Patent Publication Number: US-2005129162-A1

Title: System and method for the production of 18F-Fluoride

Description:
CROSS REFERENCE TO RELATED APPLICATION  
      This is a continuation application of U.S. Application No. 09/790,572, filed Feb. 23, 2001, which claims priority under 35 U.S.C. §119 (e) of U.S. Provisional Application No. 60/184,352, filed Feb. 23rd, 2000, the entire contents of which are specifically incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION  
      The present invention relates to a technique for producing  18 F-Fluoride from  18 O gas.  
     BACKGROUND OF THE INVENTION  
      Many medical procedures diagnosing the nature of biological tissues, and the functioning of organs including these tissues, require radiation sources that are introduced into, or ingested by, the tissue. Such radiation sources preferably have a life-time of few hours--neither long enough for the radiation to damage the tissue nor short enough for radiation intensity to decay before completing the diagnosis. Such radiation sources are preferably not chemically poisonous.  18 F-Fluoride is such a radiation source.  
       18 F-Fluoride has a lifetime of about 109.8 minutes and chemically poisonous in tracer quantities. It has, therefore, many uses in forming medical and radio-pharmaceutical products. The  18 F-Fluoride isotope can be used in labeling compounds via the nucleophilic fluorination route. One important use is the forming of radiation tracer compounds for use in medical Positron Emission Tomography (PET) imaging. Fluorodeoxyglucose (FDG) is an example of a radiation tracer compound incorporating  18 F-Fluoride. In addition to FDG, compounds suitable for labeling with  18 F-Fluoride include, but are not limited to, Fluorodeoxyglucose (FDG), Fluoro-thymidine (FLT), fluoro analogs of fatty acids, fluoro analogs of hormones, linking agents for labeling peptides, DNA, oligonuclitides, proteins, and amino acids.  
      Several nuclear reactions, induced through irradiation of nuclear beams (including protons, deuterons, alpha particles, ...etc), produce the isotope  18 F-Fluoride.  18 F-Fluoride forming nuclear reactions include, but are not limited to,  20 Ne(d,a) 18 F (a notation representing a  20 Ne absorbing a deuteron resulting in  18 F and an emitted alpha particle),  16 0(a,pn) 18 F,  16 O ( 3 H,n) 18 F,  16 O ( 3 H,p) 18 F, and  18 O(p,n) 18 F; with the greatest yield of  18 F production being obtained by the  18 O(p,n) 18 F because it has the largest cross-section. Several elements and compounds (including Neon, water, and Oxygen) are used as the initial material in obtaining  18 F-Fluoride through nuclear reactions.  
      Technical and economic considerations are critical factors in choosing an  18 F-Fluoride producing system. Because the half-life of  18 F-Fluoride is about 109.8 minutes,  18 F-Fluoride producers prefer nuclear reactions that have a high cross-section (i.e., having high efficiency of isotope production) to quickly produce large quantities of  18 F-Fluoride. Because the half-life of  18 F-Fluoride is about 109.8 minutes, moreover, users of  18 F-Fluoride prefer to have an  18 F-Fluoride producing facility near their facilities so as to avoid losing a significant fraction of the produced isotope during transportation. Progress in accelerator design has made available sources of proton beams having higher energy and currents.  
      Systems that produce proton beams are less complex, as well as simpler to operate and maintain, than systems that produce other types of beams. Technical and economic considerations, therefore, drive users to prefer  18 F-Fluoride producing systems that use proton beams and that use as much of the power output available in the proton beams. Economic considerations also drive users to efficiently use and conserve the expensive startup compounds.  
      However, inherent characteristics of  18 F-Fluoride and the technical difficulties in implementing  18 F-Fluoride production systems have hindered reducing the cost of preparing  18 F-Fluoride. Existing approaches that use  
      Neon as the startup material suffer from problems of inherent low nuclear reaction yield and complexity of the irradiation facility. The yield from Neon reactions is about half the yield from  18 O(p,n) 18 F. Moreover, using Neon as the startup material requires facilities that produce deuteron beams, which are more complex than facilities that produce proton beam.  
      Using Neon as the start-up material, therefore, has resulted in low  18 F-Fluoride production yield at a high cost.  
      Existing approaches that use  18 O-enriched water as the startup material suffer from problems of recovery of the unused  18 O-enriched water and of the limited beam intensity (energy and current) handling capability of water. Using  18 O-enriched water suffers from slower production cycle times as it is necessary to spend relatively long time to collect and dry-up the unused  18 O-enriched water before the formed  18 F-Fluoride can be collected. Speeding production cycle at the expense of recovering all of the unused 18 O-enriched water will increase the cost because of the unproductive loss of the start-up material. Recovering the unused  18 O-enriched water is problematic, moreover, because of contaminating by-products generated as a result of the irradiation and chemical processing. This problem has led users to distill the water before reuse and, thus, implement complex distilling devices. These recovery problems complicate the system, and the production procedures, used in  18 O-enriched water based  18 F-Fluoride generation; the recovery problems also lower the product yield due in part to non-productive startup material loss and isotopic dilution.  
      Moreover, although proton beam currents of over 100 microamperes are presently available,  18 O-enriched water based systems are not reliable when the proton beam current is greater than about 50 microamperes because water begins to vaporize and cavitate as the proton beam current is increased. The cavitation and vaporization of water interferes with the nuclear reaction, thus limiting the range of useful proton beam currents available to produce  18 F-Fluoride from water. See, e.g., Heselius, Schlyer, and Wolf, Appl. Radiat. Isot. Vol. 40, No. 8, pp 663-669 (1989), incorporated herein by reference. Systems implementing approaches using  18 O-enriched water to produce  18 F-Fluoride are complex and difficult. For example, very recent publications (see, e.g., Helmeke, Harms, and Knapp, Appl. Radiat. Isot. 54, pp 753-759 (2001), incorporated herein by reference, hereinafter “Helmeke”) show that it is necessary to use complicated proton beam sweeping mechanism, accompanied by the need to have bigger target windows, to increase the beam current handling capability a of  18 O-enriched water system to 30 microamperes. In spite of the complicated irradiation system and target designs, the Helmeke approach has apparently allowed operation for only 1 hour a day.  
      Using water as the startup material, therefore, has also resulted in low  18 F-Fluoride production yield at high cost.  
      Accordingly, a better, more efficient, and less costly method of producing  18 F-Fluoride is needed.  
     SUMMARY OF THE INVENTION  
      The invention presents an approach that produces  18 F-Fluoride by using a proton beam to irradiate  18 Oxygen in gaseous form. The irradiated  18 Oxygen is contained in a chamber that includes at least one component to which the produced  18 F-Fluoride adheres. A solvent dissolves the produced  18 F-Fluoride off of the at least one component while it is in the chamber. The solvent is then processed to obtain the  18 F-Fluoride.  
      The inventive approach has an advantage of obtaining  18 F-Fluoride by using a proton beam to irradiate  18 Oxygen in gaseous form. The yield from the inventive approach is high because the nuclear reaction producing  18 F-Fluoride from  18 Oxygen in gaseous form has a relatively high cross section. The inventive approach also has an advantage of allowing the conservation of the unused  18 Oxygen and its recycled use. The inventive approach appears not to be limited by the presently available proton beam currents; the inventive approach working at beam currents well over 100 microamperes. The inventive approach, therefore, permits using higher proton beam currents and, thus, further increases the  18 F-Fluoride production yield. The inventive approach has a further advantage of producing pure  18 F-Fluoride, without the other non-radioactive Fluorine isotopes (e.g., 19F). 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      Other aspects and advantages of the present invention will become apparent upon reading the detailed description and accompanying drawings given hereinbelow, which are given by way of illustration only, and which are thus not limitative of the present invention, wherein:  
       FIG. 1  is a general block diagram illustrating an exemplary embodiment of a system according to the present invention; and  
       FIG. 2  is a general flow chart illustrating a method of using the embodiment of  FIG. 1  to produce  18 F-Fluoride from  18 Oxygen gas. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
      The invention presents an approach that produces  18 F-Fluoride by using a proton beam to irradiate  18 Oxygen in gaseous form. The irradiated  18 Oxygen is contained in a chamber that includes at least one component to which the produced  18 F-Fluoride adheres. A solvent dissolves the produced  18 F-Fluoride off of the at least one component while the at least one component is in the chamber. The solvent is then processed to obtain the  18 F-Fluoride.  
       FIG. 1  is a diagram illustrating an exemplary embodiment of a system according to the inventive concept. As shown, the  18 F-Fluoride forming system  1  includes a leak-tight looping tube  100  connecting a target chamber  200  to a vacuum pump  400  and to various inlets ( 601 - 604 ) and outlets ( 701 - 705 ). The looping tube  100  has at least valves ( 501 - 513 ) that separate various segments from each other. Preferably pressure gauges ( 301 - 303 ) are connected to the looping tube  100  to permit measuring the pressure within various segments of the looping tube  100  at different stages. In one implementation, stainless steel was used as the material for the looping tube  100 . Alternative implementations use other suitable material.  
      In the embodiment of  FIG. 1 , the valves are implemented as manual valves (e.g., bellows or other suitable manual valves), as shown for valves  501 ,  502 ,  510 , and  511 , and automated valves (e.g., processor driven solenoid valves, or other suitable automated valves), as shown for valves  503 ,  504 ,  506 ,  507 ,  508 ,  509 ,  512 , and  513 . Other suitable combination can be chosen for the manual and automated valves. For example, all of the valves can be driven by processor(s) programmed to automate the production of  18 F-Fluoride. Alternatively all of the valves can be manual.  
      The target chamber  200  includes an irradiation chamber volume  201 , chamber walls  202  (that can include cooling device(s), or heating device(s) or both) that preferably are proton beam blocking, at least one chamber window  203  that transmits the proton beam into the chamber volume  201 , and at least one chamber component  204 . The  18 Oxygen is exposed to the proton beam while being in the chamber volume  201 . The chamber walls  202  and chamber window  203  retain the  18 Oxygen in the chamber volume  201 . The chamber window  203  transmits a large portion of the incident proton beams into the chamber volume  201 . The produced  18 F-Fluoride adheres to the chamber component  204 . Preferably Havar (Cobalt-Nickel alloy) is used as the chamber window  203  because of its tensile strength (thus holding the  180  gas at high pressures within the chamber  200 ) and good proton beam transmission (thus transmitting the proton beam without significant loss). However, other suitable material, instead of Havar, can be used to form the chamber window. Preferably, the chamber volume  201  conically flares out and, thus, permits the efficient use of the scattered protons as they proceed into the chamber volume  201 . However, other suitable shapes can be used for the chamber volume  201 . The chamber volume  201  in exemplary embodiments used in runs demonstrating the inventive was about 15 milliliters—this excludes the connecting segments of the looping tube  100 . The chamber volume  201  can be designed to have other suitable sizes.  
      In different non-limiting implementations, a cooling jacket (as a nonlimiting example of cooling device) can form part of the chamber wall  202  (not shown in  FIG. 1 ), heating tapes (as a non-limiting example of heating device) can form part of the chamber wall  202  (not shown in  FIG. 1 ), or both. The temperature of the various parts of the chamber  200  can preferably be monitored by, for example, thermocouple(s) (not shown in  FIG. 1 ). Using a cooling jacket allows the cooling of the chamber at various stages of producing  18 F-Fluoride. Using heating tapes allows the heating of the chamber at the various stages of producing  18 F-Fluoride. The cooling jacket, the heating tapes, or both, can be used to control the temperature of the chamber  200 . Instead of a cooling jacket and heating tapes, other cooling and heating devices can be used. The cooling and heating devices can be located inside or outside the chamber wall  202 . Using temperature measuring device(s) permits and augments the tracking and automation of the various stages of the  18 F-Fluoride production.  
      On one side, the chamber  200  is connected to the looping tube  100  and a pressure transducer  301 . This side of the looping tube has a valve  505  interrupting the continuation of the looping tube  100 . On the other side, the chamber  200  is also connected to the looping tube  100 . This other side of the looping tube has a valve  506  interrupting the continuation of the looping tube  100 . After valve  505 , the looping tube  100  has a vacuum pump outlet  701  allowing an access to vacuum pump  400  through valve  504  (with a pressure transducer  302  placed between the valve  504  and the vacuum pump  400 ). After valve  505 , the looping tube  100  also has an  18 Oxygen inlet  601  allowing access to  18 Oxygen through valve  503 . The continuation of the looping tube  100 , after inlet  601  and outlet  701 , is interrupted by valve  512 , after which the looping tube has a Helium inlet  603  allowing access to Helium gas. The continuation of looping tube  100  after inlet  603  is interrupted by valve  511 , after which the looping tube has an Eluent inlet  604 . After the Eluent inlet  604 , the continuation of the looping tube  100  is interrupted by valve  510 , after which separator outlet  702  allows access from the looping tube  100  to a separator  1000 . Separator  1000  leads to a bi-directional valve  513 , which allows access either to waste outlet  703  or to product outlet  704 . After outlet  702 , the continuation of the looping tube  100  is interrupted by valve  509 . Following valve  509 , the looping tube  100  has both a vent outlet  705  leading to valve  508  and a solvent inlet  602  allowing a solvent into looping tube  100  through valve  507 . After solvent inlet  602 , the looping tube  100  connects to the valve  506 .  
      The  18 Oxygen inlet  601  connects (first through valve valves  503  and then through valve  501 ) to a container  800  for storing unused  18 Oxygen. A pressure gauge  303  monitors the pressure at a region between valves  501  and  503 . A valve  502  separates this region from a container of  18 Oxygen to be used to top-off the  18 Oxygen in the system whenever it is deemed necessary. Container  800  can be placed in a cryogenic cooler implemented as a liquid Nitrogen dewar  900  connected to a supply of liquid Nitrogen to selectively cool the container  800  to below the boiling point of  18 Oxygen. The selective cooling can be achieved, for example, by moving the dewar up so as to have the container  800  be in the liquid Nitrogen. Instead of the liquid Nitrogen dewar  900  selectively cooling the container  800 , in other implementations the container  800  can be enclosed in a refrigerator that can selectively lower the temperature of container  800  to below the boiling point of  81 Oxygen, for example.  
      A method of implementing the inventive concept is described hereinafter, by reference to  FIG. 2 , as an exemplary preferred method for using the embodiment of  FIG. 1 .  
      At the very beginning, valves  501 - 513  are closed. At the beginning of a very first run or after long-term storage and when it is unclear whether contaminant level has increased, it is desirable to pump out container  800  to reduce the number of contaminants that might exist otherwise. This can be achieved, for example, by opening valves  501 - 503 - 504  and exposing the container  800  to the vacuum pump  400 . In step S 1000  of  FIG. 2 , the container  800  is filled with  18   0 xygen gas to a desired pressure. This can be achieved by closing valve  503  and opening valves  501  and  502  and filling the container  800  with  18   0 xygen gas, for example, while the pressure is monitored by pressure gauge  303 .  
      In step S 1010 , the chamber volume  201  is evacuated. This can be accomplished, for example, by opening valves  504  and  505  and exposing the chamber volume  201  and the connecting looping tube  100  to the vacuum pump  400 . The vacuum pump can be implemented, for example, as a mechanical pump, diffusion pump, or both. The pressure gauge  302  can be used to keep track of the vacuum level in the chamber volume  201 . During step S 1010 , valves  503 - 506 - 512  can be closed to efficiently pump on chamber volume  201 . When the desired level of vacuum in chamber  201  is achieved, valve  504  can be closed thus isolating the vacuum pump  400  from the chamber volume  201 . The desired level of vacuum in chamber volume  201  is preferably high enough so that the amount of contaminants is low compared to the amount of  18 F-Fluoride formed per run. Step S 1010  can be augmented by heating chamber  200  so as to speed up its pumping.  
      In step S 1020 , the chamber volume  201  is filled with  18   0 xygen gas to a desired pressure. This can be accomplished, for example, by opening valves  501 - 503 - 505  and allowing the  18 Oxygen gas to go from the container  800  to the chamber volume  201 . Pressure gauges  301  or  303 , or both, can be used to keep track of the pressure and, thus, the amount of  18 Oxygen gas in chamber volume  201 .  
      In step S 1030 , the  18 Oxygen gas in chamber volume  201  is irradiated with a proton beam. This can be accomplished, for example, by closing valve  505  and directing the proton beam onto the chamber window  203 . The chamber window  203  can be made of a thin foil material that transmits the proton beam while containing the  18 Oxygen gas and the formed  18 F-Fluoride. As the  18 Oxygen gas is being irradiated by the proton beam, some of the  18 Oxygen nuclei undergo a nuclear reaction and are converted into  18 FFluoride. The nuclear reaction that occurs is: 
 
 18 Oxygen+p→ 18 F+n. 
 
      The irradiation time can be calculated based on well-known equations relating the desired amount of  18 F-Fluoride, the initial amount of  18 Oxygen gas present, the proton beam current, the proton beam energy, the reaction cross-section, and the half-life of  18 F-Fluoride. TABLE 1 shows the predicted yields for a proton beam current of 100 microamperes at different proton energies and for different irradiation times. TTY is an abbreviation for the yield when the target is thick enough to completely absorb the proton beam.  
                                   TABLE 1                                           TTY with   TTY with                   2-Hour   4-Hour               TTY at Sat   Irradiation   Irradiation           Ep (MeV)   (Ci)   (Ci)   (Ci)                                                            12   21   10.5   15.8           15   25   12.5   18.8           20   30   15   22.5           30   46   23   34.5                      
 
      TTY is an abbreviation for thick target yield, wherein the  18 Oxygen gas being irradiated is thick enough-i.e., is at enough pressure—so that the entire  5  transmitted proton beam is absorbed by the  18 Oxygen. The yields are in curie. TTY at sat is the yield when the irradiation time is long enough for the yield to saturate-about 12 Hours for  18 Oxygen gas.  
      Preferably the  18 Oxygen gas is at high pressures: The higher the pressure the shorter the necessary length for the chamber volume  201  to have the  18 Oxygen gas present a thick target to the proton beam. TABLE 2 shows the stopping power (in units of gm/cm 2 ) of Oxygen for various incident proton energies. The length of  18 Oxygen gas (the gas being at a specific temperature and pressure) that is necessary to completely absorb a proton beam at a specific energy is given by the stopping power of Oxygen divided by the density of  18 Oxygen gas (the density being at the specific temperature and pressure). Using this formula, a length of about 155 centimeters of  18 Oxygen gas at STP (300K temperature and  1  atm pressure) is necessary to completely absorb a proton beam having energy of 12.5 MeV. By increasing the pressure to 20 atm, the necessary length at 300K becomes about 7.75 centimeters.  
                           TABLE 2                                       Proton Stopping Power For           Proton Energy (MeV)   Oxygen gas (gm/cm 2 )                                                    4.5   0.03738           5   0.04479           5.5   0.05278           6   0.06134           6.5   0.07047           7   0.08015           7.5   0.09039           8   0.10118           8.5   0.1125           9   0.12435           9.5   0.13674           10   0.14964           12.5   0.22181           15   0.30643           17.5   0.40308           20   0.51143           22.5   0.63119           25   0.7621           27.5   0.90392           30   1.0565           50   2.641           100   9.09                      
 
      Consequently in one preferred implementation, the chamber  200  (along with its parts) is designed to withstand high pressures, especially since higher pressures become necessary as the chamber  200  and gas heat up due to the irradiation by the proton beam. In one exemplary implementation of the inventive concept to produce  18 F-Fluoride from  18 Oxygen gas, we have demonstrated the success of using Havar with thickness of 40 microns to contain  18 Oxygen at fill pressure of 20 atm irradiated with 13 MeV proton beam (protons with 12.5 MeV transmitting into the chamber volume, 0.5 MeV being absorbed by the Havar chamber window) at a beam current of 20 microamperes. The exemplary implementation successfully contained the  18 Oxygen gas during irradiation with the proton beam and, therefore, with the  18 Oxygen gas having much higher temperatures (well over 100° C.) and pressures than the fill temperature and pressure before the irradiation. In another exemplary implementation, cooling jackets (lines) were used to remove heat from the chamber volume during irradiation. A preferred implementation would run the inventive concept at high pressures to have relatively short chamber length and thus simplify the requirements on the intensity of the incident proton beam. In alternative implementations, other suitable designs can be used to contain the  18 Oxygen gas at desired pressures.  
      The  18 F-Fluoride adheres to the chamber component  204  as it is formed. The material chosen for the at least one chamber component  204  preferably is one of which  18 F-Fluoride adheres well. The material chosen for the chamber component  204  preferably is one off of which the adhered  18 F-Fluoride dissolves easily when exposed to the appropriate 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  can be used to enhance the adherence (and/or subsequent dissolving, see later step S  1050 ) of  18 F-Fluoride.  
      In step  1040 , the unused portion of  18 Oxygen is removed from the chamber volume  201 . This can be accomplished, for example, by opening valves  501 - 503 - 505 , with the container  800  cooled to below the boiling point of  18 Oxygen. In this case, the unused portion of  18 Oxygen is drawn into the container  800  and, thus, is available for use in the next run. This step allows for the efficient use of the starting material  18 Oxygen. It is to be noted that the cooling of container  800  to below the boiling point of  18 Oxygen can be performed as the chamber volume  201  is being irradiated during step S 1030 . Such an implementation of the inventive concept reduces the run time as different steps are performed, for example, in parallel with the different segments of the looping tube  100  being isolated from each other by the various valves. The pressure of the  18 oxygen gas can be monitored by pressure gauges  303  or  301 , or both.  
      In step S 1050 , the formed  18 F-Fluoride adhered to the chamber component  204  is preferably dissolved using a solvent without taking the chamber component  204  out of the chamber  200 . This can be accomplished, for example, by opening valves  506 - 507 , while valve  505  is closed, and allowing the solvent to be introduced to the chamber volume  201 . The adhered  18 F-Fluoride is preferably dissolved by and into the introduced solvent. Step S 1050  can be augmented by heating chamber  200  so as to speed up the dissolving of the produced  18 F-Fluoride. This procedure allows the solvent to be sucked into the vacuum existing in the chamber volume  201 , thus aiding both in introducing the solvent and physically washing the chamber component  204 . Alternatively, the solvent can also be introduced due to its own flow pressure.  
      The material used as a solvent preferably should easily remove (physically and/or chemically) the  18 F-Fluoride adhered to the chamber component  204 , yet preferably easily allow the uncontaminated separation of the dissolved  18 F-Fluoride. It also preferably should not be corrosive to the system elements with which it comes into contact. Examples of such solv ents include, but are not limited to, water in liquid and steam form, acids, and alcohols.  19 Fluorine is preferably not the solvent—the resulting mixture would have  18 F- 19 F molecules that are not easily separated and would reduce, therefore, the yield of the produced ultimate  18 F-Fluoride based compound.  
      TABLE 3 shows the various percentages of the produced  18 F-Fluoride extracted using water at various temperatures. It is seen that a chamber component made from Stainless Steel yields 93.2% of the formed  18 F-Fluoride in two washes using water at 80° C. Glassy Carbon, on the other hand, yields 98.3% of the formed  18 F-Fluoride in a single wash with water at 80° C. the wash time was on the order of ten seconds. Using water at higher temperatures is expected to improve the yield per wash. Steam is expected to perform at least as well as water, if not better, in dissolving the formed  18 F-Fluoride. Other solvents may be used instead of water, keeping in mind the objective of rapidly dissolving the formed  18 F-Fluoride and the objective of not diluting the Fluorine based ultimate compound.  
                               TABLE 3                       Material of   % Recovered   % Recovered   Total %           Chamber   in   in   Recovered   Wash       Component   1 st  Wash   2 nd  Wash   in 2 Washes   Temp ° C.                                                    Ni-plated A1   66.4   7.4   73.8   80       Ni-plated A1   42.9   6.8   49.7   60       Ni-plated A1   34.4   4.4   38.8   20       Stainless Steel   80.6   12.6   93.2   80       Aluminum   5.6   1.8   7.5   80       Glassy Carbon   64.1   22.9   87.0   20       Glassy Carbon   98.3   N.A.   98.3   80                  
 
      In step  1060 , the formed  18 F-Fluoride is separated from the solvent. This can be accomplished, for example, by closing valve  507  and opening valves  512 - 505 - 506 - 509  and having bi-directional valve  513  point to waste outlet  703 . This allows the Helium to push the solvent along with the dissolved  18 F-Fluoride out of the chamber volume  201  and towards the separator  1000 . The separator  1000  separates the formed  18 F-Fluoride from the solvent, retains the formed  18 F-Fluoride, and allows the solvent to proceed to waste outlet  703 .  
      The separator  1000  can be implemented using various approaches. One preferred implementation for the separator  1000  is to use an Ion Exchange Column that is anion attractive (the formed  18 F-Fluoride being an anion) and that separates the  18 F-Fluoride from the solvent. For example, Dowex IX- 10, 200-400  mesh commercial resin, or Toray TIN-200 commercial resin, can be used as the separator. Yet another implementation is to use a separator having specific strong affinity to the formed  18 F-Fluoride such as a QMA Sep-Pak, for example. Such implementations for the separator  1000  preferentially separate and retain  18 F-Fluoride but do not retain the radioactive metallic byproducts (which are cations) from the solvent, thus retaining a high purity for the formed radioactive  18 F-Fluoride. Another preferred implementation for the separator  1000  is to use a filter retaining the formed  18 F-Fluoride.  
      In step  1070 , the separated  18 F-Fluoride is processed from the separator  1000 . This can be accomplished, for example, by closing valves  509 - 512  and opening valves  510 - 511  and having valve  513  point to the product outlet  704 . The Helium then directs the Eluent towards the separator  1000 ; with the Eluent processing the separated  18 F-Fluoride out of the separator  1000  and carrying it to the product outlet  704 . The Eluent used must have an affinity to the separated  18 F-Fluoride that is stronger than the affinity of the separator  1000 . Various chemicals may be used as the Eluent including, but not limited to various kinds of bicarbonates. Non-limiting examples of bicarbonates that can be used as the Eluent are Sodium-Bicarbonate, Potassium-Bicarbonate, and Tetrabutyl-Ammonium Bicarbonate. Other anionic Eluents can be used in addition to, or instead of, Bicarbonates. A user then obtains the processed  18 F-Fluoride through product outlet  704  and can use it in nucleophilic reactions, for example.  
      In step  1080 , the chamber volume  201  is dried in preparation for another run of forming  18 F-Fluoride. This can be accomplished, for example, by closing valve  511  and opening valves  512 - 505 - 506 - 508 . The Helium then is allowed to flow through the chamber volume  201  towards and out of the vent outlet  705 . Pressure gauge  301  can be used to monitor the drying of the chamber volume  201 . Alternatively, a humidity monitor integrated with the pressure gauge  301  can be used to track the drying of the chamber volume  201 . Step S 1080  can be augmented by heating chamber  200  so as to speed up its drying.  
      It is to be noted that steps S 1070  and S 1080  can be overlapped in time. This can be accomplished, for example, by having valves  512 - 505 - 506 - 508  open while valves  511 - 510  are open and while valve  509  is closed. This allows the Helium to dry the chamber volume  201  while the Eluent is being directed through and out of the separator  1000  and product outlet  704 , without pushing humidity towards the separator  702  or pushing the Eluent towards the vent outlet  705 . It is also to be noted that although Helium has been described as the gas used in directing the solvents and Eluents and drying the chamber volume  201 , the inventive concept can be practiced using any other gas that does not react with the formed  18 F-Fluoride, the solvent , the Eluent, or with materials forming the system (including the pressure gauges, the valves, the chamber, and the tubing). For example, Nitrogen or Argon can be used instead of Helium.  
      After drying the chamber volume  201  from solvent remnants, the system is ready for another run for producing a new batch of  18 F-Fluoride. The amount of  18 Oxygen in container  800  can be monitored to determine whether topping-off is necessary. The overall process can then be repeated starting with step S  1010 .  
      Demonstration runs of the inventive concept have consistently yielded at least about 70% of the theoretically obtainable  18 F-Fluoride from  18 O gas. The setup had a chamber volume of about 15 milliliters, the  18 Oxygen gas was filled to about pressure of 20 atmospheres, the proton beam was 13 MeV having beam current of 20 microamperes, the solvent was de-ionized with volume of 100 milliliters and a QMA separator was eluted with 2×2 milliliters of Bicarbonate solution. Such a result is especially important because  18 Oxygen in gaseous form has 14-18% better yield than  18 O-enriched water because the Hydrogen ions in the  18 O-enriched water reduce the exposure of the  18 Oxygen to the proton beam. This yield difference increases with decreasing proton energy; the yield difference being 16%, 15.2%, 14.75%, and 14.3% at 15, 30, 50, and 100 MeV, respectively.  
      Consequently, the inventive concept produces significantly greater overall yield of  18 F-Fluoride than can be produced by  18 O-enriched water based systems. For example, running a simple (non-sweeping beam) system implementing the inventive concept at a proton current beam of 100 microamperes and energy of 15 MeV will produce about 53% greater overall yield than the complicated (sweeping beam and bigger target window) system of Helmeke running at its apparent maximum of 30 microamperes. The inventive concept can be implemented with a modification using separate chemically inert gas inlets, instead of one inlet, to perform various steps in parallel. The inventive concept can also be implemented using a valve to separate the Eluent inlet from the looping tube  100 . The looping tube  100  can be formed in different shapes including, but not limited to, circular and folding to reduce the size of the system. Cooling and/or heating devices can be used to control the temperature of the material transmitted by the looping tube  100 , for example by surrounding at least a portion of the looping tube  100  with cooling and/or heating jackets. The temperature of the looping tube  100  can be monitored by thermocouples, for example, to better control the temperature of the transmitted material. Instead of one looping tube, parallel looping tubes can be used to increase the surface area and thus better enable heating and/or cooling the transmitted different material (gas/Eluent/solvent) by cooling and/or heating devices surrounding the looping tube. The chamber, and its different parts, can be formed from various different suitable designs and materials: This can be done to permit increasing the incident proton beam currents, for example. Although the present invention has been described in considerable detail with reference to certain exemplary embodiments, it should be apparent that various modifications and applications of the present invention may be realized without departing from the scope and spirit of the invention. All such variations and modifications as would be obvious to one skilled in the art are intended to be included within the scope of the claims presented herein.