, for a total of three times. The extraction ratio of 64 Cu (II) was calculated by measuring the concentration of 64 Cu (II) in the eluates AA, SC, CA taken out a total of 6 times. The calculation formula for the extraction rate is the same as that in the second embodiment. Further, the content of other metal elements after passing through the purification apparatus 4 was measured using ICP-AES.
　（結果）
　図１３（ａ）～（ｃ）はそれぞれ、溶出液ＡＡ，ＳＣ，ＣＡにおける６４Ｃｕ（ＩＩ）の抽出率を示すグラフである。横軸は、溶液の取り出された順番を示している。１～３回目に取り出された溶出液ＣＡでは、１０～２０％の抽出率となっているが、これは、６４Ｃｕ（ＩＩ）がＣＡチャネル４４に吸着するためであると考えられる。その後、４回目に取り出された溶出液ＣＡでは、抽出率が１００％を超えているが、これは、導入チャネル４３にＨＣｌを通液することにより、Ｈ＋がＣＡチャネル４４に移動して、ＣＡチャネル４４内のｐＨが下がり、ＣＡチャネル４４に吸着していた６４Ｃｕ（ＩＩ）が溶解したためと考えられる。 (result)
FIGS. 13A to 13C are graphs showing the extraction rate of 64 Cu (II) in the eluents AA, SC, and CA, respectively. The horizontal axis indicates the order in which the solutions are removed. The eluate CA taken out for the first to third times has an extraction rate of 10 to 20%, which is considered to be due to adsorption of 64 Cu (II) to the CA channel 44. Thereafter, in the eluate CA taken out for the fourth time, the extraction rate exceeds 100%. This is because H + moves to the CA channel 44 by passing HCl through the introduction channel 43, This is probably because the pH in the CA channel 44 dropped and 64 Cu (II) adsorbed on the CA channel 44 was dissolved.
　図１４は、精製装置４を通過した後の、ＮｉおよびＣｕ以外の金属元素の含有量を示す表である。単位はｍｇ／Ｌであり、「－」は、含有量が検出限界以下であることを示している。また、「＜０．００１」または「＜０．００２」は、定量下限値以下であることを示している。図１４に示す各数値は、臨床で問題ないレベルである。 FIG. 14 is a table showing the contents of metal elements other than Ni and Cu after passing through the purification apparatus 4. The unit is mg / L, and “−” indicates that the content is below the detection limit. Further, “<0.001” or “<0.002” indicates that the value is below the lower limit of quantification. Each numerical value shown in FIG. 14 is a level at which there is no problem in clinical practice.
　図１４に示す金属は、酸化ニッケルや大気に含まれており、放射性金属の製造工程において第１および第２の溶液に混入することは避けられないが、精製装置４によってこれらの金属が取り除かれていることが分かった。 The metals shown in FIG. 14 are contained in nickel oxide and air, and are inevitably mixed into the first and second solutions in the manufacturing process of radioactive metals, but these metals are removed by the purifier 4. I found out.
１　　　サイクロトロン
２　　　照射用金属
３　　　分離装置
４　　　精製装置
１０　　照射装置
２０　　ＲＩ分離精製システム
３１　　作用電極
３２　　対極電極
３３　　電極棒
３４　　端子
３５　　端子
３６　　多孔質ガラス管
３７　　端子
３８　　導入用パイプ
３９　　排出用パイプ
４１　　陽極チャネル
４２　　ＡＡチャネル
４３　　導入チャネル
４４　　ＣＡチャネル
４５　　陰極チャネル
４６　　陽極
４７　　陰極
１００　ＲＩ製造システム
Ｆ１　　陽イオン交換膜
Ｆ２　　陰イオン交換膜
Ｆ３　　再生セルロース膜
Ｓ１　　照射工程
Ｓ２　　分離工程
Ｓ３　　回収工程
Ｓ４　　精製工程 DESCRIPTION OF SYMBOLS 1 Cyclotron 2 Metal for irradiation 3 Separation apparatus 4 Purification apparatus 10 Irradiation apparatus 20 RI separation and purification system 31 Working electrode 32 Counter electrode 33 Electrode rod 34 Terminal 35 Terminal 36 Porous glass tube 37 Terminal 38 Introduction pipe 39 Discharge pipe 41 Anode Channel 42 AA channel 43 Introduction channel 44 CA channel 45 Cathode channel 46 Anode 47 Cathode 100 RI production system F1 Cation exchange membrane F2 Anion exchange membrane F3 Regenerated cellulose membrane S1 Irradiation step S2 Separation step S3 Recovery step S4 Purification step

Claims (10)

  1. 　金属と当該金属から変換されてなる放射性同位体（ＲＩ）とを含む第１の溶液から前記ＲＩを分離する分離装置であって、
    　前記第１の溶液に所定の電圧を印加するための電極を備え、
    　前記所定の電圧は、前記金属の前記電極への電着率と前記ＲＩの前記電極への電着率とが異なる電圧である、分離装置。     A separation device for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal,
    An electrode for applying a predetermined voltage to the first solution;
    The separation apparatus, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
  2. 　前記金属はＮｉであり、前記ＲＩはＣｕである、請求項１に記載の分離装置。 The separation device according to claim 1, wherein the metal is Ni and the RI is Cu.
  3. 　前記金属はＺｎであり、前記ＲＩはＣｕである、請求項１に記載の分離装置。 The separation apparatus according to claim 1, wherein the metal is Zn, and the RI is Cu.
  4. 　前記電極に電着した前記ＲＩを第２の溶液に溶解させて前記分離装置から回収する回収手段をさらに備える、請求項１～３のいずれかに記載の分離装置。 The separation apparatus according to any one of claims 1 to 3, further comprising recovery means for dissolving the RI electrodeposited on the electrode in the second solution and recovering the RI from the separation apparatus.
  5. 　請求項４に記載の分離装置と、
    　前記第２の溶液から前記ＲＩを精製する精製装置と、
    を備えた、ＲＩ分離精製システム。     A separation device according to claim 4;
    A purification device for purifying the RI from the second solution;
    RI separation and purification system.
  6. 　金属と当該金属から変換されてなる放射性同位体（ＲＩ）とを含む第１の溶液から前記ＲＩを分離する分離方法であって、
    　電極を介して前記第１の溶液に所定の電圧を印加する印加工程を備え、
    　前記所定の電圧は、前記金属の前記電極への電着率と前記ＲＩの前記電極への電着率とが異なる電圧である、分離方法。     A separation method for separating RI from a first solution containing a metal and a radioisotope (RI) converted from the metal,
    An application step of applying a predetermined voltage to the first solution via an electrode;
    The separation method, wherein the predetermined voltage is a voltage in which an electrodeposition rate of the metal to the electrode and an electrodeposition rate of the RI to the electrode are different.
  7. 　前記金属はＮｉであり、前記ＲＩはＣｕである、請求項６に記載の分離方法。 The separation method according to claim 6, wherein the metal is Ni and the RI is Cu.
  8. 　前記金属はＺｎであり、前記ＲＩはＣｕである、請求項６に記載の分離方法。 The separation method according to claim 6, wherein the metal is Zn and the RI is Cu.
  9. 　前記電極に電着した前記ＲＩを第２の溶液に溶解させて前記分離装置から回収する回収工程をさらに備える、請求項６～８のいずれかに記載の分離方法。 The separation method according to any one of claims 6 to 8, further comprising a recovery step of dissolving the RI electrodeposited on the electrode in the second solution and recovering it from the separation device.
  10. 　請求項９に記載の分離方法の各工程と、
    　前記第２の溶液から前記ＲＩを精製する精製工程と、
    を備えた、ＲＩ分離精製方法。     Each step of the separation method according to claim 9,
    A purification step of purifying the RI from the second solution;
    RI separation and purification method comprising:
PCT/JP2019/016800 2018-04-19 2019-04-19 Separating device, separating method, ri separation and purification system, and ri separation and purification method WO2019203342A1 (en)

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US11521762B2 (en) 2020-09-03 2022-12-06 Curium Us Llc Purification process for the preparation of non-carrier added copper-64
US11972874B2 (en) 2023-06-22 2024-04-30 Curium Us Llc Purification process for the preparation of non-carrier added copper-64

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JP5880931B2 (en) * 2011-11-30 2016-03-09 住友重機械工業株式会社 64Cu separation and purification method and 64Cu separation and purification apparatus

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US3491003A (en) * 1967-07-07 1970-01-20 Atomic Energy Commission Method of separating polonium from irradiated bismuth
JP2014535043A (en) * 2011-09-29 2014-12-25 ユーシカゴ・アーゴン・リミテッド・ライアビリティ・カンパニーＵＣｈｉｃａｇｏ Ａｒｇｏｎｎｅ， ＬＬＣ Method for producing Cu-67 radioisotope using ceramic capsule for medical use
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Publication number Priority date Publication date Assignee Title
US11521762B2 (en) 2020-09-03 2022-12-06 Curium Us Llc Purification process for the preparation of non-carrier added copper-64
US11581103B2 (en) 2020-09-03 2023-02-14 Curium Us Llc Purification process for the preparation of non-carrier added copper-64
US11798701B2 (en) 2020-09-03 2023-10-24 Curium Us Llc Purification process for the preparation of non-carrier added copper-64
US11972874B2 (en) 2023-06-22 2024-04-30 Curium Us Llc Purification process for the preparation of non-carrier added copper-64
US11978569B2 (en) 2023-08-28 2024-05-07 Curium Us Llc Purification process for the preparation of non-carrier added copper-64

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