KR100766568B1 - System and method for the production of 18f-fluoride - Google Patents

Abstract

A system and method for producing ¹⁸ F-fluoride that emits ¹⁸ O in gaseous form using a quantum beam. The spun 18O is contained in a chamber containing at least one component to which the resulting ¹⁸ F-fluoride is attached. When at least one chamber component is in the chamber, a solvent is used to dissolve the ¹⁸ F-fluoride produced from the at least one chamber component. This solvent is then treated to yield ¹⁸ F-fluoride.

Description

SYSTEM AND METHOD FOR THE PRODUCTION OF 18F-FLUORIDE

Cross Reference to Related Technologies

This application claims priority based on 35 USC §119 (e) of U.S. Provisional Application 60 / 184,352, filed February 23, 2000, the entirety of which is hereby expressly incorporated by reference.

The present invention relates to a technique for producing ¹⁸ F-fluoride from ¹⁸ O gas.

Many medical procedures for diagnosing the properties of biological cells and the functionality of tissues containing these cells require a radiation source that is introduced into or collected by the cells. Such a radiation source preferably has a very small lifespan that is not long enough to cause radiation damage to the cells or is short enough to extinguish before completing the diagnosis. Such a radiation source is preferably not chemically toxic. ¹⁸ F-fluoride is such a radiation source.

¹⁸ F-fluoride has a lifespan of approximately 109.8 minutes and is not chemically toxic in tracer amounts. Thus, ¹⁸ F-fluoride is widely used in the manufacture of medical and radiopharmaceutical products. ^{The 18} F-fluoride isotope can be used for labeling compounds via the nucleophilic fluorination pathway. In one example ¹⁸ F-fluoride is important for forming radiation tracer compounds for use in positron emission tomography (PET) imaging. Fluoro-deoxyglucose (FDG) is an example of a spinning tracer compound comprising ¹⁸ F-fluoride. In addition to FDG, compounds suitable for labeling with ¹⁸ F-fluorides include fluorine-dioxyglucose, fluoro-thymidine (FLT), fluorine analogues of fatty acids, fluorine analogues of hormones, peptides ) Binders for labeling, DNA, oligo-nuclitide, proteins and amino acids, but are not limited thereto.

Several nuclear reactions induced through radiation of nuclear beams (including quantum, quantum, alpha particles, etc.) produce isotope ¹⁸ F-fluoride. ^The nuclear reaction to form the ¹⁸ F-fluoride is ²⁰ Ne (d, α) ¹⁸ F (symbol indicating that ²⁰ Ne absorbs quantum to produce ¹⁸ F and alpha particles are released), ¹⁶ O (α, pn) ¹⁸ F, ¹⁶ O ( ³ H, n) ¹⁸ F, ¹⁶ O ( ³ H, p) ¹⁸ F and ¹⁸ O (p, n) ¹⁸ F, including but not limited to. Here, ¹⁸ O (p, n) ¹⁸ F has the largest cross section, so the yield of ¹⁸ F is the largest. Several elements and compounds (including neon, water and oxygen) are used to obtain ¹⁸ F-fluoride through nuclear reaction.

Technical and economic considerations are important factors in the selection of an ¹⁸ F-fluoride production system. ^Since the half-life of ¹⁸ F-fluoride is approximately 109.8 minutes, ¹⁸ F-fluoride manufacturers prefer a nuclear reaction with a large cross section (ie, with high efficiency of isotope preparation) to produce large amounts of ¹⁸ F-fluoride quickly. In addition, since the ¹⁸ F- about 109.8 minutes, the half-life of fluoride, ¹⁸ the user's F- ¹⁸ F- fluoride is a fluoride production facility near their other equipment to prevent the loss of a significant classification of the produced during transfer isotope Prefer to have Advances in accelerator design have made it possible to use quantum beam sources with higher energy and current.

Systems that generate quantum beams are not only less complicated than systems that generate other types of beams, but are also simple to operate and manage. Thus, in view of technical and economic considerations, users have preferred a ¹⁸ F-fluoride manufacturing system that uses quantum beams and uses as much power output available in the quantum beams. Users have also become economical in their use and conservation of expensive starting compounds.

However, due to the technical difficulty in implementing the inherent characteristics and F- ¹⁸ fluoride manufacturing system of the ¹⁸ F- fluoride it could reduce the cost of manufacturing a F- ¹⁸ fluoride. Existing methods using neon as starting material inherently suffer from low nuclear reaction yields and complex radiation equipment. The yield from the neon reaction is approximately half of the yield of ¹⁸ O (p, n) ¹⁸ F. In addition, the use of neon as the starting material necessitates a facility for generating more complex quantum beams than a facility for generating quantum beams.

Thus, the use of neon as the starting material has a low ¹⁸ F-fluoride production rate compared to many costs.

Existing methods using ¹⁸ O concentrated water as starting material have the problem of recovering unused ¹⁸ O concentrated water and limiting beam intensity (energy and current) to control water properties. ^{Using 18} O-concentrated water is slower because the production cycle is slower because it requires a relatively long time to collect and dry unused ¹⁸ O-condensed water before the ¹⁸ F-fluoride formed is collectable. there is a problem. Accelerating the manufacturing cycle at the expense of all unused ¹⁸ O concentrated water increases the cost due to unproductive loss of starting material. In addition, the recovery of unused ¹⁸ O concentrated water is problematic due to contaminant by-products resulting from spinning and chemical treatment. This problem allows the user to distill water before reusing it, thus implementing a complex distillation apparatus. This recovery problem complicates the systems and manufacturing procedures used in the preparation of ¹⁸ F-fluorides based on ¹⁸ O enriched water. In addition, this recovery problem results in partly unproductive loss of starting material and lower production rates due to isotope dilution.

Moreover, even if quantum beam currents greater than 100 mA are readily available, water based systems with ¹⁸ O enriched water will evaporate when the quantum beam current increases if the quantum beam current is greater than approximately 50 mA. It is unreliable because it begins to cooperate. Cavitation and evaporation of water interferes with nuclear reactions, thus limiting the range of useful quantum beam currents available for making ¹⁸ F-fluoride from water. See, eg, Heselius, Schlyer, and Wolf, Appl. Radiat. Isot. Vol. 40, no. 8, pp 663-669 (1989). ^The system of implementing a method of using ¹⁸ O-concentrated water to prepare ¹⁸ F-fluoride is complicated and difficult. For example, in the latest publications incorporated herein by reference (see, eg, Helmeke, Harms, and Knapp, Appl. Radiat. Isot. 54, pp 753-759 (2001)), the ability of water to concentrate ¹⁸ O. It is shown that it is necessary to use a complex quantum beam sweeping mechanism because it needs to have a larger target window in order to increase the beam current to 30 ㎂. Despite the complex radiation system and target design, the Helmeke approach apparently allowed for an hour of operation per day.

Therefore, in the case of using water as the starting material, the production rate of ¹⁸ F-fluoride is low despite the large cost.

Thus, there is a need for a better, more efficient and less expensive method of producing ¹⁸ F-fluoride.

The present invention provides a method for producing ¹⁸ F-fluoride by radiating ¹⁸ O in gaseous form using a quantum beam. The spun ¹⁸ O is contained in a chamber containing at least one component to which the produced ¹⁸ F-fluoride is attached. A solvent is used to dissolve ¹⁸ F-fluoride from at least one component when at least one component is in the chamber. The solvent is then treated to give ¹⁸ F-fluoride.

The method according to the invention has the advantage of obtaining ¹⁸ F-fluoride by radiating ¹⁸ O in gaseous form using a quantum beam. In the present invention, the yield according to the invention is high because the nuclear reaction for generating ¹⁸ F-fluoride from ¹⁸ O in gaseous form has a relatively large cross section. The method according to the invention also has the advantage of preserving unused ¹⁸ O and allowing for regeneration and use. The method according to the invention does not appear to be limited to only the quantum beam current currently available. The method according to the invention works well at beam currents greater than 100 mA. Thus, the method according to the invention allows the use of higher quantum beam currents, thus increasing the ¹⁸ F-fluoride production rate. The process according to the invention also has the advantage of generating pure ¹⁸ F-fluoride without generating other non-radioactive fluorine isotopes (eg ¹⁹ F).

Other aspects and advantages of the invention will be apparent from the following detailed description and the accompanying drawings, which are set forth for purposes of illustration only and are not intended to limit the invention.                 

1 is a general block diagram illustrating an example of a system according to the present invention; And

FIG. 2 is a general flow diagram illustrating a method of using the example of FIG. 1 to produce ¹⁸ F-fluoride from ¹⁸ O. FIG.

The present invention provides a method of producing ¹⁸ F-fluoride by radiating ¹⁸ O in gaseous form using a quantum beam. The spun ¹⁸ O is contained in a chamber containing at least one component to which the resulting ¹⁸ F-fluoride is attached. A solvent is used to dissolve ¹⁸ F-fluoride from the at least one component while the at least one component is in the chamber. This solvent is then treated to give ¹⁸ F-fluoride.

1 is a diagram illustrating an example of a system in accordance with the inventive concept. As shown, the ¹⁸ F-fluoride forming system 1 is a hermetically sealed annular tube connecting the target chamber 200 to a vacuum pump 400 and several inlets 601-604 and outlets 701-705. 100. Annular tube 100 has valves 501-513 that separate at least several segments from each other. The pressure gauges 301-303 are preferably connected to the annular tube 100 to allow measuring pressure in several segments of the annular tube 100 at different stages. In one example, stainless steel was used as the material for the annular tube 100. In other examples, other suitable materials are used.

In the example of FIG. 1, the valve is a manual valve (eg, a bellows or other suitable manual valve) as shown for valves 501, 502, 510 and 511, and valves 503, 504, 506, 507, 508, As shown for 509, 512, and 513, it is implemented as an automatic valve (eg, a cylindrical valve or other suitable automatic valve driven by a processor). Other suitable combinations may be selected for manual and automatic valves. For example, all valves can be driven by a processor programmed to automate the generation of ¹⁸ F-fluoride. Alternatively, all valves can be made manually.

The target chamber 200 may include a chamber chamber volume 201, a chamber wall 202 (which includes a chiller or a heater, or both) that blocks the quantum beam, and a chamber volume ( At least one chamber window 203, and at least one chamber component 204, to 201. ¹⁸ O is exposed to the quantum beam while in chamber volume 201. Chamber wall 202 and chamber window 203 maintain ¹⁸ O in chamber volume 201. The chamber window 203 sends a large portion of the incoming quantum beam to the chamber volume 201. The resulting ¹⁸ F-fluoride attaches to the chamber component 204. The chamber component 204 here provides an attachment surface to which the ¹⁸ F-fluoride generated in the chamber 200 is attached. Chamber as the window 203 and Barr (Havar) - that are used (cobalt-nickel alloy), because the elongation strength and Barr (thus maintaining a higher pressure the ¹⁸ O gas in the chamber 200) and the preferred proton This is because of beam transmission (thus transmitting quantum beams with very little loss). However, other suitable materials may be used instead of Havar to form the chamber window. The chamber volume 201 preferably has a flame burning in a conical shape, so that the scattered protons can be efficiently used when proceeding into the chamber volume 201. However, other suitable shapes may be used for the chamber volume 201. In the example used to illustrate the invention, the chamber volume 201 was about 15 ml. This excludes the connecting segment of the annular tube 100. Chamber volume 201 may be designed to have other suitable sizes.

In another non-limiting example, a cooling jacket (a non-limiting example of a chiller) may form part of the chamber wall 202 (not shown in FIG. 1), or a heating tape (not limited to a heater). Yes) may form part of chamber wall 202 (not shown in FIG. 1), or both may form part of chamber wall 202. The temperature of the various parts of the chamber 200 is preferably monitored by, for example, a thermocouple (not shown in FIG. 1). By using a cooling jacket, the chamber can be cooled at various stages to produce ¹⁸ F-fluoride. If a heating tape is used, the chamber can be heated at various stages to produce ¹⁸ F-fluoride. Cooling jackets, heating tapes, or both, may be used to control the temperature of the chamber 200. Instead of using a cooling jacket and heating tape, other cooling and heating devices can be used. Cooling and heating devices may be located inside or outside the chamber wall 202. Temperature monitors allow and increase the tracking and automation of the various stages that produce ¹⁸ F-fluoride.

On one side, the chamber 200 is connected to an annular tube 100 and a pressure transducer 301. The annular tube 100 side has a valve 505 that breaks the continuity of the annular tube 100. On the other side, the chamber 200 is also connected to the annular tube 100. The other side of this annular tube 100 has a valve 506 that breaks the continuity of the annular tube 100. The annular tube 100 has a vacuum pump outlet 701 which is connected to the vacuum pump 400 via a valve 504 behind the valve 505 (pressure transducer between the valve 504 and the vacuum pump 400). 302 is located). An annular tube 100 also has an inlet ¹⁸ O 601 is connected to the ¹⁸ O through the valve 503 after the valve 505. The continuity of annular tube 100 after inlet 601 and outlet 701 is interrupted by valve 512, after which annular tube 100 has a helium inlet 603 that connects to helium gas. . The continuity of the annular tube 100 after the inlet 603 is broken by the valve 510, after which the separator outlet 702 allows connection from the annular tube 100 to the separator 1000. Separator 1000 is connected to a bidirectional valve 513 that connects to waste outlet 703 or product outlet 513. The continuity of the annular tube 100 after the outlet 702 is broken by the valve 509. Following the valve 509, the annular tube 100 has a smoke outlet 705 leading to the valve 508 and a solvent inlet 602 leading the solvent through the valve 507 to the annular tube 100. After solvent inlet 602, annular tube 100 is connected to valve 506.

^{An 18} O inlet 601 is connected to a vessel 800 that stores ¹⁸ O unused (first through valve 503 and then through valve 501). Pressure gauge 303 monitors the pressure in the region between valves 501 and 503. The valve 502 separates the region from the ¹⁸ O vessel used to finish the ¹⁸ O whenever necessary. The vessel 800 may be located in a cryogenic cooler implemented as a liquefied nitrogen vacuum bottle 900 connected to a source of liquefied nitrogen to selectively cool the vessel 800 below the ¹⁸ ° boiling point. Selective cooling can be accomplished, for example, by moving the vacuum bottle up so that the vessel 800 is located in the liquid nitrogen. Instead of a liquefied nitrogen vacuum bottle 900 that selectively cools the vessel 800, in another embodiment, the vessel 800 may be capable of selectively lowering the temperature of the vessel 800 below the boiling point of, for example, ¹⁸ O. It can be accommodated inside.

The following describes a method of implementing the inventive concept with reference to FIG. 2 as an exemplary method using the example of FIG. 1.

Initially valves 501-153 are closed. After the initial or prolonged storage of the first run, and when it is unclear whether the degree of contamination has increased, it is desirable to vent the air in the vessel 800 to reduce many contaminants that may be present. This can be accomplished, for example, by opening the valves 501-503-504 and exposing the vessel 800 to the vacuum pump 400. In step S1000 of FIG. 2, the vessel 800 is filled with ¹⁸ O gas up to a predetermined pressure. This can be accomplished by closing valve 503, opening valves 501, 502, and filling vessel 800 with ¹⁸ O gas while monitoring pressure with pressure gauge 303.

In step S1010, air is drawn out of the chamber volume 201 (pumping out). This is achieved, for example, by opening the valves 504, 505, exposing the chamber volume 201, and connecting the vacuum pump 400 to the chamber volume 400. The vacuum pump may be implemented by, for example, a mechanical pump, a diffusion pump or both. Pressure gauge 302 is used to keep track of the vacuum level of chamber volume 201. The valves 503-506-512 are closed to efficiently evacuate the chamber volume 201 during step S1010. When the desired vacuum level in chamber volume 201 is achieved, valve 504 is closed, so vacuum pump 400 is separated from chamber volume 201. The predetermined vacuum level in chamber volume 201 is preferably sufficiently high such that the amount of contaminants is low compared to the amount of ¹⁸ F-fluoride formed each time the contaminant runs. Step S1010 can be increased by heating the chamber 200 to accelerate pumping.

In step S1020 the chamber volume 201 is filled with ¹⁸ O gas to a predetermined level. This can be accomplished, for example, by opening the valves 501-503-505 and allowing ¹⁸ O gas to enter the chamber volume 201 from the vessel 800. The pressure gauge 301, the pressure gauge 303, or both can be used to keep track of the pressure in the chamber volume 201 and the amount of ¹⁸ O gas.

In step S1030, the ¹⁸ O gas in the chamber volume 201 is emitted with a quantum beam. This can be accomplished, for example, by closing the valve 505 and directing the quantum beam onto the chamber window 203. The chamber window 203 may be made of thin metal flakes that transmit quantum beams while receiving ¹⁸ O gas and ¹⁸ F-fluoride generated. ^{When the 18} O gas is being emitted by the quantum beam, the ¹⁸ O nucleus causes a nuclear reaction and is converted into ¹⁸ F-fluoride. The nuclear reaction that occurs is as follows.

The spin time can be calculated based on well-known formulas relating to the preferred amount of ¹⁸ F-fluoride, the initial amount of ¹⁸ O gas present, the quantum beam current, the quantum beam energy, the reaction cross section and the half-life of the ¹⁸ F-fluoride. Table 1 shows the predicted yields for 100 quantum beam currents and different emission times at different quantum energies. TTY is an abbreviation for yield when the target is thick enough to fully absorb the quantum beam.

TTY is an abbreviation for thick target yield where the ¹⁸ O gas emitted is thick enough, ie sufficient pressure, for all transmitted quantum beams to be absorbed by ¹⁸ O. The unit of yield is Curie. TTY in Sat is about 12 hours yield for ¹⁸ O gas if the spinning time is long enough for the yield to saturate.

It is preferred that the ¹⁸ O gas be at a high pressure. The higher the pressure becomes, the length of the chamber volume 201 is shorter ¹⁸ O gas is displayed in a thick target for the proton beam. Table 2 shows the stationary power of oxygen in gm / cm 2 for various incident quantum energies. The length of ¹⁸ O gas (gas at certain temperature and pressure) required to fully absorb the quantum beam at a particular energy is provided by dividing the stationary power of oxygen by the density of ¹⁸ O gas (density at specific temperature and pressure). Using this equation, an ¹⁸ O gas of about 155 cm in length at STP (300 K temperature and 1 atm pressure) is needed to fully absorb a quantum beam with an energy of 12.5 MeV. Increasing the pressure to 20 atm requires a length of about 7.75 cm at 300 K.

In conclusion, in one embodiment, the chamber 200 (along with portions thereof) is designed to withstand high pressure because the chamber 200 and the gas are required to be heated when heated due to radiation by the quantum beam. . ^In one embodiment according to the invention for producing ¹⁸ F-fluoride from ¹⁸ O gas, the inventors have used a Havar with a thickness of 40 microns to produce a 13 MeV quantum beam (12.5 Mev is the chamber volume) at a beam current of 20 mA. And 0.5 Mev was absorbed by the Havar chamber window) and successfully contained ¹⁸ O at a filling pressure of ²⁰ atm. This embodiment is the ¹⁸ O gas, and thereto ¹⁸ O gas having a much higher temperature (greater than 100 ℃) and pressure than the charge temperature and pressure prior to radiation during radiation along with proton beam was successfully accepted. In another embodiment, a cooling jacket (line) was used to remove heat from the chamber volume during spinning. The preferred implementation implements the inventive concept at high pressure to have a relatively short chamber length and simplifies the need for the intensity of the incident quantum beam. In other embodiments, other suitable designs may be used to receive ¹⁸ O gas at the desired pressure.

^{The 18} F-fluoride is attached to the chamber component 204 when formed. The material selected for the at least one chamber component 204 preferably adheres well to the ¹⁸ F-fluoride. The material selected as chamber component 204 preferably dissolves readily when the attached ¹⁸ F-fluoride is exposed to a suitable solvent. Such materials include, but are not limited to, stainless steel, glassy carbon, titanium, silver, gold plated metals (such as nickel), niobium, Havar, aluminum, and nickel plated aluminum. Periodic pre-fill treatment of the chamber component 204 may be used to improve the adhesion (and / or subsequent dissolution of ¹⁸ F-fluoride, see step S1050 below).

In step S1040, an unused portion of ¹⁸ 0 is removed from the chamber volume 201. This is, for example, be achieved a valve (501-503-505) as yeoleum while cooling the vessel 800 below the boiling point of the ¹⁸ O. In this case the unused portion of ¹⁸ O is attracted to the vessel 800 and can thus be used in the next run. This step makes it possible to efficiently use the starting material ^18O . It should be noted that cooling the vessel 800 below the boiling point of ¹⁸ O may be performed when the chamber volume 201 is spinning during step S1030. Such an implementation according to the inventive concept reduces travel time when different steps are performed in parallel with different segments of the annular tube 100 which are separated from each other by, for example, several valves. The pressure of the ¹⁸ O gas can be monitored by the pressure gauge 303, the pressure gauge 301, or both.

In step S1050, the formed ¹⁸ F-fluoride attached to the chamber component 204 is preferably dissolved using a solvent without removing the chamber component 204 from the chamber 200. This can be accomplished, for example, by opening the valves 506-507 with the valve 505 closed to allow solvent to be introduced into the chamber volume 201. The attached ¹⁸ F-fluoride is preferably dissolved by and into the solvent introduced. Step S1050 may be augmented by heating the chamber 200 to accelerate dissolution of the resulting ¹⁸ F-fluoride. This procedure causes the solvent to fall into the vacuum present in the chamber volume 201, thus helping to introduce the solvent or to physically clean the chamber component 204. Alternatively, the solvent may also be introduced because of its flow pressure.

The material used as the solvent should readily remove (physically and / or chemically) the ¹⁸ F-fluoride attached to the chamber component 204 and also be capable of separating the dissolved ¹⁸ F-fluoride uncontaminated. It is preferable. The solvent also preferably does not corrode system components that the solvent contacts. Examples of such solvents include, but are not limited to, water, acids and alcohols in liquid and vapor forms. ¹⁹ fluorine is not suitable as a solvent. This mixture has ¹⁸ F- ¹⁹ F molecules that are not easily separated, thus reducing the yield of the ultimate ¹⁸ F-fluoride based compound produced.

Table 3 shows the various percentages of the resulting ¹⁸ F-fluoride extracted with water at various temperatures. It can be seen from Table 3 that the chamber component consisting of stainless steel yields 93.2% of the ¹⁸ F-fluoride formed by washing twice with water at 80 ° C. On the other hand, glassy carbon yields 98.3% of the ¹⁸ F-fluoride formed by washing once with 80 ° C of water. The washing time was about 10 seconds. The use of higher temperature water is expected to improve the yield from cleaning. The steam is not better than water in dissolving the ¹⁸ F-fluoride formed but is expected to perform at least as much as water. Other solvents may be used instead of water, with the goal of rapidly dissolving the ¹⁸ F-fluoride formed without dilution of the ultimate compound based on fluorine.

In step S1060, the ¹⁸ F-fluoride formed is separated from the solvent. This can be accomplished, for example, by closing the valve 507 and opening the valves 512-505-506-509 and directing the bidirectional valve 513 to the waste outlet 703. This forces helium out of the chamber volume 201 towards the separator 1000 with the ¹⁸ F-fluoride dissolved therein. Separator 1000 separates the ¹⁸ F-fluoride formed from the solvent, maintains the ¹⁸ F-fluoride formed, and discharges the solvent through waste outlet 703.

Separator 1000 can be implemented using a number of methods. One implementation for separator 1000 is to use an ion exchange column that attracts anions (the ¹⁸ F-fluorides formed are anions) and separates the ¹⁸ F-fluorides from the solvent. For example, Dowex X-10, 200-400 mesh commercial resin or Toray TIN-200 commercial resin can be used as the separator. Another embodiment is to use a separator having particularly strong affinity with the formed ¹⁸ F-fluoride, for example QMA Sep-Pak. This implementation of separator 1000 preferentially separates and maintains ¹⁸ F-fluoride, but does not retain radioactive metal byproducts (cations) from the solvent, and thus can maintain high purity of the radioactive ¹⁸ F-fluoride formed. Another implementation for separator 1000 is to use a filter that holds the ¹⁸ F-fluoride formed.

In step S1070, the separated ¹⁸ F-fluoride is processed in separator 1000. This can be accomplished, for example, by closing the valves 509-512, opening the valves 510-511, and directing the valve 513 to the product outlet 704. Helium then directs the eluant to separator 1000. Eluent treats the ¹⁸ F-fluoride separated from separator 1000 and delivers it to product outlet 704. The eluent used should have an affinity for the separated ¹⁸ F-fluoride that is stronger than the affinity of separator 1000. Various chemicals used as eluents include, but are not limited to, various kinds of bicarbonates. Non-limiting examples of bicarbonates that can be used as eluents are sodium-bicarbonate, potassium-bicarbonate and tetrabutyl-ammonium-bicarbonate. Other anionic eluents can be used in addition to or instead of bicarbonate. The user can then obtain a treated ¹⁸ F-fluoride that has passed through the product outlet 704 and use it, for example, for the nucleophilic reaction.

In step S1080, the chamber volume 201 is dried in preparation for another run to form ¹⁸ F-fluoride. This may be accomplished, for example, by closing valve 511 and closing valves 512-505-506-508. Helium then flows through the chamber volume 201 towards the smoke outlet 705 and from the smoke outlet 705. Pressure gauge 301 may be used to monitor the drying of chamber volume 201. Alternatively, a moisture monitor coupled to the pressure gauge 301 may be used to track the drying of the chamber volume 201. Step S1080 may be augmented by heating the chamber 200 to accelerate drying.

Note that step S1070 and step S1080 can overlap in time. This may be achieved, for example, by opening the valves 512-505-506 with the valves 511-510 open and the valves 509 closed. This allows helium to dry the chamber volume 201 without pushing the moisture toward the separator 702 or the eluent toward the smoke outlet 705 while the eluent passes through the separator 1000 and the product outlet 704. Do it. In addition, helium is described as a gas used to guide solvents and eluents and to dry the chamber volume 201, but the concept of the present invention is to form a ¹⁸ F-fluoride, solvent, eluent or system (pressure gauge, valve). Or any other gas that does not react with the material forming the chamber). For example, nitrogen or argon may be used instead of helium.

After drying chamber volume 201 from the remaining solvent, the system prepares for another run to form a new batch of ¹⁸ F-fluoride. The amount of ¹⁸ O in the vessel 800 can be monitored to determine if finishing is required. The whole process is repeated again starting with step S1010.

The demonstration according to the inventive concept consistently yielded at least about 70% of the ¹⁸ F-fluoride theoretically obtainable from the ¹⁸ O gas. Set the chamber volume to about 15 ml, charge ¹⁸ O gas to a pressure of about 20 atm, quantum beam to 13 MeV with a 20 mA beam current, neutralize 100 ml volume of solvent, and 2x2 ml QMA separator It was dissolved by dissolving in a bicarbonate solvent of. Since the hydrogen ions ¹⁸ O in gas form is present in the ¹⁸ O enriched water has a 14-18% better yield than the ¹⁸ O enriched water to reduce the exposure of the ¹⁸ O for the proton beam the result is of particular importance Do. This yield difference increases as quantum energy decreases. The yield differences at 15, 30, 50 and 100 MeV are 16%, 15.2%, 14.75% and 14.3%, respectively. As a result, the concept of the present invention produces a yield of ¹⁸ F-fluoride that is significantly greater overall than can be produced by a system based on ¹⁸ O concentrated water. For example, running a simple (non-sweeping beam) system that implements the concept of the invention at 100 quantum beam current and 15 MeV of energy will drive a Helméke that can run at up to 30 kHz in appearance. Yields approximately 53% greater overall yield than a complex (swept beam and larger target window) system.

The concept of the present invention can be implemented as a variant of using individual chemical inert gas inlets instead of one inlet to perform several steps simultaneously. The concept of the present invention can also be implemented using a valve to separate the eluent inlet from the annular tube 100. The annular tube 100 may be formed in a circular and other shape bent for the size of the system, but is not limited thereto. The cooling and / or heating device can be used to control the temperature of the material delivered by the annular tube 100 by, for example, surrounding a portion of the annular tube 100 with a cooling and / or heating jacket. The temperature of the annular tube 100 can be monitored by a thermocouple, for example, to better control the temperature of the transferred material. Parallel instead of one annular tube to increase the surface area and to heat and / or cool better than the different materials (gas / eluent / solvent) transferred by the cooling and / or heating device surrounding the annular tube. Annular tubes may be used. The chamber and its other parts can be formed of a variety of different suitable designs and materials. This is done for example to increase the incident quantum beam current.

While the invention has been described in considerable detail with reference to specific examples, it is evident that various modifications and applications of the invention can be made without departing from the scope and spirit of the invention. All modifications and variations apparent to those skilled in the art are intended to be included within the scope of the claims set forth herein.

Claims (20)

Placing a molecule of ¹⁸ O gas into a chamber comprising at least one attachment surface to which the ¹⁸ F-fluoride attaches; At least by a proton beam having a beam current of 100㎂ attaching the attachment surface emitting the ¹⁸ O gas by converting a portion of ¹⁸ O by ¹⁸ F- fluoride, and the F- ¹⁸ fluoride is at least one in the chamber ; And And exposing the at least one mounting surface in a solvent within the chamber, the at least one attaching preparing a F- ¹⁸ fluoride from ¹⁸ O to the ¹⁸ F- fluoride attached to a surface comprising the step of dissolving Way. The method of claim 1, ^{18. The} method of claim ¹⁸ , wherein said solvent is water. The method of claim 2, Wherein said solvent is water at a temperature equal to or greater than 80 ° C. ¹⁸ . The method of claim 2, ^{18. The process} of claim ¹⁸ , wherein said solvent is a vapor. The method of claim 1, To through the separator to maintain the dissolved ¹⁸ F- F- ¹⁸ fluoride producing a fluoride, characterized in that further including the step of removing the solvent from the chamber. The method of claim 1, Method for producing a F- ¹⁸ fluoride characterized in that it comprises the further step of removing non-converted portion of the ¹⁸ O gas from the chamber. The method of claim 1, ^18, how to use a separator having high affinity with F- fluoride producing a F- ¹⁸ fluoride, characterized in that further including the step of separating the solubilized F- ¹⁸ fluoride from the solvent. The method of claim 1, How to use the ion exchange column to attract negative ions produced an ¹⁸ F- fluoride, characterized in that further including the step of separating the solubilized F- ¹⁸ fluoride from the solvent. The method of claim 8, ^{18. The} method of claim ¹⁸ , further comprising treating the separated ¹⁸ F-fluoride. The method of claim 8, Method for producing a F- ¹⁸ fluoride, characterized in that further including the step of drying the chamber. ^A container suitable for holding ¹⁸ O gas; At least one chamber wall that is operably connected to the vessel and optionally filled with a gas comprising ¹⁸ O ₂ gas, the chamber having at least one chamber wall therethrough and containing at least one attachment surface to which the ¹⁸ F-fluoride attaches chamber; A solvent inlet for supplying a solvent operatively connected to the chamber and capable of removing the ¹⁸ F-fluoride attached to the at least one attachment surface; And System from ¹⁸ O comprising a solvent outlet for removing the solvent from the chamber produced a F- ¹⁸ fluoride. The method of claim 11, The solvent is a system for producing ¹⁸ F-fluoride, characterized in that the water. The method of claim 12, Wherein said solvent is water at a temperature equal to or greater than 80 ° C. ¹⁸ . The method of claim 12, The solvent is a system for producing ¹⁸ F-fluoride, characterized in that the water vapor. The method of claim 11, The ¹⁸ O contained in the gas container by adding a cold trap connected drivingly, and the cooling trap system for producing a F- ¹⁸ fluoride, characterized in that for liquefying the ¹⁸ O gas. The method of claim 11, The separator further comprises a separator connected to the chamber to drive small, the system for producing a F- ¹⁸ fluoride, characterized in that to allow removal of the solvent from the system while maintaining the dissolution of F- ¹⁸ fluoride. The method of claim 16, The separator system for preparing ¹⁸ F- fluoride, characterized in that it has a high affinity and F- ¹⁸ fluoride. The method of claim 16, The separator system for preparing ¹⁸ F- fluoride characterized in that the ion exchange column to attract anions. The method of claim 16, System for connecting the separator with being drivingly, producing a F- ¹⁸ fluoride characterized in that it comprises from the separator to the inlet for adding eluent to selectively allow the processing of the maintenance ¹⁸ F- fluoride. The method of claim 18, System that is attached to the chamber and drivingly, producing a F- ¹⁸ fluoride, characterized in that further comprising a chemically inert gas inlet to selectively allow the drying of the chamber.

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