CN111574316A

CN111574316A - Method and apparatus for producing RI-labeled compound

Info

Publication number: CN111574316A
Application number: CN202010349468.7A
Authority: CN
Inventors: 高桥成人
Original assignee: Hiking Group Co Ltd
Current assignee: Hiking Group Co Ltd
Priority date: 2020-04-28
Filing date: 2020-04-28
Publication date: 2020-08-25
Also published as: CN112898107A

Abstract

The invention belongs to the field of RI labeled compound manufacturing, and particularly relates to a manufacturing method and a manufacturing device for manufacturing RI labeled compound; the manufacturing method provided by the invention comprises a gas filling step, a gas sealing step, a radioactive ray irradiation step, an RI labeled compound synthesis step and a mass separation step; the manufacturing apparatus provided by the present invention comprises a gas filling part, a gas sealing part, a radiation irradiating part, an RI-labeled compound synthesizing part, and an impurity separating part; the present invention can realize the reuse of target gas, lower the production cost, raise the production efficiency of radioactive isotope, lower the possibility of radiation damage and realize low cost supply.

Description

Method and apparatus for producing RI-labeled compound

Technical Field

The invention belongs to the field of RI labeled compound manufacturing, and particularly relates to a manufacturing method and a manufacturing device for manufacturing RI labeled compound.

Background

In recent years, Positron Emission Tomography (PET) examination and Single Photon Emission Computed Tomography (SPECT) examination are the most widely used 2 cancer diagnosis methods in the world today.

According to the report of the national center for cancer research of 2016, 7, 15: in 2015, 37 million people died from cancer in japan, and by 2016, it is expected that newly diagnosed cancer patients will reach 101 million people. In japan, where the medical system is sound, cancer mortality is still high compared to europe and america, and therefore PET and SPECT are frequently used for cancer diagnosis.

In both PET examination and SPECT examination, a radioisotope-labeled compound (RI-labeled compound) is basically used. RI-labeled compounds are compounds that are distinguished from conventional compounds by replacing the atom at a specific position of the compound that is readily absorbed by the tumor nest with a Radioactive Isotope (RI). The RI-labeled compound commonly used in PET examination is prepared by labeling 18-fluoro isotope (¹⁸F) Formed by labelling on glucose¹⁸F-2-fluoro-2-deoxy-D-glucose (abbreviated as¹⁸F-FDG), after ingestion of the medicament by the patient, due to¹⁸In F-FDG¹⁸The positron emitted from F collides with an electron and annihilates, and 2 gamma rays with 511keV energy are generated, and the gamma rays can be detected to be directed to the inside of the body¹⁸The distribution of F-FDG was photographed to identify a tumor lesion with a significant abnormality in glucose metabolism. On the other hand, an RI-labeled compound used in SPECT examination is a (99 mTc) labeled compound in which a 99 mtec isotope capable of emitting gamma rays is combined, and after a patient takes a drug, the distribution of 99mTc in the body can be imaged by detecting gamma rays having an energy of 140keV emitted from 99 mTc. Since the 99mTc labeled compound can be absorbed by blood, it is generally used for imaging cardiovascular and cerebrovascular functions in SPECT examination.

However, both PET and SPECT examinations use specific RI-labeled compounds, and thus the examination cost is high. For example, in 2007, patients who received SPECT examination all over Japan have over 100 million persons, and the total cost is as high as 1500 billion yen, and the cost of 99mTc accounts for nearly 100%. The cost required for PET examination is more than 3-4 times that of SPECT examination. That is, in Japan, the imaging diagnosis such as PET and SPECT examinations necessary for the diagnosis of cancer is required to cost several billions of yen each year.

Used in PET examination¹⁸F-FDG is generally produced as follows: first of all using a compact cyclotron to produceProton beam pair of 18-oxygen isotope(s) (ii)¹⁸0) Performing irradiation with¹⁸0 (p, n) 18F reaction from 18O¹⁸F。

Among them, 16-oxygen isotope (¹⁶0) 99.762% of the total content, 0.039% of the content of 17-oxygen isotope, and 18-oxygen isotope(s) (ii)¹⁸0) Accounting for only 0.201%. Thus, in the manufacture for PET examinations¹⁸In case of F, expensive heavy oxygen water is often used. For example, Japanese patent laid-open publication No. 2004-59356 (patent document 1) discloses the production as¹⁸The heavy oxygen water of the F fluoride ion raw material. The use of heavy oxygen water is not mastered by most developing countries because heavy oxygen water is too expensive.

In addition, it is manufactured by using a compact cyclotron¹⁸At F, the likelihood of radiation injury to the associated personnel has been high. That is, the production by irradiating heavy oxygen water with a high intensity proton beam generated by a compact cyclotron¹⁸During the process F, a large amount of radioactive substances are inevitably generated at the lead-out port of the proton beam, and the lead-out port is easily damaged for a long time, so that the lead-out port needs to be replaced regularly and the irradiation device of the proton beam needs to be overhauled regularly; the above work necessarily causes radiation hazard.

For the above reasons, in recent years, various researchers have been working on development of water generation without using heavy oxygen¹⁸And F. For example: japanese patent laid-open Nos. 2004-59356 (patent document 1), 2006-3363 (patent document 2), 2010-164477 (patent document 3), and the like; among them, Japanese laid-open patent publication No. 2006-3363 (patent document 2) discloses the use of a catalyst containing¹⁸0 gas efficiently producing a catalyst containing¹⁸F, fluorine gas. Japanese patent application laid-open No. 2010-16447 (patent document 3) discloses a technique for producing a radioactive gas isotope from a target gas; the method is technically characterized in that gas filled in a reaction chamber is circulated and cooled in the nuclear reaction, so that the pressure in the reaction chamber is kept at a low value, and the thickness of an emission opening through which a charged particle beam passes is further reduced.

However, the patent documents mentioned above propose¹⁸F in the manufacturing technology of the sameThe use of expensive high concentrations is necessary¹⁸0 isotope of and¹⁸f yield was also low. In addition, because¹⁸The fabrication of F requires the use of a high intensity proton beam generated by a compact cyclotron, and therefore presents the problem of difficulty in reducing the radiation hazard.

Therefore, how to reduce the manufacturing cost of RI-labeled compounds, improve the manufacturing efficiency, and minimize the possibility of radiation damage becomes a problem to be solved in the prior art.

Disclosure of Invention

In order to solve the above-mentioned technical problems, the present invention aims to provide a method for producing an RI-labeled compound, which is low in production cost, high in production efficiency, and small in radiation damage; another object of the present invention is to provide an apparatus for producing an RI-labeled compound, which realizes the production method.

In order to achieve the purpose, the invention adopts the technical scheme that: an RI-labeled compound production apparatus for producing an RI-labeled compound, which comprises a gas filling portion for filling a target gas into a nuclear reaction vessel, a gas sealing portion for sealing the nuclear reaction vessel filled with the target gas, a radiation irradiating portion for irradiating the inside of the nuclear reaction vessel sealed with the target gas with radiation for a predetermined time to cause the target gas to generate a nuclear reaction, an RI-labeled compound synthesizing portion for synthesizing the RI-labeled compound by reacting the compound with the target gas containing a radioisotope after the radiation irradiation, and an impurity separating portion for separating impurities in the target gas after the reaction with the compound and returning the target gas after the impurities are separated to the nuclear reaction vessel.

Preferably, in the RI-labeled compound synthesizing apparatus, the target gas is neon,

the radiation is gamma ray, and the RI-labeled compound is 18F-FDG.

Preferably, in the RI-labeled compound synthesizing apparatus, the target gas filled in the nuclear reaction vessel has a pressure higher than a standard pressure.

Preferably, in the RI-labeled compound synthesizing apparatus, the radiation irradiating section includes an electron beam irradiating section of an electron linear accelerator capable of irradiating an electron beam of a rated energy when the radiation is a gamma ray; a gamma ray emitting part which is arranged beside the nuclear reaction vessel and is provided with a target containing tungsten and can generate gamma rays after being irradiated by electron beams.

Preferably, the impurity separation section includes a cooling section for cooling the target gas after the reaction with the compound to 0 ℃ or lower.

The invention provides an RI-labeled compound manufacturing method for manufacturing RI-labeled compounds, which comprises the following specific steps: a gas filling step of filling target gas into the nuclear reaction vessel; a gas sealing step of sealing the nuclear reaction vessel filled with the target gas; a radiation irradiation step of irradiating the inside of a nuclear reaction vessel in which the target gas is sealed with radiation for a predetermined time to cause nuclear reaction of the target gas; an RI-labeled compound synthesis step of synthesizing an RI-labeled compound by reacting the compound with the target gas containing the radioisotope after the irradiation with the radiation; and an impurity separation step of separating impurities in the target gas after the reaction with the compound and returning the target gas after the separation of the impurities to the nuclear reaction vessel.

The method and apparatus for producing RI-labeled compounds provided in the present specification are only an example under the claims of the present invention, and the technical solution provided in the present invention includes not only the steps and structures described in the present specification, but also similar, other, steps and structures that are consistent with the idea, concept, purpose and function of the present invention, can achieve the recycling of target gas, reduce the production cost, improve the production efficiency of radioisotopes, and minimize the possibility of radiation damage.

The present inventors have conducted extensive studies to confirm that a completely new apparatus and method for producing an RI-labeled compound have been accomplished. That is, the present invention is an RI-labeled compound manufacturing apparatus for manufacturing an RI-labeled compound, including a gas filling portion, a gas sealing portion, a radiation irradiating portion, an RI-labeled compound synthesizing portion, and an impurity separating portion. Wherein the gas filling part mainly functions to fill the target gas into the nuclear reaction vessel, and the gas sealing part mainly functions to seal the nuclear reaction vessel filled with the target gas. The radiation irradiating section mainly functions to irradiate radiation into the nuclear reaction vessel in which the target gas is sealed for a predetermined time to promote nuclear reaction of the target gas. The main function of the RI-labeled compound synthesis part is to react the radioisotope contained in the target gas after irradiation with radiation with the compound to produce an RI-labeled compound and thus an RI-labeled compound. The main function of the impurity separating section is to separate impurities in the target gas after reaction with the compound and to return the target gas after separation of impurities to the aforementioned nuclear reaction vessel.

In addition, the present invention, as a brand new method for preparing RI-labeled compounds, is divided into the steps of gas filling, gas sealing, radiation irradiation, RI-labeled compound synthesis, impurity separation, and the like. Wherein the gas filling step is to fill the target gas into the nuclear reaction vessel, and the gas sealing step is to seal the target gas in the nuclear reaction vessel. The radiation irradiation step is a step of irradiating the inside of the nuclear reaction vessel in which the target gas is sealed with radiation for a predetermined time to promote nuclear reaction of the target gas. The RI-labeled compound synthesis step is a step of reacting a compound with a radioisotope contained in the target gas after the nuclear reaction to produce an RI-labeled compound. The impurity separation step is to separate impurities in the target gas after the reaction with the compound and to return the target gas from which the impurities have been separated to the nuclear reaction vessel.

Briefly, the present invention relates to a manufacturing apparatus and a manufacturing method relating to RI-labeled compounds; the gas filling portion 10 is responsible for filling the target gas into the nuclear reaction vessel 10a, and the gas sealing portion 11 is responsible for sealing the aforementioned target gas inside the nuclear reaction vessel 10 a. The radiation irradiating section 12 is responsible for irradiating radiation into the nuclear reaction vessel 10a in which the target gas is sealed for a set time to promote nuclear reaction of the target gas. The main function of the RI-labeled compound synthesizing section 13 is to react the radioisotope contained in the target gas after the nuclear reaction with the compound 13a, thereby producing an RI-labeled compound. The impurity separating section 14 has a main function of separating impurities in the target gas after the reaction with the aforementioned compound 13a and reintroducing the target gas after the separation of impurities into the nuclear reaction vessel 10 a.

The invention has the beneficial effects that: the present invention can realize the reuse of target gas, lower the production cost, raise the production efficiency of radioactive isotope, lower the possibility of radiation damage and realize low cost supply.

Drawings

FIG. 1 is a schematic view of an apparatus for producing an RI-labeled compound according to the present invention;

FIG. 2 is a diagram of an apparatus for manufacturing RI labeled compounds according to the present invention;

FIG. 3 is a front view of an RI-labeled compound manufacturing apparatus in the case of practical arrangement of the present invention;

FIG. 4 is a side view of an apparatus for producing an RI-labeled compound according to an actual embodiment of the present invention.

1. An RI-labeled compound production apparatus;

10. a gas-filled portion; 10a, a nuclear reaction vessel; 10b, a delivery outlet of the gas filling portion 10; 10c, an inlet of the nuclear reaction vessel 10 a; 10d, a first pipeline; 10e, a first supply port of the compression device of the gas filling portion 10; 10f, an exhaust port of the nuclear reaction vessel 10 a; 10g, a second pressure gauge; 10h, a third pressure valve; 10i, a pressure regulating valve; 10j, a third pressure gauge;

11. a gas seal portion; 11a, a first pressure valve; 11b, a second pressure valve; 11c, a first pressure gauge; 11d, a third pipeline; 11e, a pressure reducing valve; 11f, a fourth pressure gauge;

12. a radiation irradiating section; 12a, an electron beam irradiation section; 12b, a gamma ray generating section;

13. an RI-labeled compound synthesis moiety; 13a, a compound which reacts with a radioisotope contained in the target gas after the nuclear reaction; 13b, vent of the RI-labeled compound synthesizing portion 13; 13c, second supplyA mouth; 13d, a storage portion for liquid glucose; 13e, a mixing section; 13f, a third supply port; 13g of,¹⁸An outlet for F-FDG; 13h, a supply valve responsible for controlling the supply of liquid glucose; 13i, responsible for controlling the removal of synthesized¹⁸A take-off valve for F-FDG; 13j, a temperature adjusting section for adjusting the temperature of the storage section 13 d;

14. an impurity separation section; 14a, a second pipeline; 14b, a gas cooling section; 14c, a fourth supply port; 14d, a separation section responsible for separating impurities; 14e, a refrigerant; 14f, a take-out port for taking out the impurities; 14g, an exhaust port responsible for exhausting the target gas passing through the separation portion 14 d;

15 circulating cooling part;

16 gas make-up portion; 16a, a first gas supply pipe; 16b, a first gas supply valve; 16c, a fourth pressure valve; 16d, a second gas supply pipe; 16e, a second gas supply valve; 16f, gas supply port.

Detailed Description

For understanding the present invention, embodiments of the present invention are explained below with reference to the drawings. It is to be emphasized that the following embodiment is merely an example of the case of the actual arrangement of the present invention, and does not mean that the technical scope of the present invention is limited only to the case of the actual arrangement described below.

As shown in FIG. 1, the present invention is an RI-labeled compound manufacturing apparatus 1 for manufacturing an RI-labeled compound, which includes a gas filling portion 10, a gas sealing portion 11, a radiation irradiating portion 12, an RI-labeled compound synthesizing portion 13, and an impurity separating portion 14.

The gas filling portion 10 is responsible for filling the target gas into the nuclear reaction vessel 10a, and the gas sealing portion 11 is responsible for sealing the nuclear reaction vessel 10a filled with the target gas. The radiation irradiating section 12 is responsible for irradiating radiation into the nuclear reaction vessel 10a in which the target gas is sealed for a set time to promote nuclear reaction of the target gas. The main function of the RI-labeled compound synthesizing section 13 is to react the radioisotope contained in the target gas after the nuclear reaction with the compound 13a, thereby producing an RI-labeled compound. The main function of the impurity separating section 14 is to separate impurities in the target gas after the reaction with the compound 13a and to return the target gas after the separation of impurities to the aforementioned nuclear reaction vessel 10 a.

The present invention promotes nuclear reaction of target gas by irradiation with radioactive rays, and after producing radioactive isotopes, the target gas containing the radioactive isotopes is directly reacted with a compound 13 a. Therefore, simultaneous synthesis of the radioisotope and the RI-labeled compound in the same apparatus can be achieved, and the radioisotope can be directly converted into the RI-labeled compound after production, thereby improving the production efficiency of the RI-labeled compound.

Impurities are generated in the target gas after the RI-labeled compound synthesis reaction, and the target gas after the impurities are separated and reused, so that the RI-labeled compound synthesis efficiency can be improved and the RI-labeled compound can be supplied at a lower cost. In particular, the target for manufacturing the radioactive isotope in the invention is changed from original liquid to gas, so that the target is easy to transport and use; and the target gas after the nuclear reaction can be conveniently and simply conveyed back to the nuclear reaction vessel 10a to form a complete cycle process. If a liquid target is used, the liquid target is decomposed by irradiation of radioactive rays with generation of radioactive isotopes, and bubbles are generated in the liquid target, which makes it difficult to transfer the target liquid after nuclear reaction.

In addition, the present invention can be controlled by a computer regardless of the circulation of the target gas or the continuous production of the radioisotope for the synthesis of the RI-labeled compound. That is, the various components of the present invention can be controlled automatically, and thus the RI-labeled compound can be obtained by a remote operation. The operator can be out of contact with the manufacturing device, reducing the radiation risk.

In the present invention, the kind of the target gas and the kind of the radiation are not particularly limited, and can be selected by design according to the RI-labeled compound required. For example, if the RI-labeled compound produced is¹⁸In the case of F-FDG, neon gas may be selected as the target gas, and gamma gas may be selected as the radiationNeon is a rare gas element which hardly reacts with other atoms and molecules and is inexpensive, and on the other hand, neon irradiated with gamma rays can be indirectly obtained by β decay after 20Ne (γ, 2 n) 18Ne reaction¹⁸F, or directly produced by a reaction of 20Ne (gamma, pn) 18F¹⁸F. In addition, since the nuclear reactions are all the photonuclear reactions, the generation of unnecessary radioactive substances is also drastically reduced. The neon gas irradiated with the radioactive rays can be used to completely recycle the target while suppressing the generation of unnecessary radioactive substances. And simultaneously, expensive heavy oxygen water is not used, so that the 18F can be supplied at low cost.

The gas-filled portion 10 also has no particular requirement in configuration. Generally, a circulation type compressor capable of circulating the target gas can be used. In this case, a first pipeline 10d communicating with each other may be provided between the outlet 10b of the compressing device for transporting the target gas and the inlet 10c of the nuclear reaction vessel 10 a. In addition, after impurities are removed from the reacted target gas discharged from the exhaust port 13b of the RI-labeled compound synthesizing section 13 by the impurity separating section 14, the target gas from which the impurities have been separated is supplied to the first supply port 10e of the compression device of the gas filling section 10 by using the second pipe 14a, and the circulation of the target gas can be realized very easily.

The nuclear reactor vessel 10a has no particular structural requirement. In general, materials with better thermal conductivity can be used. Specifically, a silicon carbide ceramic container having a thermal conductivity comparable to that of copper can be used, so that even if the container generates heat by absorbing radiation such as gamma rays, the heat can be rapidly dissipated, thereby preventing an excessive pressure in the container. Of course, even if the target gas does not belong to the compressed gas (gas having a pressure of 10MPa or more at normal temperature) specified in "high pressure gas Standard method", the RI-labeled compound can be synthesized. In addition, silicon carbide and¹⁸f does not react chemically and thus can be guaranteed to be formed¹⁸The purity of F. In addition, if the problem of the corrosiveness of fluorine generated in the synthesis is taken into consideration, the inner surface of the container can be coated with a corrosion-resistant Teflon materialCoating the surface. A circulating cooling part 15 for circulating a coolant such as liquid nitrogen may be additionally installed outside the nuclear reaction vessel 10a for cooling.

The gas-tight section 11 has no particular structural requirement. Generally, the reactor may include a first pressure valve 11a connected to the inlet 10c of the nuclear reactor 10a, a second pressure valve 11b connected to the outlet 10f of the nuclear reactor 10a, and a first pressure gauge 11c disposed between the exhaust pipe 10f and the second pressure valve 11 b. When the gas filling portion 10 fills the target gas into the nuclear reaction vessel 10a, the gas sealing portion 11 opens the first pressure valve 11a and closes the second pressure valve 11b, and detects the pressure value of the first pressure gauge 11c and fills the target gas into the nuclear reaction vessel 10a according to the set pressure requirement. Subsequently, after the first pressure gauge 11c reaches the set pressure value, the gas sealing part 11 closes the first pressure valve 11a and seals the nuclear reaction vessel 10 a. The gas sealing portion 11 can also check whether there is an abnormality by monitoring the first pressure gauge 11 c. During the irradiation of the radiation, the gas sealing portion 11 keeps the first pressure valve 11a and the second pressure valve 11b in the closed state while the target gas in the nuclear reaction vessel 10a performs the nuclear reaction and generates the radioisotope. After the irradiation of the radioactive rays is stopped, the gas sealing portion 11 opens the second pressure valve 11b to discharge the target gas after the nuclear reaction in the nuclear reaction vessel 10 a.

The pressure of the target gas filled in the nuclear reaction vessel 10a is not particularly limited. Generally, higher pressures are recommended than standard pressures. In the present invention, the gas target is irradiated with radioactive rays, and the efficiency of producing radioisotopes is lower than that of using a liquid target. In response to such a deficiency, the efficiency of radioisotope production can be significantly improved by measures such as increasing the pressure of the target gas in the nuclear reaction vessel 10a and decreasing the temperature. The target gas pressure in the nuclear reaction vessel 10a may not be within the compressed gas range specified in "high pressure gas specification". In general, the pressure can be set between 3MPa and 10 MPa. In addition, the pressure of the target gas in the nuclear reaction vessel 10a is increased, which is advantageous in that the target gas after the nuclear reaction can be smoothly discharged when the second pressure valve 11b is opened.

A first pipe 10d is provided between the outlet 10b of the gas filling portion 10 and the inlet 10c of the nuclear reaction vessel 10a, and a second pressure gauge 10g, a third pressure valve 10h, a pressure regulating valve 10i, and a third pressure gauge 10j are provided in this order from the outlet 10b in addition to the first pressure valve 11 a. The second pressure gauge 10g is used to measure the pressure of the target gas between the delivery port 10b and the third pressure valve 10 h. The third pressure valve 10h is used to control the delivery of the target gas from the delivery port 10b of the gas filling portion 10. The pressure regulating valve 10i can adjust the pressure level in the case where the pressure of the target gas delivered by the third pressure valve 10g is too high. The third pressure gauge 10j is used to measure the pressure of the target gas between the pressure regulating valve 10i and the first pressure valve 11 a.

The radiation irradiating section 12 has no particular structural requirement. Generally, when gamma rays are used as the radiation, the gamma ray generating section 12b is provided near the nuclear reactor 10a and emits gamma rays when irradiated with electron beams, and includes an electron beam irradiating section 12a having a rated power and emitting electron beams. With this design, gamma ray irradiation can be easily performed. Wherein, the gamma ray generating part 12b can select the target (such as tungsten, platinum, tantalum, etc.) irradiated by the electron beam to generate the gamma ray according to the requirement. Specifically, gamma rays of bremsstrahlung can be generated and utilized by irradiating tungsten with an electron beam of 30MeV energy.

In the case where heavy oxygen water is irradiated with a proton beam, nuclear reaction occurs due to strong nuclear force, and thus the extraction port is irradiated with high intensity radiation. In contrast, in the case of gamma rays of bremsstrahlung generated by irradiating a target with an electron beam, the target window is made of silicon or carbon, and the half-life of the residual radioactive substance generated by the photonuclear reaction is only several milliseconds, and practically no radioactive compound substance is generated. In addition, since no radioactive compound remains for a long time, the target apparatus does not need to be replaced. Therefore, the present invention can also reduce the possibility of radiation damage from this point.

The Electron beam irradiating section 12a may generally use an Electron linear accelerator (Electron linear accelerator), and can easily realize full automation and remote operation. Proton beams for cyclotrons require the operator to have knowledge and familiarity with the relevant procedures, but electron linacs have the advantage that novices can quickly gain access. In addition, the cyclotron requires periodic equipment replacement, and a large amount of cost is required to treat radioactive substances generated from the cyclotron, and an electron linear accelerator that hardly generates radioactive compounds is also very advantageous from the viewpoint of waste treatment.

Further, since not a proton beam of a cyclotron but a gamma ray is used, the nuclear reaction vessel 10a (target) can be manufactured as thick as possible. For example, the proton beam irradiation using a cyclotron is used for heavy oxygen water production¹⁸F, i.e. by using¹⁸0（p，n）¹⁸In the case of the F reaction, the energy of the proton beam is 15MeV and the current is between 50mA and 70 mA. In addition, the proton beam also needs to pass from the cyclotron into the atmosphere through an extraction port, and the proton beam also needs to pass through a target window of a container containing the target. Among these, the maximum distance that can be reached by a proton beam of 15MeV, and heavy oxygen water is about 6mm or so. If it is desired to be able to generate radioisotopes, it is also necessary to increase the current of the proton beam that irradiates the target. Therefore, both the extraction port and the target window are damaged by high-intensity radiation generated from the proton beam to the extraction port and the target window, and therefore, the extraction port and the target window generally need to be replaced every 2 weeks. Such replacement is not only complicated to operate but also highly vulnerable to radiation injury to the operator. The invention selects gamma ray, which is generated by electron linear accelerator, to reduce the damage of radiation. Further, as gamma rays having extremely high penetrating power, a target having a thickness of 20cm can be penetrated even at an extremely low temperature of 4K. In practical operation, gamma rays are used for irradiating neon gas at normal temperature, and RI labeled compounds equivalent to those used for PET detection can be generated every 1 hour¹⁸F-FDG2 parts by weight¹⁸F。

Further, with respect to radiation irradiationThe specific time of the method has no special requirements. In general, it is recommended to set the irradiation time to half the half-life period required for generation of the radioisotope. For example, the radioisotope is¹⁸F is due to¹⁸F has a half-life of 110 minutes, the irradiation time can be set to 55 minutes accordingly.

When the radiation irradiation section 12 stops the irradiation of the radiation and the gas sealing section 11 opens the second pressure valve 11b, the target gas after the nuclear reaction is discharged from the nuclear reaction vessel 10a and is sent to the RI labeled compound synthesizing section 13.

Wherein, between the second pressure valve 11b and the second supply port 13c of the RI labeled compound synthesizing portion 13, a third piping 11d communicating with each other is provided; a pressure reducing valve 11e and a fourth pressure gauge 11f are provided in the third pipe line 11d in this order from the second pressure valve 11 b. The pressure reducing valve 11e is responsible for reducing the pressure in case the target gas pressure is too high after the second pressure valve 11b is opened. The fourth pressure gauge 11f is responsible for measuring the pressure of the target gas between the pressure reducing valve 11e and the second common port 13c of the RI-labeled compound synthesizing portion 13.

The RI-labeled compound synthesizing moiety 13 has no particular structural requirement, and generally, the radioisotope is defined as¹⁸F. RI labeled compounds of¹⁸In the case of F-FDG, the RI-labeled compound synthesizing section 13 includes a storage section 13d for storing liquid glucose as the compound 13a, and a mixing section 13e communicating with the second supply port 13c for mixing the liquid glucose with the target gas after the nuclear reaction. Thus, by mixing the target gas after the nuclear reaction with liquid glucose, the radioisotope contained in the target gas is produced¹⁸F reacts with glucose and can be synthesized very simply¹⁸F-FDG. In addition, when the target gas is neon, since neon has a low reactivity, it does not undergo a nuclear reaction and can smoothly pass therethrough even when mixed with glucose, thereby realizing the recycling of neon.

The RI-labeled compound synthesizing section 13 is provided with a third supply port 13f for supplying liquid glucose above the reservoir section 13d and a discharge port for discharging the synthesized RI-labeled compound below the reservoir section 13d¹⁸The outlet 13g of F-FDG can conveniently supply liquid glucose and¹⁸and (4) taking out F-FDG. The third supply port 13f is provided with a supply valve 13h for controlling the supply of liquid glucose, and the discharge port 13g is provided with a valve for controlling the discharge of the synthesized glucose¹⁸And a take-out valve 13i for F-FDG. The RI-labeled compound synthesizing portion 13 may also be provided with a temperature adjusting portion for maintaining the temperature of the storage portion 13d as necessary.

In addition, the target gas from which the radioactive isotope is lost after being mixed with the liquid glucose may be discharged through the exhaust port 13b of the RI-labeled compound synthesizing portion 13 and input to the first supply port 10e of the gas filling portion 10 through the second pipe 14a of the impurity separating portion 14.

The impurity separating section 14 has no particular structural requirement. Generally, it is recommended to provide a gas cooling section 14b for cooling the target gas after the reaction to 0 degree or less at the impurity separating section 14. The density of the target gas can be increased by cooling and fed into the nuclear reaction vessel 10a for reuse. In addition, impurities such as water and the like are easily mixed in the target gas after reaction through mixing with liquid glucose; impurities can also be liquefied and separated from the target gas by cooling. The target gas from which impurities such as water are surely separated is returned to the nuclear reaction vessel 10a, so that the radioactivity can be maintained

The efficiency of isotope production prevents the efficiency of RI-labeled compound synthesis from lowering.

The gas cooling section 14b includes a fourth supply port 14c responsible for supplying the reacted target gas discharged from the exhaust port 13b of the RI-labeled compound synthesizing section 13, a separation section 14d responsible for separating impurities, a refrigerant 14e responsible for cooling the separation section 14d to 0 degrees or less, a take-out port 14f located below the separation section 14d for taking out impurities, and an exhaust port 14g responsible for discharging the target gas passing through the separation section 14 d. The separation portion 14d generally bypasses the target gas from the fourth supply port 14c to increase the contact area with the refrigerant agent 14e, thereby ensuring that the impurities can be liquefied.

For ease of operation, the refrigerant 14e may be optionally cooled to-196 deg.CLiquid nitrogen in degree (77K). The radiation irradiating section 12 generates gamma rays using an electron beam of 25MeV and 1mA, and irradiates neon gas at normal temperature to generate RI-labeled compounds equivalent to those used for PET detection every 1 hour¹⁸F-FDG2 parts by weight¹⁸F. If the temperature of the target gas is cooled to the liquid nitrogen temperature, the density of the target gas is increased, and the generation efficiency of the radioisotope can be increased by (273 + 27)/77 =3.9 times as compared with the generation efficiency at normal temperature (27 degrees). In this case, an amount of 7 to 8 parts by weight of RI-labeled compound used for PET detection may be generated every 1 hour¹⁸F. Given that radioisotope synthesis can be continued, an RI-labeled compound equivalent to that used for PET detection can be produced every 1 day¹⁸F-FDG7 human × 24 with 24 hours =168 number of human shares¹⁸F. Further, if the refrigerant 14e is not limited to liquid nitrogen, the cooling temperature of methanol containing dry ice may be-30 ℃.

However, the impurity separating section 14 may employ other separation methods in addition to the above-described method of liquefying the impurities contained in the target gas by cooling the target gas. For example, the impurity separation section 14 may be provided with an impurity adsorbing section capable of adsorbing water and small-molecule impurities and allowing only the target gas to pass therethrough. The impurity adsorbing portion may adsorb molecules using a porous material, particularly a molecular sieve (desiccant) that can strongly adsorb water molecules so that the target gas after the reaction passes through. An impurity medium portion capable of reacting with the impurities may be provided in the impurity separating portion 14 to separate the impurities. The medium may use an exhaust gas purifying device. In addition to the above-mentioned methods, other methods may be adopted, and they may be used alone or in combination.

After separating impurities, the target gas may be delivered to the first supply port 10e of the compressor through the exhaust port 14g of the gas cooling part 14b, and re-introduced into the nuclear reaction vessel 10 a.

Wherein the target gas is continuously reduced with the synthesis of RI-labeled compounds, it is generally recommended to provide the gas replenishing portion 16 responsible for replenishing the target gas. Specific replenishment positions in general, it is recommended to provide a first replenishment position between the gas feed port 10b of the compressor of the gas-filling section 10 and the introduction port 10c of the nuclear reaction vessel 10a, and a second replenishment position between the gas discharge port 13b of the RI-labeled compound synthesis section 13 and the fourth supply port 14c of the gas-cooling section 14 b.

In the first replenishment position, a first gas supply pipe 16a for the target gas is generally provided between the pressure regulating valve 10i and the third pressure gauge 10j, and replenishment of the target gas is controlled by the first gas supply valve 16 b. In the second replenishment position, a fourth pressure valve 16c is generally provided between the exhaust port 13b of the RI label compound synthesizing section 13 and the fourth supply port 14c of the gas cooling section 14b, a second gas supply pipe 16b for the target gas is provided between the fourth pressure valve 16c and the exhaust port 13b of the RI label compound synthesizing section 13, and replenishment of the target gas and renewal (replacement with new target gas) of the target gas which is repeatedly used are controlled by the second gas supply valve 16 e. In particular, since the target gas replenished from the gas replenishing portion 16 through the second gas replenishing pipe 16d is supplied to the nuclear reaction vessel 10a through the gas cooling portion 14b, the target gas from which impurities are separated can be filled in the nuclear reaction vessel 10 a. The first gas supply pipe 16b and the second gas supply pipe 16e are connected to a gas supply port 16f, and the gas supply port 16f draws target gas from a target gas cylinder (not shown).

In the present invention, when the target gas is neon, 18F can be easily produced using inexpensive neon, and RI-labeled compounds for PET examination can be synthesized for tens of people per day¹⁸F-FDG. The invention can recycle and recycle neon as raw material, and can realize remote operation in the whole process, thereby completely preventing operators from being injured by radiation. Further, since the use of expensive heavy oxygen water is not required, PET examination can be made inexpensive in developing countries, and this contributes to cancer detection in countries other than the developing countries.

The present invention will be specifically described below based on practical embodiments, and the present invention is not limited to the following cases.

First, based on fig. 1, we produced a trial of the RI-labeled compound production apparatus 1. As shown in fig. 2, the RI-labeled compound production apparatus 1 includes a gas filling portion 10 of a circulation type compressor that fills neon, a target gas, into a nuclear reaction vessel 10a, a gas sealing portion 11 of a pair of pressure valves, an RI-labeled compound synthesis portion 13 having a storage portion 13d that stores liquid glucose, and an impurity separation portion 14 that separates impurities using liquid nitrogen cooling. The radiation irradiating section 12 is replaced by gamma ray irradiation of an existing facility. The RI-labeled compound synthesizing portion 13 is also provided with a temperature adjusting portion 13j that maintains the temperature of the storage portion 13 d.

As shown in fig. 3, the first pipe 10d of the gas filling part 10 is responsible for transporting the target gas and is connected to the introduction port 10c of the nuclear reaction vessel 10 a; the nuclear reactor 10ade is further provided with a first pressure valve 11a and a second pressure valve 11b at the inlet port 10c and the outlet port 10f, respectively. A first pressure gauge 11c is provided between the exhaust port 10f of the nuclear reaction vessel 10a and the second pressure valve 11 b. The first pipe 10d is provided with a second pressure gauge 10g, a third pressure valve 10h and a third pressure gauge 10 j. The target gas discharged from the impurity separating section 14 is returned to the compression device through the second line 14 a. A third line 11d connected to the second pressure valve 11b is provided with a first pressure gauge 11c and a second supply port 13c of the RI-labeled compound synthesizing section 13, and a fourth pressure gauge 11f is provided therebetween. A glucose supply valve 13h and a storage part 13d are provided¹⁸And a take-out valve 13i for F-FDG. The separation section 14d is fixed inside the gas cooling section 14b filled with liquid nitrogen. A second gas supply pipe 16d is provided between the exhaust port 13b of the storage portion 13d and the fourth pressure valve 16c, and is connected to a gas supply port 16f through a second gas supply valve 16 e. The gas supply port 16f is connected to the first gas supply pipe 16a through a first gas supply valve 16b, and leads to the first line 10 d.

The prototype of this RI-labeled compound production apparatus 1 produced neon as a target gas and sealed in a nuclear reaction vessel, and irradiated tungsten with an electron beam using an electron linear accelerator to obtain gamma rays of bremsstrahlung and irradiated the nuclear reaction vessel to produce¹⁸F, thereby manufacturing¹⁸F-FDG, Synthesis efficiency thereofHigh. The neon irradiated by the radioactive rays can be completely recovered and input into the nuclear reaction container again, and is repeatedly irradiated by the gamma rays to generate¹⁸F, thereby manufacturing¹⁸The synthesis efficiency of the F-FDG process is unchanged. The prototype can be said to completely realize the recycling of target gas, and the manufacturing efficiency of radioactive isotope is high; in addition, the possibility of radiation damage is nearly zero, and inexpensive supply is possible.

As described above, the present invention relates to an apparatus and a method for producing an RI-labeled compound, which are useful for examinations using an RI-labeled compound, such as PET examinations and SPECT examinations; it is useful not only in the medical field but also in the production of RI-labeled compounds used in various fields such as research, industry and food. Further, recycling of target gas can be realized, production efficiency of radioisotopes can be improved, and the possibility of radiation damage can be reduced, which has a great potential as a production apparatus and a production method capable of providing RI-labeled compounds at low cost.

Claims

1. A method for producing an RI-labeled compound, characterized in that: the method comprises the following steps:

a gas filling step of filling target gas into the nuclear reaction vessel; a gas sealing step of sealing the nuclear reaction vessel filled with the target gas; a radiation irradiation step of irradiating the inside of a nuclear reaction vessel in which the target gas is sealed with radiation for a predetermined time to cause nuclear reaction of the target gas; an RI-labeled compound synthesis step of synthesizing an RI-labeled compound by reacting the compound with the target gas containing the radioisotope after the irradiation with the radiation; and an impurity separation step of separating impurities in the target gas after the reaction with the compound and returning the target gas after the separation of the impurities to the nuclear reaction vessel.

2. A method for producing an RI-labeled compound according to claim 1, characterized in that: the method for separating impurities in the target gas after the reaction with the compound may employ one or a combination of more of the following: a method of removing impurities by cooling the target gas to liquefy the impurities contained in the target gas; a method of removing impurities by providing an impurity adsorbing portion capable of adsorbing water and small-molecule impurities and allowing only a target gas to pass therethrough; a method for separating impurities by providing a medium capable of reacting with the impurities.

3. The manufacturing method for manufacturing an RI-labeled compound according to claim 2, characterized in that: further comprising the step of replenishing the target gas during the gas filling step and/or before the impurity separation step.

4. The manufacturing apparatus for manufacturing an RI labeled compound according to any one of the above claims 1 to 3, wherein: the device comprises the following parts: a gas filling portion that fills a target gas into the nuclear reaction vessel; a gas seal portion for sealing the nuclear reaction vessel filled with the aforementioned target gas; a radiation irradiation section for irradiating the target gas with radiation for a predetermined time in a nuclear reaction vessel in which the target gas is sealed, thereby causing a nuclear reaction in the target gas; an RI-labeled compound synthesizing section for synthesizing an RI-labeled compound by reacting the compound with the target gas containing the radioisotope after the irradiation with the radiation; and an impurity separating part for separating impurities from the target gas after the reaction with the compound and returning the target gas after the separation of impurities to the nuclear reaction vessel.

5. The apparatus of claim 4, wherein: the target gas is neon, the radioactive rays are gamma rays, and the RI labeled compound is¹⁸F-FDG。

6. The apparatus of claim 5, wherein: the pressure of the target gas filled in the nuclear reaction vessel is higher than the standard pressure.

7. The apparatus of claim 6, wherein: when the radioactive rays are gamma rays, the radiation irradiating part comprises an electron beam irradiating part of an electron linear accelerator capable of irradiating electron beams with rated energy; a gamma ray emitting part which is arranged beside the nuclear reaction vessel and is provided with a target containing tungsten and can generate gamma rays after being irradiated by electron beams.

8. The apparatus of claim 7, wherein: the impurity separation section includes a cooling section for cooling the target gas after the reaction with the compound to 0 ℃ or lower.