JP2018084570A - Ri-labelled compound manufacturing installation and ri-labelled compound manufacturing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an RI-labelled compound manufacturing installation capable of recycling a target gas, having a high production efficiency of radioactive isotopes, capable of making radiation exposure approach zero as far as possible, and further capable of supplying at a low price, and an RI-labelled compound manufacturing method.SOLUTION: A gas charge part 10 charges a target gas in a nuclear reaction vessel 10a, and a gas sealing part 11 hermetically seals the nuclear reaction vessel 10a in which the target gas was charged. A radiation irradiation part 12 irradiates radiation to the nuclear reactor 10a in which the target gas was hermetically sealed for a predetermined time to cause a nuclear reaction of the target gas, an RI-labelled compound synthesis part 13 makes radioactive isotopes contained in the target gas after nuclear reaction react with a liquid compound 13a after opening of the nuclear reactor 10a to synthesize an RI-labelled compound. Then, an impurity trapping part 14 removes impurities from the target gas after the reaction and the target gas after the removal is returned to the nuclear reactor 10a.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an RI-labeled compound manufacturing apparatus and an RI-labeled compound manufacturing method.

  In recent years, positron emission tomography (hereinafter referred to as PET) examination and single photon emission tomography (hereinafter referred to as SPECT) examination are cancer diagnostic methods using radiation. The trend is.

  According to a report from the National Cancer Center on July 15, 2016, 370,000 people died of cancer in 2015 in Japan, and 10.1 million people will be newly discovered as cancer patients in 2016. Expected. The cancer mortality rate in Japan, where health care has been enhanced, is higher than in the United States, Europe, etc., so the above-described PET inspection and SPECT inspection are frequently performed.

  In PET inspection and SPECT inspection, radioisotope labeled compounds (RI labeled compounds) are basically used. This RI-labeled compound is a compound that can be distinguished from a normal compound by replacing an atom at a specific position of a compound that is likely to be accumulated in a lesion site of cancer with a radioisotope (RI). In the PET examination, as a representative example of the RI-labeled compound, 18F-2-fluoro-2-deoxy-D-glucose (referred to as 18F-FDG) in which 18-fluorine isotope (18F) is incorporated into glucose (glucose) is used. When administered to a cancer patient, the positrons emitted from 18F of 18F-FDG are annihilated with electrons, and two gamma rays with energy of 511 keV are detected, and the distribution of 18F-FDG in the body is photographed. Identify cancerous sites with significant metabolism. On the other hand, in the SPECT examination, a labeled compound incorporating 99m technetium isotope (99mTc) that emits gamma rays as an RI-labeled compound is administered to a cancer patient, and 140 keV gamma rays released from 99mTc are detected. Photograph 99mTc distribution. Since a labeled compound having 99mTc is accumulated in the blood, the SPECT examination is used for, for example, myocardial blood flow imaging and brain function imaging.

  In both PET inspection and SPECT inspection, since a special RI-labeled compound is used, the inspection cost is high. For example, in SPECT examination, more than 1 million patients visited Japan in 2007, the cost is 150 billion yen, 99mTc accounts for almost 100% of SPECT, while PET examination is from 3 times this It takes 4 times. In Japan, spending several hundred billion yen on PET and SPECT examinations every year for diagnostic imaging for cancer treatment.

  By the way, 18F of 18F-FDG used in PET inspection is usually manufactured as follows. First, the 18-oxygen isotope (18O) is irradiated with a proton beam by a small cyclotron, and 18F is produced from 18O by utilizing the 18O (p, n) 18F reaction.

  Here, the abundance ratio of 16-oxygen isotope (16O) is 99.762%, the abundance ratio of 17-oxygen isotope (17O) is 0.039%, and 18-oxygen isotope (18O) ) Is very low at 0.201%. Therefore, expensive 18O concentrated water is used in the production of 18F for PET inspection. For example, Japanese Unexamined Patent Application Publication No. 2004-59356 (Patent Document 1) discloses a technique related to 18O concentrated water for 18F fluoride ion production raw material. Since 18O concentrated water is expensive, there is no use of 18O concentrated water in developing countries.

  Further, when a small cyclotron used for manufacturing 18F is used, it is inevitable that an operator involved in manufacturing 18F is exposed to considerable radiation exposure. That is, 18F is produced by irradiating 18O concentrated water with a high-intensity proton beam from a small cyclotron, so that a large amount of radioactive material is inevitably generated in the extraction window of this proton beam. Since the beam extraction window may be damaged, it is necessary to replace the beam extraction window periodically and to maintain the proton beam irradiation apparatus periodically. This operation inevitably generates a large amount of radiation exposure.

  Therefore, in recent years, various methods for producing 18F that do not use 18O concentrated water have been developed. For example, Japanese Patent Laying-Open No. 2006-3363 (Patent Document 2) discloses a technique for producing a high yield of 18F fluorine gas using 18O oxygen gas. As a technique for producing a radioactive gas isotope using a target gas, Japanese Patent Application Laid-Open No. 2010-164477 (Patent Document 3) circulates and cools a gas filled in a reaction chamber during a nuclear reaction, and pressure in the reaction chamber An apparatus for producing a radioactive gas isotope is disclosed that reduces the thickness of the irradiation window through which a charged particle beam is transmitted.

JP 2004-59356 A JP 2006-3363 A JP 2010-164477 A

  However, the technique described in the above-mentioned patent document requires an expensive and highly concentrated 18O isotope for producing 18F, and there is a problem that the yield of 18F is poor. Moreover, since the manufacture of 18F uses a high-intensity proton beam from a small cyclotron, there is a problem that it is difficult to take measures to reduce the possibility of radiation exposure.

  The present invention has been made to solve the above problems. RI-labeled compound manufacturing apparatus and RI-labeled compound manufacturing method capable of reusing target gas, having high production efficiency of radioisotopes, approaching the possibility of radiation exposure to zero, and supplying at low cost The purpose is to provide.

  As a result of intensive studies, the present inventor has completed the novel RI-labeled compound manufacturing apparatus and RI-labeled compound manufacturing method according to the present invention. That is, the present invention is an RI-labeled compound manufacturing apparatus for manufacturing an RI-labeled compound, and includes a gas filling unit, a gas sealing unit, a radiation irradiation unit, an RI-labeled compound synthesis unit, and an impurity trap unit. The gas filling unit fills the nuclear reaction container with the target gas, and the gas sealing unit seals the nuclear reaction container filled with the target gas. The radiation irradiating unit irradiates a nuclear reaction container sealed with the target gas for a predetermined time to cause the target gas to undergo a nuclear reaction. The RI-labeled compound synthesis unit synthesizes the RI-labeled compound by reacting the radioisotope contained in the target gas after the nuclear reaction with a liquid compound after opening the nuclear reaction vessel. The impurity trap unit removes impurities from the target gas after the reaction, and returns the target gas after the removal to the nuclear reaction vessel.

  The present invention is also an RI labeled compound manufacturing method for manufacturing an RI labeled compound, comprising a gas filling step, a gas sealing step, a radiation irradiation step, an RI labeled compound synthesis step, and an impurity trap step. The gas filling step fills the nuclear reaction container with the target gas, and the gas sealing step seals the nuclear reaction container filled with the target gas. In the radiation irradiation step, a nuclear reaction container sealed with the target gas is irradiated with radiation for a predetermined time to cause the target gas to undergo a nuclear reaction. The RI-labeled compound synthesis step synthesizes the RI-labeled compound by reacting a radioisotope contained in the target gas after the nuclear reaction with a liquid compound after opening the nuclear reaction vessel. In the impurity trap step, impurities are removed from the target gas after the reaction, and the target gas after the removal is returned to the nuclear reaction vessel.

  In the present invention, the target gas can be reused, the production efficiency of the radioisotope is high, the possibility of radiation exposure is brought close to zero, and it can be supplied at a low price.

It is a conceptual diagram of the RI labeling compound manufacturing apparatus which concerns on embodiment of this invention. It is a front photograph of the prototype of the RI labeling compound manufacturing apparatus concerning the embodiment of the present invention. It is the front photograph and perspective view of the prototype of the RI labeling compound manufacturing apparatus which concern on embodiment of this invention. It is a perspective photograph which shows a mode that the prototype of RI labeling compound manufacturing apparatus is installed in an electron beam type accelerator, and 18F is manufactured. It is a perspective photograph which shows a mode that 18F manufactured with the prototype of the RI labeling compound manufacturing apparatus is analyzed. It is a spectrum of a radiation at the time of completion of manufacture of 18F. It is an attenuation curve of the radiation dose for every elapsed time.

  Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings to provide an understanding of the present invention. In addition, the following embodiment is an example which actualized this invention, Comprising: The thing of the character which limits the technical scope of this invention is not.

  FIG. 1 is a conceptual diagram of an RI-labeled compound production apparatus according to an embodiment of the present invention. As shown in FIG. 1, the present invention is an RI labeled compound manufacturing apparatus 1 for manufacturing an RI labeled compound, which is a gas filling unit 10, a gas sealing unit 11, a radiation irradiation unit 12, and an RI labeled compound synthesis unit. 13 and an impurity trap part 14.

  The gas filling unit 10 fills the nuclear reaction container 10a with the target gas, and the gas sealing unit 11 seals the nuclear reaction container 10a filled with the target gas. The radiation irradiation unit 12 irradiates the nuclear reaction vessel 10a sealed with the target gas for a predetermined time to cause the target gas to undergo a nuclear reaction, and the RI labeling compound synthesis unit 13 opens the nuclear reaction vessel 10a, By reacting the radioisotope contained in the target gas after the nuclear reaction with the liquid compound 13a, an RI-labeled compound is synthesized. And the impurity trap part 14 removes an impurity from the target gas after the reaction, and returns the target gas after the removal to the nuclear reaction vessel 10a.

  In the present invention, the target gas is subjected to nuclear reaction by irradiation with radiation to generate a radioisotope, and then the target gas containing the radioisotope is reacted with the liquid compound 13a as it is. Therefore, it is possible to integrate the production of radioisotopes and the synthesis of RI-labeled compounds into one device, and the RI-labeled compounds can be obtained immediately after the production of radioisotopes. Efficiency can be increased.

  By removing impurities from the target gas after the reaction of the RI-labeled compound and reusing the target gas after the removal, the production efficiency of the RI-labeled compound can be increased, and it can be supplied at a low price. In particular, in the present invention, the target for obtaining the radioisotope is not a liquid but a gas, so that the target gas can be easily transported and handled, and the target gas after the nuclear reaction can be easily returned to the nuclear reaction vessel 10a. The target gas can be circulated. If the target is a liquid and the target liquid is irradiated with radiation, the target liquid undergoes radiolysis along with the nucleation of the radioisotope, resulting in bubbles in the target liquid, and the target after the nuclear reaction by the bubbles. It may be difficult to transport the liquid.

  Furthermore, in the present invention, the target gas is made into a circulation system, the radioisotope is obtained and the RI-labeled compound is continuously synthesized, and these controls can be performed by a control device such as a computer. That is, since each component of the present invention can be performed fully automatically, an RI-labeled compound can be obtained by remote control. Therefore, there is almost no frequency that an operator approaches the apparatus, and the possibility of radiation exposure can be reduced.

  Here, there are no particular limitations on the types of target gas and radiation, but they are appropriately designed according to the target RI-labeled compound. For example, when the RI labeling compound is 18F-FDG, neon gas is selected as the target gas and gamma rays are selected as the radiation. Neon (Ne) is a rare gas element that does not cause a chemical reaction with other atoms and molecules, and is inexpensive. On the other hand, 18F is produced indirectly through β decay from 20Ne (γ, 2n) 18Ne to 18F by irradiating neon with gamma rays, or directly produced from 20Ne (γ, pn) 18F reaction. I can do it. Further, the nuclear reaction described above is a photonuclear reaction, and the generation of radioactive materials that become radioactive waste is remarkably reduced. Therefore, the neon gas after irradiation can suppress the generation of unnecessary radioactive substances and can be completely recovered and reused. Further, 18F can be produced at low cost without using expensive 18O concentrated water.

  Further, the configuration of the gas filling unit 10 is not particularly limited. For example, a circulation type compressor capable of circulating the target gas can be employed. In this case, a first pipe 10d is provided for communicating the outlet 10b through which the target gas is sent from the compressor and the inlet 10c of the nuclear reaction vessel 10a. Further, the impurity trap unit 14 removes impurities from the target gas after the reaction exhausted from the exhaust port 13b of the RI labeling compound synthesis unit 13, and uses the second pipe 14a to convert the target gas after the removal into the gas. By introducing it into the first supply port 10e of the compressor of the filling unit 10, circulation of the target gas is facilitated.

  Although there is no limitation in particular in the structure of the nuclear reaction container 10a, For example, the raw material which is excellent in heat conduction can be employ | adopted. Specifically, by adopting a SiC ceramic container having a thermal conductivity similar to that of copper, even if heat is generated in the container due to absorption of radiation such as gamma rays, heat is dissipated by the heat conduction, An increase in pressure can be prevented. Of course, the RI-labeled compound can be produced in such a range that the target gas does not correspond to the compressed gas of the high-pressure gas regulation law (the gas whose pressure becomes 10 MPa or more at room temperature). Further, since SiC does not chemically react with 18F, the purity of the produced 18F can be guaranteed. In addition, a container whose inner surface is coated with a Teflon (registered trademark) material excellent in corrosion resistance may be adopted as a test in consideration of the erodibility of generated fluorine. A circulation cooling unit 15 that cools the outer surface of the nuclear reaction vessel 10a by circulating a cooling medium such as liquid nitrogen may be provided.

  Although there is no limitation in particular in the structure of the gas sealing part 11, For example, the 1st pressure valve 11a connected to the inlet 10c of the nuclear reaction container 10a, and the 2nd connected to the exhaust port 10f of the nuclear reaction container 10a are included. A pressure valve 11b and a first pressure gauge 11c provided between the exhaust port 10f and the second pressure valve 11b are provided. When the gas filling unit 10 fills the nuclear reactor vessel 10a with the target gas, the gas sealing unit 11 opens the first pressure valve 11a, closes the second pressure valve 11b, and the first pressure gauge. While monitoring the pressure value of 11c, the target gas is filled until the pressure of the target gas in the nuclear reaction vessel 10a reaches a predetermined pressure value. Next, when the pressure value of the first pressure gauge 11c reaches a predetermined value, the gas sealing unit 11 closes the first pressure valve 11a and seals the nuclear reaction vessel 10a. Moreover, the gas sealing part 11 detects abnormality by monitoring the 1st pressure gauge 11c. The gas sealing unit 11 continues to close the first pressure bubble 11a and the second pressure valve 11b during the radiation irradiation, and during that time, the nuclear reaction of the target gas in the nuclear reaction vessel 10a proceeds and is radioactive. Isotopes are generated. Thereafter, when radiation irradiation stops, the gas sealing unit 11 releases the target gas after the nuclear reaction from the nuclear reaction vessel 10a by opening the second pressure valve 11b.

  Here, the pressure of the target gas filled in the nuclear reaction vessel 10a is not particularly limited, but for example, a pressure higher than normal pressure is preferable. In the present invention, since the target gas is used, the production yield of the radioisotope is deteriorated as compared with the case where the target liquid is irradiated with radiation. Therefore, the production yield of the radioisotope can be improved by increasing the pressure of the target gas in the nuclear reaction vessel 10a and lowering the temperature. The pressure of the target gas in the nuclear reaction vessel 10a is preferably within a range that does not correspond to the compressed gas of the high-pressure gas regulation law, and is set within a range of 3 MPa to 10 MPa, for example. Further, by increasing the pressure of the target gas in the nuclear reaction vessel 10a, the target gas after the nuclear reaction can be easily discharged when the second pressure valve 11b is opened.

  In addition to the first pressure valve 11a, a second pressure is applied in order from the outlet 10b to the first pipe 10d between the outlet 10b of the gas filling unit 10 and the inlet 10c of the nuclear reaction vessel 10a. A total of 10 g, a third pressure valve 10 h, a pressure adjustment valve 10 i, and a third pressure gauge 10 j are provided. The second pressure gauge 10g measures the pressure of the target gas between the delivery port 10b and the third pressure valve 10h. The third pressure valve 10 h controls the delivery of the target gas from the delivery port 10 b of the gas filling unit 10. The pressure adjustment valve 10i adjusts the pressure of the target gas when the pressure of the target gas sent from the third pressure valve 10g is excessive. The third pressure gauge 10j measures the pressure of the target gas between the pressure adjustment valve 10i and the first pressure valve 11a.

  The configuration of the radiation irradiation unit 12 is not particularly limited. For example, when the radiation is gamma rays, the electron beam irradiation unit 12a that irradiates an electron beam having a predetermined energy and the nuclear reaction vessel 10a are provided in the vicinity of the electron beam irradiation unit 12a. And a gamma ray emitting unit 12b that emits gamma rays when irradiated with rays. Thereby, gamma rays can be easily irradiated. Here, a target that generates gamma rays by an electron beam such as tungsten (W), platinum (Pt), tantalum (Ta), or the like is selected as the gamma ray emitting unit 12b. Specifically, by irradiating tungsten with an electron beam having energy of 30 MeV, bremsstrahlung gamma rays are generated and used as radiation.

  Here, when irradiating 18O concentrated water with a proton beam, a nuclear reaction occurs based on a strong nuclear force. Therefore, the extraction window is strongly activated by this nuclear reaction. On the other hand, when using gamma rays of the target bremsstrahlung by irradiating the target with an electron beam, the target window is made of Si or C, and the half-life of the residual radioactive material generated by the photonuclear reaction is Since it is on the order of milliseconds, there is virtually no radioactive material. Further, no long-lived residual radioactive material is generated, and there is no need to replace the target device. Therefore, in the present invention, the possibility of radiation exposure can be reduced even in such a point.

  For example, when an electron beam accelerator (electronic linac) is used for the electron beam irradiation unit 12a, it can be operated with a single switch, and control of full automation and remote operation becomes easy. The proton beam of the cyclotron requires a skilled person who has sufficient knowledge for handling, but the electron beam accelerator has an advantage that even an amateur can handle it. In addition, the cyclotron needs to be renewed, and if the cyclotron is treated as a radioactive material, enormous costs are required, which is a major problem. However, with an electron beam accelerator, there is almost no radioactive material, and most of it is industrially discarded. Since it can be processed as a product, the electron beam accelerator is advantageous in terms of disposal.

  Furthermore, the nuclear reaction vessel 10a (target target) can be made thicker by using gamma rays without using the proton beam of the cyclotron. For example, when 18F is generated by irradiating a proton beam from a cyclotron to 18O concentrated water, that is, when an 18O (p, n) 18F reaction is used, the energy of the proton beam is 15 MeV, and the current is 50 mA to 70 mA. It is. The proton beam needs to be taken out from the cyclotron through the extraction window (Harbar foil, mainly Ni) into the atmosphere, and the proton beam needs to pass through the target window of the container containing the target. is there. Here, the thickness at which the 15 MeV proton beam stops is about 6 mm with 18O concentrated water. If it is desired to produce a radioisotope, the proton beam current to the target will increase. Then, the extraction window and the target window irradiated with the proton beam are strongly activated, and each window is damaged. For example, it is necessary to replace the extraction window and the target window after use for about two weeks. This replacement work is laborious, and the operator may be exposed to radiation during the replacement. In the present invention, the possibility of radiation exposure can be drastically reduced by using gamma rays as radiation and generating the gamma rays by an electron beam accelerator. Also, gamma rays have high penetrating power and are transmitted even at a target thickness of 20 cm at an extremely low temperature of 4K. Practically, the production amount of 18F corresponding to the amount of RI-labeled compound for PET of 18F-FGD for about 2 persons can be obtained by irradiation with neon gas at room temperature for 1 hour.

  Further, the predetermined time (irradiation time) for emitting radiation is not particularly limited. For example, it is preferably set to half the half-life of the generated radioisotope. When the radioisotope is 18F, since the half-life of 18F is 110 minutes, for example, the irradiation time is set to 55 minutes.

  Now, when the radiation irradiation unit 12 stops the radiation irradiation and the gas sealing unit 11 opens the second pressure valve 11b, the target gas after the nuclear reaction is released from the nuclear reaction vessel 10a, and the RI labeling compound synthesis unit 13 is released. It is sent to.

  Here, the 3rd piping 11d which connects the 2nd pressure valve 11b and the 2nd supply port 13c of RI labeling compound synthesizing part 13 is provided, and the 2nd pressure valve is provided in this 3rd piping 11d. In order from 11b, a pressure reducing valve 11e and a fourth pressure gauge 11f are provided. The pressure reducing valve 11e reduces the pressure of the target gas when the pressure of the target gas is excessive due to the opening of the second pressure valve 11b. The fourth pressure gauge 11 f measures the pressure of the target gas between the pressure reducing valve 11 e and the second supply port 13 c of the RI labeling compound synthesizing unit 13.

  The configuration of the RI-labeled compound synthesizing unit 13 is not particularly limited. For example, when the radioisotope is 18F and the RI-labeled compound is 18F-FDG, the RI-labeled compound synthesizing unit 13 is liquid as the compound 13a. 13d for storing the glucose, and a bubbling unit 13e communicating with the second supply port 13c for bubbling the target gas after the nuclear reaction to the stored compound 13a. Thus, by bubbling the target gas after the nuclear reaction in the compound 13a (liquid glucose), the radioisotope 18F in the target gas reacts with the compound 13a, and the RI-labeled compound can be easily synthesized. I can do it. Specifically, the OH group of glucose is substituted with 18F to produce 18F-FDG. Further, when the target gas is neon gas, neon gas that has not undergone nuclear reaction is inactive, and thus passes without reacting even when bubbled by the compound 13a. Thereby, neon gas can be collect | recovered and it can utilize again as a raw material.

  The RI-labeled compound synthesizing unit 13 includes a third supply port 13f for supplying the compound 13a to the upper side in the storage unit 13d, and a take-out port 13g for taking out the RI-labeled compound after the reaction in the lower side of the storage unit 13d. The provision facilitates replenishment of compound 13a and removal of the RI-labeled compound. The third supply port 13f is provided with a supply valve 13h for controlling the supply of the compound 13a, and the take-out port 13g is provided with a take-out valve 13i for controlling the removal of the RI-labeled compound after the reaction. The RI labeling compound synthesizing unit 13 may further include a temperature adjusting unit that keeps the temperature of the storage unit 13d constant as necessary.

  By the way, the target gas from which the radioisotope has been lost by the compound 13a is exhausted from the exhaust port 13b of the RI-labeled compound synthesizing unit 13, passes through the second pipe 14a of the impurity trap unit 14, and is first in the gas filling unit 10. To the supply port 10e.

  Here, the RI-labeled compound is not necessarily limited to 18F-FDG. For example, when the radioisotope is 18F and the RI-labeled compound is Na-18F, the storage unit 13d of the RI-labeled compound synthesis unit 13 stores an aqueous sodium hydroxide (NaOH) solution as the compound 13a, and the bubbling unit 13e. Bubble the target gas after the nuclear reaction into an aqueous sodium hydroxide solution. Then, the OH group of NaOH in the sodium hydroxide aqueous solution is replaced with 18F, and Na-18F is generated. Na-18F is an ion of Na + and 18F- in an aqueous solution. In other words, any liquid having an OH group that can be substituted with 18F can be used as an RI-labeled compound. Examples of the liquid having an OH group that can be substituted with 18F include alcohols, carboxylic acids, and amino acids.

  Here, the structure of the impurity trap portion 14 is not particularly limited. The impurity trap part 14 is preferably provided with a gas cooling part 14b for cooling the target gas after reaction to 0 degrees or less, for example. Thereby, the target gas after the reaction is cooled to 0 degrees or less, so that the target gas can be reused in the nuclear reaction vessel 10a in a state where the density of the target gas is increased. Moreover, since the target gas after the reaction is likely to contain impurities such as water mixed when bubbling with the liquid compound 13a (for example, liquid having an OH group), such impurities are removed. For this purpose, the target gas is once cooled to 0 degrees or less, whereby the impurities can be liquefied and separated from the target gas. By reliably removing impurities such as water, even if the target gas after removal is returned to the nuclear reaction vessel 10a, impurities such as water do not react with the radioisotope, so that the generation efficiency of the radioisotope Thus, a decrease in the yield of the target RI-labeled compound can be prevented.

  The gas cooling unit 14b includes a fourth supply port 14c to which the reacted target gas exhausted from the exhaust port 13b of the RI labeling compound synthesis unit 13 is supplied, a trap unit 14d for trapping impurities, and the trap unit 14d. Is provided with a cooling medium 14e that cools the gas to 0 degrees or less, a takeout port 14f that takes out impurities below the trap portion 14d, and an exhaust port 14g through which the target gas that has passed through the trap portion 14d is exhausted. For example, the trap part 14d constitutes a detour path for detouring the target gas from the fourth supply port 14c, widens the contact area with the cooling medium 14e, and ensures the liquefaction of impurities.

  As the cooling medium 14e, for example, liquid nitrogen cooled to minus 196 degrees (77K) can be used from the viewpoint of simplicity. Here, when the irradiation unit 12 generates gamma rays using an electron beam of 25 MeV and 1 mA and irradiates neon gas at room temperature for 1 hour, the production amount of 18F corresponding to the amount of the RI-labeled compound for about 2 people is obtained. Can be obtained. If the temperature of the target gas can be cooled to the temperature of liquid nitrogen, the density of the target gas increases, and the generation yield of the radioisotope is the radioisotope when the temperature of the target gas is normal temperature (27 degrees). (273 + 27) /77=3.9 times as much as the production efficiency. In this case, a production amount of 18F corresponding to the amount of RI-labeled compound for about 7-8 persons per hour can be obtained. If the generation of radioisotopes is continued throughout the day, a production amount of 18F corresponding to the amount of RI-labeled compound for 7 people × 24 hours = 168 people can be obtained. Note that the cooling medium 14e is not limited to liquid nitrogen, but may be, for example, methanol containing dry ice. Methanol with dry ice can be cooled to minus 30 degrees.

  By the way, in the above, the impurity trap part 14 employ | adopted the method of liquefying the impurity in target gas by cooling the target gas after reaction, and removing an impurity from target gas, However, Other removal methods are employ | adopted. It doesn't matter. For example, the impurity trap unit 14 may include an impurity adsorption unit that adsorbs water and low-molecular impurities and allows only the target gas to pass therethrough. In the impurity adsorbing part, molecules are adsorbed in porous pores, and the reacted target gas is passed through a molecular sieve (drying agent) that strongly adsorbs water molecules in particular. In addition, the impurity trap unit 14 may include an impurity catalyst unit that reacts the catalyst with impurities to remove the impurities. The catalyst is used in, for example, an exhaust gas purifying apparatus. Thus, other removal methods may be used, and the removal methods may be used alone or in combination.

  Now, the target gas, from which impurities have been removed and exhausted from the exhaust port 14g of the gas cooling unit 14b, is supplied to the first supply port 10e of the compressor and sent out again to the nuclear reaction vessel 10a.

  Here, since the target gas decreases with the synthesis of the RI labeling compound, it is preferable to further include, for example, a gas replenishing unit 16 that replenishes the target gas. As the target gas replenishment position, for example, a first position between the compressor outlet 10b of the gas filling unit 10 and the inlet 10c of the nuclear reaction vessel 10a, the exhaust port 13b of the RI labeling compound synthesis unit 13, and the gas The second position of the cooling unit 14b with the fourth supply port 14c is preferable.

  In the first position, for example, a first gas supply pipe 16a for the target gas is provided between the pressure adjustment valve 10i and the third pressure gauge 10j, and the target gas is replenished by the first gas supply valve 16b. Control is performed. In the second position, a fourth pressure valve 16c is provided between the exhaust port 13b of the RI labeling compound synthesizing unit 13 and the fourth supply port 14c of the gas cooling unit 14b. A second gas supply pipe 16d for target gas is provided between 16c and the exhaust port 13b of the RI labeling compound synthesizing unit 13, and control of replenishment of the target gas by the second gas supply valve 16e and the target used repeatedly Gas expulsion (replacement with a new target gas) is performed. In particular, the target gas replenished by the gas replenishment unit 16 through the second gas supply pipe 16d is once sent through the gas cooling unit 14b to the nuclear reaction vessel 10a. The reaction vessel 10a can be filled. The first gas supply valve 16b and the second gas supply valve 16e are connected to a gas supply port 16f, and a target gas is fed into the gas supply port 16f from a target gas cylinder (not shown).

  In the present invention, when neon gas is used as the target gas, 18F is easily generated using inexpensive neon gas, and a large amount of RI-labeled compounds (for example, Na-18F, 18F-FDG, etc.) substituted with 18F are synthesized. Therefore, RI labeled compounds for PET inspection for several tens of people per day can be manufactured. In the present invention, the neon gas of the raw material can be recovered and reused, and since all can be performed remotely, the possibility of radiation exposure to the operator can be completely eliminated. In addition, since it is not necessary to use expensive 18O concentrated water, it is possible to use PET inspection at a low cost even in developing countries, and medical contributions can be made toward the goal of eradicating human cancer outside the developed countries. In addition, even RI-labeled compounds for drug research can be produced in large quantities.

<Example>
EXAMPLES Hereinafter, although an Example etc. demonstrate this invention concretely, this invention is not limited by this.

  First, based on the drawing shown in FIG. 1, a prototype of the RI-labeled compound production apparatus 1 was created. As shown in FIG. 2, the RI-labeled compound production apparatus 1 includes a gas filling unit 10 of a circulating compressor that fills a nuclear reactor vessel 10a with a neon gas target gas, a gas sealing unit 11 of a pair of pressure valves, The RI labeling compound synthesizing unit 13 having a storing unit 13d for storing glucose and an impurity trap unit 14 for cooling the liquid nitrogen to remove impurities. The radiation irradiation unit 12 is replaced with gamma ray irradiation at a predetermined facility. The RI labeling compound synthesizing unit 13 includes a temperature adjusting unit 13j that keeps the temperature of the storage unit 13d constant.

  As shown in FIG. 3, the first pipe 10d for sending the target gas from the gas filling unit 10 is connected to the inlet 10c of the nuclear reactor 10a, and the first pressure is applied to the inlet 10c of the nuclear reactor 10a. A second pressure valve 11b is provided at each of the valve 11a and the exhaust port 10f of the nuclear reaction vessel 10a. A first pressure gauge 11c is provided between the exhaust port 10f of the nuclear reaction vessel 10a and the second pressure valve 11b. The first pipe 10d is provided with a second pressure gauge 10g, a third pressure valve 10h, and a third pressure gauge 10j. The target gas discharged from the impurity trap part 14 is returned to the compressor by the second pipe 14a. The third pipe 11d connected to the second pressure valve 11b is provided with a fourth pressure gauge 11f between the first pressure gauge 11c and the second supply port 13c of the RI labeling compound synthesizing unit 13. It is done. The reservoir 13d is provided with a supply valve 13h for the liquid compound 13a and a take-out valve 13i for the RI-labeled compound. The trap part 14d is fixed inside the gas cooling part 14b in which liquid nitrogen is put. A fourth pressure valve 16c is provided between the exhaust port 13b of the storage unit 13d and the fourth supply port 14c of the trap unit 14d, and a second pipe 14a is connected to the exhaust port 14g of the trap unit 14d. The A second gas supply pipe 16d is provided between the exhaust port 13b of the reservoir 13d and the fourth pressure valve 16c, and is connected to the gas supply port 16f via the second gas supply valve 16e. The gas supply port 16f is connected to the first gas supply pipe 16a via the first gas supply valve 16b and communicates with the first pipe 10d.

A prototype of this RI-labeled compound production apparatus 1 was carried into an electron beam accelerator (electronic linac) facility, and a production test of 18F was performed. As shown in FIG. 4, the nuclear reaction vessel 10 a of the prototype of the RI-labeled compound production apparatus 1 was placed close to the tip 4 of the electron beam accelerator. Neon gas was sealed in the nuclear reactor 10a as the target gas. The nuclear reaction vessel 10a had a diameter of 2 cm and a length of 50 cm, and neon gas was sealed in the nuclear reaction vessel 10a at 9 atm. Therefore, the volume of neon gas is 3.14 cm ² × 50 cm × 9 atmospheric pressure = 1413 cm ³ , and the amount of neon gas is 1314 cc / 22.4 / 1000 cc = 0.599 mol. Only 10 cc of a low-concentration sodium hydroxide aqueous solution was added as a liquid compound 13a to the reservoir 13d of the RI-labeled compound synthesis unit 13. Liquid nitrogen was put into the impurity trap section 14. Then, tungsten was provided at the tip 4 of the electron beam accelerator, and the electron beam accelerator irradiated the electron beam onto tungsten, and the gamma ray of bremsstrahlung was irradiated onto the nuclear reaction vessel 10a to generate 18F. Then, the nuclear reaction vessel 10a was opened, and the generated neon gas containing 18F was reacted with an aqueous sodium hydroxide solution, and 18F was collected in the aqueous sodium hydroxide solution to produce Na-18F as an RI-labeled compound. The electron beam accelerator had an electron beam energy of 40 MeV, a current value of 3 μA, and a photon flux of 10 ¹² photon / sec. The produced Na-18F was collected in a small bottle, and as shown in FIG. 5, the detection surface of the CdTe detector 5 for radiation detection was applied to the outer surface of the small bottle 6 containing Na-18F, and Na-18F The spectrum of the radiation generated from was measured over time, and the change with time of the spectrum was determined. The analysis of the radiation spectrum was performed by the terminal device 7.

  As shown in FIG. 6, the spectrum of radiation at the completion of the production of Na-18F is represented by a count (count / keV) on the vertical axis and energy (keV) on the horizontal axis, but only a peak with an energy of 511 keV is shown. It is understood that it is seen. This 511 keV peak corresponds to the peak resulting from 18F β + decay. Therefore, it is understood that the manufactured product is approximately Na-18F, and its yield is extremely high.

  In the radiation spectrum shown in FIG. 6, there are two peaks near the energy of 80 keV and one peak near the energy of 180 keV. These peaks are caused by the CdTe detector. Think of things.

Next, the area of the spectrum of the radiation measured at each elapsed time was calculated, and a radiation dose attenuation curve was created. As shown in FIG. 7, the created attenuation curve of the radiation dose is expressed by the total count (count / 10 ³ sec) on the vertical axis and the elapsed time (hour) on the horizontal axis. Here, when the attenuation curve equation is inserted using 109.77 minutes of the half-life of 18F, the attenuation of the radiation dose with time elapses from 2000 (count / 10 ³ sec) to 300 (count / 10 ³ sec). It is understood that it fits the 18F half-life decay curve (the half-life of the decay curve is consistent with the half-life of 18F). This indicates that the manufactured product is approximately 18F. Considering the coincidence between the simplicity of the spectrum of the radiation and the decay curve of the half-life of 18F, it is estimated that the impurities were 1/1000 or less and high-purity Na-18F (RI-labeled compound) was produced.

  Therefore, it was confirmed that the RI-labeled compound production apparatus 1 can produce the RI-labeled compound with an extremely high yield in the prototype.

  Then, the neon gas after irradiation is completely recovered and sealed in the nuclear reactor again. This time, the sodium hydroxide aqueous solution is replaced with liquid glucose, and irradiated with gamma rays to generate 18F. -FDG was produced. The yield at that time was high as described above. Therefore, it was found that the target gas can be reused and the production efficiency of the radioisotope is high. It was also found that the possibility of radiation exposure was close to zero and it could be supplied at a low price.

  As described above, the RI-labeled compound manufacturing apparatus and the RI-labeled compound manufacturing method according to the present invention are useful for all tests using an RI-labeled compound such as a PET test and a SPECT test, and are not limited to medical use but for research purposes. It can be used for the production of RI-labeled compounds used in various industries such as industrial use and food. In addition, the RI labeled compound production apparatus and the RI labeled compound are capable of reusing the target gas, have high production efficiency of radioisotopes, bring the possibility of radiation exposure close to zero, and can be supplied at a low price. It is effective as a manufacturing method.

DESCRIPTION OF SYMBOLS 1 RI labeling compound manufacturing apparatus 10 Gas filling part 11 Gas sealing part 12 Radiation irradiation part 13 RI labeling compound synthesis part 14 Impurity trap part 14b Gas cooling part 15 Circulation cooling part 16 Gas replenishment part

As a result of intensive studies, the present inventor has completed the novel RI-labeled compound manufacturing apparatus and RI-labeled compound manufacturing method according to the present invention. That is, the present invention is an RI-labeled compound manufacturing apparatus for manufacturing an RI-labeled compound, and includes a gas filling unit, a gas sealing unit, a radiation irradiation unit, an RI-labeled compound synthesis unit, and an impurity trap unit. Gas filling unit, a neon gas filled in the nuclear reactor, the gas seal seals the nuclear reactor the neon gas-filled. Irradiation section, the neon gas gamma is irradiated predetermined time nuclear reactor sealed is, the neon gas is nuclear reaction. RI labeled compound synthesis unit, after opening of the nuclear reactor, the radioactive isotopes contained in the neon gas after the nuclear reaction is reacted with a compound of liquid having a substitutable OH groups and 18F, 18F labeled compound Is synthesized. Impurity trap section, to remove impurities from the neon gas after the reaction to return the neon gas after the removal to the nuclear reactor.

The present invention is also an RI labeled compound manufacturing method for manufacturing an RI labeled compound, comprising a gas filling step, a gas sealing step, a radiation irradiation step, an RI labeled compound synthesis step, and an impurity trap step. Gas filling step, a neon gas filled in the nuclear reactor, the gas sealing step seals the nuclear reactor the neon gas-filled. Irradiation step, the neon gas gamma is irradiated predetermined time nuclear reactor sealed is, the neon gas is nuclear reaction. RI labeled compound synthesis step, after opening of the nuclear reactor, the radioactive isotopes contained in the neon gas after the nuclear reaction is reacted with a compound of liquid having a substitutable OH groups and 18F, 18F labeled compound Is synthesized. Impurity trap step to remove impurities from the neon gas after the reaction to return the neon gas after removal to the nuclear reactor.

As a result of intensive studies, the present inventor has completed the novel RI-labeled compound manufacturing apparatus and RI-labeled compound manufacturing method according to the present invention. That is, the present invention is an RI-labeled compound manufacturing apparatus for manufacturing an RI-labeled compound, and includes a gas filling unit, a gas sealing unit, a radiation irradiation unit, an RI-labeled compound synthesis unit, and an impurity trap unit. The gas filling unit fills the nuclear reaction container with neon gas, and the gas sealing unit seals the nuclear reaction container filled with the neon gas. The radiation irradiation unit irradiates the nuclear reaction container sealed with the neon gas with gamma rays for a predetermined time to cause the neon gas to undergo a nuclear reaction. After opening the nuclear reaction vessel, the RI-labeled compound synthesis unit reacts ¹⁸ F contained in the neon gas after the nuclear reaction with a liquid compound having an OH group capable of substituting for ¹⁸ F , whereby the ¹⁸ F- labeled compound Is synthesized. The impurity trap section removes impurities from the neon gas after the reaction, and returns the neon gas after the removal to the nuclear reaction vessel.

The present invention is also an RI labeled compound manufacturing method for manufacturing an RI labeled compound, comprising a gas filling step, a gas sealing step, a radiation irradiation step, an RI labeled compound synthesis step, and an impurity trap step. The gas filling step fills the nuclear reaction vessel with neon gas, and the gas sealing step seals the nuclear reaction vessel filled with the neon gas. In the radiation irradiation step, the neon gas is irradiated with gamma rays for a predetermined time to cause a nuclear reaction of the neon gas. In the RI-labeled compound synthesis step, after opening the nuclear reaction vessel, ¹⁸ F contained in the neon gas after the nuclear reaction is reacted with a liquid compound having an OH group capable of substituting with ¹⁸ F , whereby ¹⁸ F- labeled compound Is synthesized. In the impurity trap step, impurities are removed from the neon gas after the reaction, and the neon gas after the removal is returned to the nuclear reaction vessel.

Claims (6)

An RI-labeled compound manufacturing apparatus for manufacturing an RI-labeled compound,
A gas filling unit for filling the target gas into the nuclear reactor;
A gas sealing part for sealing the nuclear reaction vessel filled with the target gas;
Radiation irradiation unit for irradiating a nuclear reaction container sealed with the target gas for a predetermined time, and nuclear reaction of the target gas;
An RI-labeled compound synthesizer for synthesizing an RI-labeled compound by reacting a radioactive isotope contained in the target gas after the nuclear reaction with a liquid compound after the nuclear reaction vessel is opened;
An impurity trap part for removing impurities from the target gas after the reaction and returning the target gas after the removal to the nuclear reaction vessel;
RI-labeled compound synthesizer comprising: The target gas is neon gas,
The radiation is gamma rays;
The RI-labeled compound synthesizer according to claim 1, wherein the compound is a liquid having an OH group that can be substituted with 18F. The RI-labeled compound synthesizing apparatus according to claim 1 or 2, wherein the pressure of the target gas filled in the nuclear reaction vessel is higher than normal pressure. The radiation irradiator is
An electron beam irradiation unit that is an electron beam accelerator that irradiates an electron beam having a predetermined energy;
A gamma-ray emitting unit that is provided in the vicinity of the nuclear reaction vessel, is composed of a target containing tungsten, and emits gamma rays when irradiated with an electron beam;
The RI-labeled compound synthesizer according to any one of claims 1 to 3. The impurity trap portion is
The RI labeling compound synthesizing apparatus according to any one of claims 1 to 4, further comprising: a gas cooling unit that cools the target gas after the reaction to 0 degrees or less. An RI labeled compound manufacturing method for manufacturing an RI labeled compound,
A gas filling step of filling the target gas into the nuclear reactor;
A gas sealing step for sealing the nuclear reaction vessel filled with the target gas;
Radiation irradiation step of irradiating a nuclear reaction container sealed with the target gas for a predetermined time and causing the target gas to undergo a nuclear reaction, and
An RI-labeled compound synthesis step for synthesizing an RI-labeled compound by reacting a radioisotope contained in the target gas after the nuclear reaction with a liquid compound after the nuclear reaction vessel is opened;
An impurity trap step of removing impurities from the target gas after the reaction and returning the target gas after the removal to the nuclear reaction vessel;
An RI-labeled compound synthesis method comprising: