Abstract:
The present invention provides systems and methods for the “in-target” reactions of radioisotopes with various reactants in order to form desired reaction products in useful states. One embodiment of the invention provides a target-holding assembly for use with a gas target and a particle accelerator configured to provide a high-energy beam along a beam axis. The target-holding assembly has a mounting portion attachable with the particle accelerator in alignment with the beam axis. A gas target holder is connected to the mounting portion and has a thermally conductive holder body with a target cavity therein configured to be in axial alignment with the beam axis. The target cavity is shaped and sized to fully contain the gas target therein for bombardment by the high-energy beam. The target body has an inlet port in fluid connection with the target cavity. The target body has a cooling channel formed therein adjacent to and isolated from the target cavity, and the cooling channel has an inlet coupleable to a cooling fluid source.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]    Reference is made and priority claimed to U.S. Provisional Patent Application entitled PARTICLE ACCELERATOR ASSEMBLY WITH HIGH POWER GAS TARGET, filed May 13, 2002, bearing application serial No. 60/380,553, which is incorporated herein by reference. 
     
    
     
       TECHNICAL FIELD  
         [0002]    The present invention is directed to components for use with particle accelerator assemblies, and more particularly, to target-holding assemblies used in the production of selected radioisotopes.  
         BACKGROUND  
         [0003]    Biologically active radiochemicals containing radioisotopes have been used for medical research as well as for therapeutic and diagnostic procedures. The incorporation of radioisotopes having short half-lives into a variety of radiochemicals has led to the possibility of imaging and quantifying biological activities in various tissues. The efficacy of the diagnostic procedure is dependent on the specific activity of the radiochemical as well as its purity. In order to produce isotopes of high specific activity, small volume targets of separated isotopes are used in the production processes. The production process for small volumes of separate isotopes can be very expensive. The economic feasibility of the production of the radiochemicals depends on the efficiency of the production process. Targets are necessary that can operate with small volumes of the separated isotopes capable of absorbing high power beams to increase the production rates to acceptable levels. The targets also must allow for efficient removal of the desired radioisotopes after their production.  
           [0004]    Various groups have used gaseous targets, in which “in-target” synthesis of radiochemicals or their precursors is conducted. The radioisotope produced during the bombardment of the target material must then be recovered for subsequent use. The use of target holders for gaseous targets on low-energy accelerators, such as the EBCO TR14 cyclotron in which beam currents of protons and deuterons of up to 1 mA are available, raises special problems. Target holder geometries are required that permit their operation when they are bombarded with high power, low-energy beams. The bodies of the target holders must be able to heat up and cool down rapidly to facilitate in target processes that involve a short-lived radioisotope. The target bodies must also be able to withstand the high pressures developed during the bombardment due to beam heating of the gas target. Finally the target holders must be made of materials that do not chemically combine with the isotopes generated in the target holder.  
         SUMMARY OF THE INVENTION  
         [0005]    The present invention provides an assembly with a target-holding assembly for holding gas targets that overcomes the problems outlined above and experienced in the prior art. One embodiment of the invention provides a target-holding assembly for use with a particle accelerator that provides a high-energy beam along a beam axis. The target-holding assembly has a mounting portion attachable to the particle accelerator in alignment with the beam axis. A gastarget holder is connected to the mounting portion and has a thermally conductive holder body with a target cavity therein configured to be in axial alignment with the beam axis. The target cavity is shaped and sized to fully contain the gas target therein for bombardment by the high-energy beam. The target body has an inlet port in fluid connection with the target cavity. The target body has a cooling channel formed therein adjacent to and isolated from the target cavity, and the cooling channel has an inlet coupleable to a coolant source.  
           [0006]    Another embodiment provides a method for forming a radioisotope product within a target vessel. The method includes placing a gaseous target within the target vessel and irradiating the gaseous target within the target vessel to form a radioisotope. A reactant is placed within the target vessel to react with the radioisotope. The reactant reacts with the radioisotope to form the radioisotope product within the target vessel, and the radioisotope product is then removed from the target vessel. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]    [0007]FIG. 1 is a schematic representation of a particle accelerator assembly with a target-holding assembly in accordance with an embodiment of the present invention.  
         [0008]    [0008]FIG. 2 is an enlarged side elevation view of the target-holding assembly of FIG. 1.  
         [0009]    [0009]FIG. 3 is an enlarged cross-sectional view of the target-holding assembly taken substantially along the lines  3 - 3  of FIG. 2.  
         [0010]    [0010]FIG. 4 is an enlarged elevational end view of the target-holding assembly of FIG. 2 viewed from the downstream end of the target-holding assembly.  
         [0011]    [0011]FIG. 5 is a flow chart diagram illustrating a process for the in-target production of a radioisotope in accordance with one embodiment of the present invention. 
     
    
     DETAILED DESCRIPTION  
       [0012]    In the following detailed description, certain specific details are set forth in order to provide a thorough understanding of various embodiments of the invention. However, one skilled in the art will understand that the invention may be practiced without these specific details. In other instances, well-known structures associated with particle accelerators have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the invention.  
         [0013]    A particle accelerator assembly  10  having a target-holding assembly  12  for holding a gaseous target  13  in accordance with one embodiment of the present invention is illustrated in the figures. As best seen in FIG. 1, the particle accelerator assembly  10  includes a cyclotron  14  that directs a proton beam along a beam axis  16  through an output port  18  to the target-holding assembly  12 . The target-holding assembly  12  contains the selected gaseous target  13  in a position to be irradiated by the proton beam to create a selected radioisotope.  
         [0014]    In one embodiment, the cyclotron  14  is a negative ion cyclotron, such as the TR19 Cyclotron produced by Ebco Technologies of Richmond, British Columbia, Canada. The TR19 Cyclotron is a low-energy particle accelerator capable of providing proton beams with currents of 100 μA at energies between 13 and 19 MeV. Other low-energy cyclotrons provided by Ebco Technologies provide proton beams with currents in excess of 2 mA on target, which can be ideal for the production of isotopes on solid targets such as Pd-103 for bracchiotherapy. The Ebco Technologies cyclotrons are ideal for the production of radioisotopes such as Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18 and other short-lived positron-emitting isotopes for the synthesis of various radiochemicals, such as fluorodeoxyglucose (FDG).  
         [0015]    As best seen in FIG. 2, the output port  18  of the cyclotron  14  has a receiving portion  20  that removably retains the target-holding assembly  12  in axial alignment with the beam axis  16 . The target-holding assembly  12  has a mounting portion  22  that extends into and connects to the cyclotron&#39;s receiving portion  20  in a quick-disconnect manner.  
         [0016]    [0016]FIG. 3 is an enlarged cross-sectional view of the target-holding assembly  12  taken substantially along line  3 - 3  of FIG. 2. The mounting portion  22  is a substantially cylindrical member having a central aperture  24  axially aligned with the beam axis  16  and sized so the mounting portion does not interfere with the proton beam passing into the target-holding assembly  12 . The mounting portion  22  has a substantially flat engagement surface  26  facing away from the receiving portion  20 , and an intermediate flange  28  is securely fastened to the engagement surface  26 . The intermediate flange  28  also has a central aperture  30  axially aligned with the mounting portion&#39;s central aperture  24  and sized so the intermediate flange does not interfere with the proton beam. In the illustrated embodiment, a first thin, foil window  32  is sandwiched between the intermediate flange  28  and the mounting portion&#39;s engagement surface  26  and extends across the central aperture  24 . The first foil window  32  provides a thin, yet strong barrier through which the proton beam passes on its way into the target-holding assembly  12 . An O-ring  34  is also sandwiched between the intermediate flange  28  and the mounting portion  22  so as to sealably engage the foil window  32  around the central aperture  24 . Accordingly, the foil window  32  and the O-ring  34  form a vacuum seal between the mounting portion&#39;s central aperture  24  and the intermediate flange&#39;s central aperture  30 .  
         [0017]    The side of the intermediate flange  28  opposite the mounting portion  22  is securely fastened to the entrance flange  36 . The entrance flange  36  has a central aperture  38  coaxially aligned with the beam axis  16  and with the other central apertures  24  and  30 . In the illustrated embodiment, a second thin, foil window  40  and an O-ring seal  42  are sandwiched between the entrance flange  36  and the intermediate flange  28 . The second foil window  40  extends across the entrance flange&#39;s central aperture  38  to form a seal between the entrance flange  36  and the intermediate flange  28 . The first and second foil windows  32  and  40  are spaced apart to define a sealed separation volume  41  that isolates the cyclotron  14  from the gaseous target  13  contained in the target-holding assembly  12 , discussed in greater detail below. In the illustrated embodiment, the foil windows  32  and  40  are made of Havar, which is an inert material having a high tensile strength and a thickness of only 0.001 inch. Alternative embodiments can have foil windows made of other inert materials or of other thicknesses that will withstand the pressures developed in the target-holding assembly  12  while also allowing the proton beam to pass through them without seriously degrading the energy of the beam.  
         [0018]    When the proton beam passes through the separation volume  41  and through the first and second foil windows  32  and  40 , the foil windows are heated by the proton beam. The intermediate flange  28  has a series of ports  44  coupled to cooling gas connectors  46  that direct a flow of inert cooling gas, such as hydrogen, helium, or argon, into the central aperture  30  of the intermediate flange  28 . In the illustrated embodiment, the intermediate flange  28  has six ports  44  in fluid communication with the central aperture  30 . The ports  44  direct the inert cooling gas onto the foil windows  32  and  40  to prevent overheating of the windows during proton beam bombardment of the gaseous target  13 .  
         [0019]    The entrance flange  36  includes a body portion  48  and an integral, thin stainless steel connection tube  50  extending away from the body portion. The body portion  48  engages the intermediate flange  28 , and the connection tube  50  is connected to a target body  52  of the target-holding assembly  12 . The entrance flange  36 , and particularly the stainless steel connection tube  50 , helps limit heat transfer from the target body  52  to the intermediate flange  28  and the mounting portion  22  during the irradiation of the gaseous target  13 . In the illustrated embodiment, the connection tube  50  has a diameter of approximately 1 cm, a length of approximately 1 cm, and a wall thickness of 0.30 cm, such that the heat conduction from the target body  52  through the connection tube  50  is less than approximately 20 watts when the gaseous target  13  is heated to approximately 500° C. The target body  52  is an elongated, thermally conductive body having an internal, tapered target cavity  54  axially aligned with the connection tube  50  and the beam axis  16 . The target cavity  54  has a partial conical shape that tapers radially inwardly from a larger diameter at the distal end  60  of the target body  52  to a smaller diameter at the proximal end  62  adjacent to the entrance flange  36 . The tapered shape of the target cavity  54  is configured to accommodate the disbursement of the high-energy beam that occurs when the particle beam bombards the gaseous target  13 , thereby allowing for maximum use of the particle beam energy within the target cavity to create a selected radioisotope.  
         [0020]    In the illustrated embodiment, the target body  52  is made of copper, which is highly thermally conductive to efficiently carry heat away from the gaseous target  13  when the target is being irradiated. The copper material also allows the target body  52  to quickly cool down or heat up as desired during the process of an in-target reaction, thereby allowing for a quick and efficient recovery of the radioisotopes from the target-holding assembly  12 . Alternate embodiments can have a target body  16  made of silver or other material that is highly thermally conductive and chemically inert for selected processes of the in-target reactions.  
         [0021]    As best seen in FIG. 3, the target body  52  has an interior surface  56  that defines the target cavity  12 . The interior surface  57  of the illustrated embodiment is plated with a thin layer of chemically inert material, such as nickel, that will not affect “in-target” reactions conducted in the target cavity  54 . Alternate embodiments, however, can use other chemically inert materials to form the interior surface  57  that defines the tapered target cavity so the interior surface will not chemically react with the gaseous target  13 , the radioactive products produced during the bombardment of the gaseous target, or the products of other in-target reactions.  
         [0022]    The target body  52  has an inlet port  56  and an outlet port  58  in fluid communication with the target cavity  54 . The inlet and outlet ports  56  and  58  are configured to direct the gaseous target  13  or other fluids into and out of the target cavity  54 . In the illustrated embodiment, the inlet port  56  extends through the proximal end  62  of the target body  52 , and the outlet port  58  is positioned at the distal end  60  of the target body  52 . The inlet and outlet ports  56  and  58  in alternate embodiments can be provided at different locations on the target body  52 . The inlet and outlet ports  56  and  58  can also be used to direct the gases or liquids into and out of the target cavity  54  for use in the in-target reactions with the radioisotope products of the bombardment.  
         [0023]    An example of such a process would be the introduction of a reactant, such as hydrogen (H 2 ) in helium (He), into the target cavity  54  through the inlet port  56  for the production of HF within the target cavity  54  in which Oxygen-18 (0-18) gas is bombarded to produce the radioisotope Flourine-18 (F-18). Another example of a different process for removal of the radioisotope of Fluorine would be the introduction of water into the target body to wash off the F-18 isotope deposited on the interior surface  57  of the target body  52  defining the target cavity  54 . The resulting product from the reactant and the radioisotope can then be easily and quickly removed from the target cavity  54  through the outlet port  58 .  
         [0024]    When the gaseous target  13  is introduced into the target cavity  54  through the inlet port  56  and bombarded with the proton beam, the temperature of the gaseous target  13  and the target body  52  significantly and quickly increases due to beam heating. This temperature increase is also accompanied by a significant pressure increase in the target cavity  54 . It is highly desirable to keep the temperature of the gaseous target  13  and the target body  52  low during the bombardment, and to allow the bombarded gaseous target and target body  52  to cool as quickly as possible for subsequent processing. The thermally conductive copper target body  52  allows for very efficient heat transfer away from the target body by convection. The target body  52  also has cooling channels  64  extending generally adjacent to, yet isolated from, the target cavity  54 . The cooling channels  64  are configured to carry a flow of coolant, such as water or other fluid, through the target body  52  adjacent to the target cavity  54  to carry heat away from the target cavity and target body during and after the bombardment process. The cooling channels  64  are coupled to a coolant inlet  66  that directs the coolant into the target body  52 , and to a coolant outlet  68  that carries the coolant away from the target body. The coolant works to effectively draw heat out of the target body  52  and the gaseous target  13  in the target holding assembly  12 .  
         [0025]    In the illustrated embodiment, the cooling channels  64  include a first elongated leg  70  that connects to the coolant inlet  66  and extends along one side of the target body  52  toward the distal end  60 . A second elongated leg  72  is on the opposite side of the target body  52  and extends from the target body&#39;s distal end  60  to the proximal end  62  and connects to the coolant outlet  68 . In one embodiment, the first and second elongated legs  70  and  72  are fluidly connected by an intermediate channel portion  74  that carries the flow of coolant through the distal end portion of the target body  52  from the first elongated leg  70  to the second elongated leg  72 . In an alternate embodiment, each of the first and second legs  70  and  72  can be independent channels with its own coolant inlet  66  and coolant outlet  68  so that the flow of coolant through each leg portion can be independently controlled.  
         [0026]    [0026]FIG. 4 is an end view of the target-holding assembly  12  of FIG. 3. The target body  52 , when viewed from the distal end  60  has four elongated ridge sections  76  arranged generally in a cruciform shape around a central body portion  78  that contains the target cavity  54 . The first and second legs  70  and  72  of the cooling channels  64  are bored in two opposing ridges  80  and  82 , respectively. The other two opposing ridges  84  and  86  include elongated channels  88  extending substantially adjacent to the target cavity  54  and parallel with the cooling channels  64 . The elongated channels  88  of the illustrated embodiment are configured to removably receive thermal elements that provide heating and/or cooling directly to the thermally conductive target body  52 . In the illustrated embodiment, the elongated channels  88  are heating channels configured to removably receive resistive heating elements  90  that can quickly heat the target body  52  and the contents in the target cavity  54 , such as during an “in-target” reaction that provides the radioisotopes in an easily extractable condition for removal from the target body  52 .  
         [0027]    In one embodiment a gaseous target  13 , such as O-18 gas, is bombarded to create the F-18 isotope, and the F-18 isotope is occluded to the surface  57  of the target cavity  54 . The gaseous target  13  and the target body  52  are cooled by the flow of coolant through the cooling channels  64  during the bombardment. Any remaining O-18 (which is very expensive) in the target cavity  54  is easily recovered through the outlet port  58  for use in subsequent applications. Water is then pumped into the target cavity  54  through the inlet port  56 . The heating elements  90  in the elongated channels  88  of the target body  52  are activated to quickly heat the water and F-18 isotope. Helium gas is then bubbled via the inlet port  56  through the heated water into the target cavity  54 , which creates an in-target reaction with the F-18 isotope, thereby resulting in HF gas that includes the F-18 isotope. The HF gas is then easily removed from the target cavity  54  via the outlet port  58  to readily and efficiently obtain the desired radioisotope in a usable form or for synthesizing to provide a selected radiochemical, such as fluorodeoxyglucose (FDG), for use in medical procedures or the like.  
         [0028]    In one embodiment, the cooling channels  64  can also be used to carry heated water or other high-temperature fluids when desired to help heat the target body  52  for the in-target reaction. Alternate embodiments of the target body  52  may have a different number or lengths of channels  64  and  88  for cooling and/or heating of the thermally conductive target body. Such variations may be required to take into account the changing conditions arising as a result of the use of other target gases and of a variety of bombarding particle beams of different energies and intensities.  
         [0029]    The illustrated embodiment allows the bombardment of a variety of gases in an efficient and effective manner at relatively high beam currents. The efficient heating and cooling of the target body  52  allows for the filling and emptying of the target cavity  54  with a variety of gases and liquids that will allow various chemical reactions to be carried out in the target body. Heating can facilitate the release of gases such as F2 produced in the bombardment. Heating also permits in-target reactions to be carried out in the target cavity  54  to produce various radioactive compounds such as HF that can be used directly or as precursors in a radiochemical synthesis process.  
         [0030]    In accordance with one embodiment, the target-holding assembly  12  (FIG. 1) is designed to enable the bombardment of O-18 gas with beam currents of up to 100 μA in order to achieve a high production rate of F-18 isotope. Such a target-holding assembly  12  requires the ability to operate the target cavity  54  at high pressures to achieve the density necessary to achieve maximum yield of F-18 isotope. Operation at such high pressures would additionally require sufficient cooling of the target body  52  (FIG. 3) to prevent either a further increase in pressure, or a degradation of the integrity of the target cavity  54  (FIG. 3), either of which may increase a risk of failure of the foil window  40  (FIG. 3). Accordingly, sufficient cooling is provided by the flow of coolant through the cooling channels  64  during the bombardment process.  
         [0031]    [0031]FIG. 5 is a flow chart showing an illustrative process for the in-target production of the F-18 isotope in HF gas. The process includes a step  102  wherein the target cavity  54  (FIG. 3) is evacuated. In step  104 , the target cavity  54  (FIG. 3) is filled with O-18 gas to an appropriate density through the inlet port  56  (FIG. 3). In accordance with the present embodiment, an appropriate density of O-18 gas is 1.42·10 −3  g/cm 2  for an energy range from the particle beam of 15 MeV. The pressure of the gaseous target  13  will be at least 17 At (250 psig) and the target cavity  54  should be designed to support pressures up to 30 At (450 psig) to allow for the localized heating of the gaseous target  13  during bombardment and resulting decrease in target density. The interior surface  57  (FIG. 3) defining the target cavity  54  is formed by nickel or another inert material suitable for the occlusion of F-18 isotope generated when the O-18 gas is bombarded.  
         [0032]    In step  106 , the target cavity  54  (FIG. 3) is bombarded by a high energy proton beam along the beam axis  16  resulting in the creation and occlusion of the F-18 isotope on the interior surface  57  (FIG. 3) of the target cavity. In order to achieve a high production rate of F-18 isotope, proton beam energies of 40 to 100 pA should be used in the bombardment. During the bombardment, the temperature of the gaseous target  13  (FIG. 3) will be controlled by the flow of coolant through the cooling channels  64  (FIG. 3) to prevent overheating of the gaseous target and the target body  52 . Then in step  108 , the O-18 gas remaining in the target cavity  54  (FIG. 3) after bombardment by the proton beam is recovered from the target cavity through the outlet port  58  (FIG. 3). In step  110 , the target cavity  54  is then filled with water through the inlet port  56 . Then in step  112 , the target body  52  (FIG. 3) is heated to approximately 500° C., for example, by using the heating elements  90  removably contained in the elongated channels  88  (FIG. 4).  
         [0033]    In step  114 , helium (He) gas containing approximately 10% hydrogen (H 2 ) gas is passed through the water in the target cavity  54  (FIG. 3) to react with the F-18 isotopes on the interior surface  57  defining the target cavity  54  to produce HF gas that includes the F-18 isotope. This “in-target” reaction can be accomplished by bubbling the helium and hydrogen gas through the water in the target cavity  54  (FIG. 3). In step  116 , the HF gas containing the F-18 isotope is then removed from the target cavity  54  (FIG. 3) through the outlet port  58 . The above exemplary embodiment is only intended to illustrate one possible in-target process. It should be understood that this is just an example of the in-target processes possible with the target-holding assembly  12  of the present invention.  
         [0034]    Although specific embodiments of, and examples for, the present invention are described herein for illustrative purposes, various equivalent modifications can be made without departing from the spirit and scope of the invention as can be recognized by those skilled in the relevant art. The teachings provided herein can be applied to other suitable materials and thicknesses, not necessarily the exemplary thicknesses and materials described herein.