JP7298874B2 - Method for producing radioactive isotope, and thermal separation device for producing radioactive isotope - Google Patents

Description

The present invention relates to a method for producing a radioactive isotope and a thermal separation apparatus for producing a radioactive isotope, and in particular, a radioactive The present invention relates to a method for producing isotopes and a thermal separation apparatus for producing radioactive isotopes.

Cu-64 and Cu-67, which are radioisotopes of copper, are promising as radioisotopes (radioisotopes: RI) for next-generation nuclear medicine diagnosis and treatment, but there is no production method at the stage of clinical practical use. has not been established.

Deuterons obtained from a deuteron accelerator (deuteron energy 10-50 MeV) are exposed to a converter for neutron generation (carbon, beryllium, lithium, etc.), and a zinc sample is irradiated with the generated fast neutrons to separate both nuclides. Alternatively, they can be synthesized simultaneously.

For example, in Patent Document 1, a raw material target is irradiated with fast neutrons from an accelerator, and the irradiation of one neutron n causes a (n, p) reaction in which one proton p is emitted to produce a radioactive isotope. It describes how to do it.

The method using fast neutrons does not have the limitation that a large amount of the sample cannot be used due to heat generation of the sample, which is a problem when irradiating the sample with a beam of charged particles such as protons. There are advantages over other production methods, such as the ability to produce radioactive RI. However, in order to take advantage of this advantage and secure a production amount that can be practically used in clinical practice, it is necessary to separate and purify a large amount of sample (up to 100 g) at a time and process it to obtain high-quality copper.

So far, we have been developing technology to synthesize both Cu-64 and Cu-67 nuclides from up to about 30 g of irradiated zinc (Zn) oxide and isolate them using a column separation method (see Non-Patent Document 1). I have been successful. However, when 30 g or more of irradiated zinc is processed by the column separation method, separation time of 10 hours or more is required, and the loss of radioactivity due to decay of the target nuclide during that time cannot be ignored. could not be hired.

On the other hand, Patent Documents 2 and 3 describe a method of irradiating Zn-68 with high-energy γ-rays to produce Cu-67 by thermal separation.

JP 2010-223935 A U.S. Patent Application Publication No. 2013/0083882 U.S. Patent Application Publication No. 2016/0040267

M. Kawabata et al. “Production and separation of 64Cu and 67Cu using 14 MeV neutrons” J Radioanal Nucl Chem (2014.9.6)

However, in the past, it was not considered to separate radioisotopes of copper synthesized using fast neutrons obtained in accelerators by thermal separation.

The present invention has been made to solve the above-described conventional problems, and by applying a thermal separation method that utilizes the vapor pressure difference between a radioactive copper isotope produced by fast neutrons and a zinc sample, An object of the present invention is to roughly separate radioactive copper isotopes in a short time without oxidizing a large amount of zinc sample of 100 g or more .

The present invention irradiates a sample of 100 g or more containing metallic zinc with fast neutrons obtained using an accelerator, and after placing the metallic zinc containing radioactive copper produced after neutron irradiation in a stainless steel container, 10 By heating under a high vacuum of ^-5 hPa, using the difference in vapor pressure between zinc and copper, only zinc, which has a high vapor pressure, is vaporized and roughly separated and removed in a short period of time , and the residue after zinc separation is recovered and removed. While obtaining radioactive copper by refining, the crudely separated metallic zinc is recovered and reused as a metallic zinc irradiation sample for radioisotope synthesis to solve the above problems.

Here, the radioactive copper is produced by ^{the 68} Zn(n, d+np) ⁶⁷ Cu reaction or ^{the 67} Zn(n, p) ⁶⁷ Cu reaction when the enriched Zn-68 sample or the enriched Zn-67 sample is irradiated with neutrons. can include Cu-67. Note that the enriched Zn-68 sample or the enriched Zn-67 sample may be a natural Zn sample.

The radioactive copper can also include Cu-64 produced by the ⁶⁴ Zn(n,p) ⁶⁴ Cu reaction upon neutron irradiation of the enriched Zn-64 sample. Note that the enriched Zn-64 sample may be a natural Zn sample.
Further, the radioactive copper is Cu-67 and Cu- 67 generated by ⁶⁸ Zn(n, d+np) ⁶⁷ Cu reaction or ⁶⁷ Zn(n, p) ⁶⁷ Cu reaction when Zn-68 or Zn-67 is irradiated with neutrons. , and Cu-64 produced by the ⁶⁴ Zn(n,p) ⁶⁴ Cu reaction when Zn-64 is irradiated with neutrons .

The present invention also comprises a tube containing a neutron-irradiated zinc-containing sample, a furnace for heating the tube, a stainless steel vacuum container containing the tube, and a vacuum container having a pressure of 10 ^-5 hPA. a vacuum pump for reducing the pressure to a high vacuum ; a vacuum gauge for detecting the pressure in the vacuum vessel; a leak valve for gradually returning the inside of the vacuum vessel from a high vacuum state to normal pressure; A cold trap for cooling and trapping and removing vaporized zinc disposed between and an on-line measurement of gamma rays emitted from an irradiated zinc sample containing radioactive copper from the outer surface of the tube. The object is likewise solved by providing a thermal separation apparatus for the production of radioisotopes, characterized in that it comprises a CZT detector installed to carry out .

Crude separation of zinc from a large zinc sample of 30 g or more containing radioactive copper generated by neutron irradiation, which is indispensable for obtaining high-strength radioactive copper essential for medical treatment using radioactive copper isotopes. If it is treated only by chemical ( column ) separation without it , the time required for the separation of zinc and copper will be long , and there will be problems such as losses due to attenuation of radioactive copper isotopes and an increase in the burden on workers. According to the present invention, zinc can be crudely separated in a short period of time by dry heat separation, making it possible to make the apparatus for chemical refining compact ( easier ) , opening up a way to use a large amount of zinc sample of 100 g or more .

Cu-64 is usually synthesized using a nickel sample, and Cu-67 is often synthesized using a zinc sample. do not have. According to the present invention, it is possible to simultaneously produce two nuclides, Cu-64 and Cu-67, in the same apparatus using a zinc-64 sample in a reaction using accelerator neutrons, or from a zinc-67 or zinc-68 sample. is.

Furthermore, the separated zinc can be recovered, concentrated by processing such as dissolution and solidification in an inert gas atmosphere, and reused as an irradiated sample for RI synthesis. Since concentrated zinc-68, zinc-67 and zinc-64 are expensive, the reusability of irradiated zinc samples is an important factor in reducing the manufacturing cost of medical RI.

In particular, when impurities are removed from the zinc sample before irradiation, only pure zinc can be irradiated, the amount of residual metal in the product after separation is reduced, and a high labeling rate and high quality radioisotope can be obtained. can be done.

As a result of experiments using the manufactured apparatus and actually irradiated metallic zinc , it was found that radioactive copper could be separated in a short period of time with a yield of 80 % or more. After separation, there is a small amount of zinc and radioactive copper that remain without sublimation. 67 final products could be obtained. Non-radioactive copper that lowers the specific radioactivity and impurity metals that lower the quality can be removed from the zinc in the sample in advance by thermal separation and purification using this device before irradiation.

A diagram showing a comparison of vapor pressure curves of zinc and copper, which is the principle of the present invention. FIG. 2 is a flow chart showing the processing procedure in the embodiment of the present invention; FIG. Cross-sectional view schematically showing the state in which a zinc sample is similarly irradiated with neutrons. A pipeline diagram showing the overall configuration of a heat separator used in the present invention. A flow diagram showing the procedure for heat separation as well Diagram showing comparison of changes over time in γ-ray peak area counts derived from (A) Cu-67 and (B) Zn-69m in samples. Flow chart showing an example of a copper refining procedure after thermal separation in the embodiment Cross-sectional view showing a configuration example of a zinc recovery device. Similarly, a flowchart showing an example of the procedure for fabricating a sample for irradiation

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In addition, the present invention is not limited by the contents described in the following embodiments and examples. In addition, the configuration requirements in the embodiments and examples described below include those that can be easily assumed by those skilled in the art, those that are substantially the same, and those that fall within the so-called equivalent range. Furthermore, the constituent elements disclosed in the embodiments and examples described below may be combined as appropriate, or may be selected and used as appropriate.

Figure 1 compares the vapor pressure curves of zinc and copper. By utilizing the vapor pressure difference between zinc (Zn) and copper (Cu) in the target temperature range around 600° C. under reduced pressure, it is possible to sublime only zinc and leave copper as a solid. At this time, oxidation of zinc can be prevented by sublimation under reduced pressure. In the present invention, utilizing such a principle, zinc is thermally separated by a wet method without using a large amount of chemicals.

FIG. 2 shows the processing procedure of the embodiment of the present invention.

First, in step 100, as illustrated in FIG. 3, a Zn sample 18 is irradiated with neutrons (n) 16 to synthesize RI from metallic zinc.

That is, deuterons (d) 12 having an energy of, for example, 40 MeV or more obtained in the accelerator main body 10 are absorbed by a carbon or beryllium target 14 placed in a vacuum, and undergo a C(d,n) reaction or Be( d, n) releases fast neutrons (n) 16 into the atmosphere. Cu-67 and Cu-64 can be synthesized by a nuclear reaction between the neutron 16 and a zinc sample 18 such as enriched Zn-68, enriched Zn-64, and natural Zn.

Specifically, by irradiating stable enriched isotope Zn-68 with neutron n, the target atomic nucleus absorbs neutron n and releases deuterium nucleus d, neutron n, and proton p by the following formula (1 ) to synthesize Cu-67.
⁶⁸ Zn(n, d+np) ⁶⁷ Cu (1)

Also, by irradiating stable enriched isotope Zn-67 with neutron n, Cu-67 is synthesized by the nuclear reaction of the following formula (2) in which the target atomic nucleus absorbs neutron n and emits proton p. be.
⁶⁷ Zn(n, p) ⁶⁷ Cu (2)

Also, by irradiating stable enriched isotope Zn-64 with neutron n, the target atomic nucleus absorbs neutron n and emits proton p. be.
⁶⁴ Zn(n, p) ⁶⁴ Cu (3)

These nuclear reactions are identical in that they chemically separate Cu from Zn, since the irradiated target is Zn, and different masses of zinc 68 or zinc 67 and zinc 64 samples are used for Cu-67 or Cu-67 respectively. 64 can be isolated by applying common isolation methods.

Next, proceed to step 110 to rapidly and highly efficiently separate radioactive copper produced by irradiating a large amount of expensive zinc sample with neutrons obtained in an accelerator, and to reuse the expensive zinc sample after separation. Zinc is removed by thermal separation using a thermal separator with high efficiency and recoverable performance.

FIG. 4 shows a configuration example of the heat separator. This thermal separator 22 heats the irradiated metallic zinc containing Cu-67 or Cu-64 in a test tube, for example a quartz recovery tube 24, and vaporizes and separates only zinc with a high vapor pressure. In order to prevent the oxidation of zinc, the inside of the system is kept in a vacuum state so that the separation can be performed at a lowered vaporization temperature.

The thermal separator 22 includes a quartz recovery tube 24 containing a neutron-irradiated Zn sample 18 containing metallic zinc, a quartz inner cylindrical tube 26, a stainless steel (SUS) inner cylindrical tube 28, the quartz recovery tube 24, and the like. A vertically movable electric furnace 30 for heating from the surroundings, a SUS vacuum vessel 32 containing the quartz recovery tube 24 and the like, and a turbo molecular pump for reducing the pressure in the vacuum vessel 32. a vacuum pump 34, a cold trap 36 disposed between the vacuum vessel 32 and the vacuum pump 34 for trapping and removing vaporized zinc, and irradiation from the outer surface of the quartz recovery tube 24. and a CZT detector 38 installed for on-line measurement of radiation (gamma rays) emitted from the zinc sample 18 . In the figure, 40 is a collimator for the CZT detector 38 to limit the radiation emitted from the zinc sample 18, 42, 44 are vacuum gauges, 46 is a leak valve, and 48 is a butterfly valve. .

The CZT detector 38, which is a CdZnTe compound semiconductor detector, can measure the energy and intensity of gamma rays emitted from RI on-line. On-line measurements are important for immediate determination of whether the separation process is progressing smoothly without any surprises. Various types of RI such as Cu-64 and Cu-67 are mixed in the RI generated in the zinc sample 18, and each RI emits γ-rays of energy unique to that RI. Therefore, if the CZT detectors 38 are set everywhere in the vertical direction around the electric furnace 30, when the temperature of the electric furnace 30 is increased, the energy of γ rays detected by the CZT detectors 38 at a certain location is measured. If possible, the information that the RI that emits the gamma ray has come to the place can be obtained by "in situ observation". That is, since it is possible to track changes from moment to moment, it is possible to visually observe various behaviors of RI caused by thermal separation. This is valuable data for successful thermal separation because it can instantly determine unexpected situations.

The cold trap 36 is intended to concentrate the vaporized zinc into a solid during decompression operation, but zinc does not actually move to the cold trap 36 .

When returning from a high vacuum state to normal pressure, the leak valve 46 gradually restores the normal pressure so as not to interfere with the sample, the quartz device, the vacuum gauges 42 and 44, etc. in the vacuum.

FIG. 5 shows a procedure for thermally separating the target nuclide Cu-64 and/or Cu-67 by irradiating the Zn sample 18 with the neutrons 16 using the thermal separation device 22 .

Beginning at step 200 , irradiated zinc metal ( 18 ) is introduced into quartz collection tube 24 .

Next, in step 210, the quartz recovery tube 24 is placed in the electric furnace 30 together with the quartz inner cylindrical tube 26, the stainless steel inner cylindrical tube 28, and the vacuum vessel 32. Move 30 up and down.

Proceeding next to step 220 , liquid nitrogen LN ₂ is introduced into the cold trap 36 .

Next, proceeding to step 230 , the CZT detector 38 is installed facing the Zn sample 18 from the outer surface of the electric furnace 30 .

Next, in step 240, the pressure is reduced by the vacuum pump 34, and the vacuum gauge 44 confirms that the pressure is about 10 ^-5 hPA.

Next, in step 250, the electric furnace 30 heats up to 600° C. and holds for about 70 minutes.

Proceeding to step 260, the CZT detector 38 is then used to examine the change over time in the counts of peak areas originating from RI in the sample, such as Cu-64, Cu-67, Zn-69m, and Zn-65.

FIG. 6 compares the change over time in the count of the γ-ray peak area originating from Cu-67 and the change over time in the count of the γ-ray peak area originating from Zn-69m. For Cu-67 (185 keV) shown in FIG. 6A, γ-ray absorption by zinc decreases as thermal separation progresses, so it slightly increases around the right shoulder but does not decrease. That is, Cu-67 remains at the sample position. On the other hand, Zn-69m shown in FIG. 6(B) significantly decreased as the thermal separation progressed, and sublimated from the sample position together with non-radioactive zinc to be separated.

While observing the spectrum of the CZT detector 38, the process proceeds to step 270, for example, heating is stopped at a predetermined holding time and the electric furnace 30 is lowered.

Next, in step 280, after confirming that the temperature display has become, for example, 200° C. or less, the valves around the cold trap 36 are closed, the leak valve 46 is opened to return to normal pressure, and in step 290, the vacuum container 32 is opened. .

Then, the yield of zinc is evaluated by weight measurement of the quartz collection tube 24 and the deposited portion of the sublimated zinc 20 .

After zinc is removed by the procedure of FIG. 5 using the thermal separator 22 shown in FIG. 4, the process returns to step 120 of FIG. 2 to recover the residues (Cu-64, Cu-67). That is, after thermal separation, the residue (about 10 mg) in the quartz recovery tube 24 containing the sample is a mixture of the target nuclide (Cu-64, Cu-67), impurity metals other than zinc, and zinc oxide ZnO. .

Therefore, the process proceeds to step 130 in FIG. 2, and refinement is performed according to the copper refining procedure after thermal separation shown in FIG.

That is, first, in step 300, for example, it is dissolved in 8M hydrochloric acid (10 mL or less).

Next, in step 310, the pH is adjusted to suit the Cu adsorption resin.

In step 320, a resin for Cu adsorption such as CuResin or Chelex 100 (commercially available) can be used.

If it cannot be removed in step 320, it is possible to proceed to step 330 and remove it using an anion exchange column such as AG1x8 (commercially available).

The adsorbed Cu can be dissolved alone with concentrated hydrochloric acid.

In this way, zinc and other metals not completely removed with a small amount of metal separation resin are removed, and in step 140, final products of Cu-64 and Cu-67 are obtained.

On the other hand, the concentrated zinc sample is very expensive at about 100,000 yen per gram, whereas the zinc sample consumed in the chemical reaction with neutrons is less than 1/1,000,000 of its weight before irradiation, and most of it is zinc. The sample does not lose weight. Therefore, it is important from the viewpoint of economical production of radioactive copper to efficiently recover zinc samples for reuse after thermal separation.

Therefore, zinc is sublimated (thermally separated) in the procedure of FIG. 5 using the thermal separation device 22 shown in FIG. 4 to remove Cu, and then zinc is recovered using the zinc recovery device 50 illustrated in FIG. .

The zinc recovery apparatus 50 shown in FIG. 8 includes a recovery container 52 having a quartz recovery tube 24 disposed at the bottom, a protective container 54 provided outside thereof, an adapter 56, and a protective container 58 provided outside thereof. , a vacuum vessel 60, an electric furnace 62, a vacuum pump 64 for evacuating the inside of the vacuum vessel 60, a trap 66 provided midway between the vacuum vessel 60 and the vacuum pump 64, and cooling the trap 66 A liquid nitrogen (LN ₂ ) container 68 is mainly used for this purpose. In the figure, 76 is a vacuum gauge.

Hereinafter, the procedure for fabricating the sample for irradiation (the same applies to the reuse of Zn after RI separation) will be described with reference to FIG.

First, in step 400, the sublimated zinc 20 deposited in the middle of the quartz recovery tube 24 is taken out together with the quartz recovery tube 24. 56.

Next, in step 420 , the sublimated zinc 20 is double-sealed using the quartz vacuum container 60 and protective container 58 .

Next, in step 430, the vacuum pump 64 is used to evacuate the air inside the vacuum container 60 in order to prevent oxidation of zinc, and in step 440, an inert gas (for example, a mixed gas of nitrogen N ₂ and hydrogen H ₂ ) is After replacement, the inside of the vacuum vessel 60 is filled to normal pressure.

Next, in step 450 , the electric furnace 62 is heated up to, for example, about 800° C. and held for several minutes to melt the sublimated zinc 20 adhering to the wall of the quartz recovery tube 24 and drop it into the recovery container 52 .

Next, in step 460, the sample is cooled, and the pelletized zinc 70 solidified in the quartz collection tube 24 is taken out and reused as the sample for the next irradiation.

In this way, expensive zinc samples can be reused and recovered with high efficiency.

Copper has been removed from the recovered zinc in advance, making it possible to use zinc metal with less impurity copper.

This process can also be applied to Zn that has not been irradiated with neutrons. By removing Cu in advance by thermal separation and purifying Zn before neutron irradiation, the specific radioactivity of the synthesized Cu-64 and Cu-67 is increased. be able to.

The thermal separator 22 can also be applied to thermal separation other than copper, and can separate P-32 and P-33 from sulfur, for example, by utilizing the difference in vapor pressure.

DESCRIPTION OF SYMBOLS 10... Accelerator body 12... Deuteron 14... Carbon/beryllium target 16... Neutron 18... Zinc sample 20... Zinc sublimation 22... Thermal separator 24... Quartz recovery tube 26... Quartz inner tube 28... Stainless steel inner tube 30, 62 Electric furnace 38 CZT detector 32, 60 Vacuum container 34, 64 Vacuum pump 36 Cold trap 46 Leak valve 42, 44, 76 Vacuum gauge 50 Zinc recovery device 52 Recovery container 54, 58 Protection Container 66 Trap 68 Liquid nitrogen container 70 Zinc pellet

Claims (5)

Irradiating a sample of 100 g or more containing metallic zinc with fast neutrons obtained using an accelerator,
After placing the metal zinc containing radioactive copper that has been irradiated with neutrons in a stainless steel container, it is heated under a high vacuum of 10 ^-5 hPA,
Using the difference in vapor pressure between zinc and copper, only zinc with high vapor pressure is vaporized and roughly separated and removed.
Manufacture of radioactive isotopes characterized by recovering and purifying the residue after zinc separation to obtain radioactive copper, while recovering crudely separated metallic zinc and using it again as a metallic zinc irradiation sample for radioisotope synthesis. Method. The radioactive copper contains Cu-67 generated by ⁶⁸ Zn(n, d+np) ⁶⁷ Cu reaction or ⁶⁷ Zn(n, p) ⁶⁷ Cu reaction when Zn-68 or Zn-67 is irradiated with neutrons. The method for producing a radioisotope according to claim 1, characterized in that: 2. Production of radioisotope according to claim 1, characterized in that said radioactive copper contains Cu-64 produced by ⁶⁴ Zn(n,p) ⁶⁴ Cu reaction when Zn-64 is irradiated with neutrons. Method. When the radioactive copper irradiates Zn-68 or Zn-67 with neutrons, ⁶⁸ Zn(n,d+np) ⁶⁷ Cu reaction or ⁶⁷ Zn(n,p) ⁶⁷ When Cu-67 generated by the Cu reaction and Zn-64 are irradiated with neutrons, ⁶⁴ Zn(n,p) ⁶⁴ 2. The method for producing a radioisotope according to claim 1, wherein Cu-64 produced by a Cu reaction is also included. a tube containing a sample containing neutron-irradiated zinc;
a furnace for heating the tube;
a stainless steel vacuum vessel that houses the tube;
a vacuum pump for reducing the pressure in the vacuum vessel to a high vacuum of 10 ^-5 hPA;
a vacuum gauge that detects the pressure in the vacuum vessel;
a leak valve for gradually returning the inside of the vacuum container from a high vacuum state to normal pressure;
a cold trap disposed between the vacuum vessel and the vacuum pump for cooling and trapping and removing vaporized zinc;
a CZT detector positioned for on-line measurement of gamma rays emitted from an irradiated zinc sample containing radioactive copper from the outer surface of said tube;
A thermal separation device for producing radioactive isotopes, comprising:

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