WO1998022073A2 - Radionuclide production using intense electron beams - Google Patents

Radionuclide production using intense electron beams Download PDF

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Publication number
WO1998022073A2
WO1998022073A2 PCT/US1997/020921 US9720921W WO9822073A2 WO 1998022073 A2 WO1998022073 A2 WO 1998022073A2 US 9720921 W US9720921 W US 9720921W WO 9822073 A2 WO9822073 A2 WO 9822073A2
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WO
WIPO (PCT)
Prior art keywords
target material
target
electron beam
cartridge
electron
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Application number
PCT/US1997/020921
Other languages
French (fr)
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WO1998022073A3 (en
Inventor
Kenneth J. Weeks
Original Assignee
Duke University
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Publication date
Application filed by Duke University filed Critical Duke University
Priority to AU54408/98A priority Critical patent/AU5440898A/en
Publication of WO1998022073A2 publication Critical patent/WO1998022073A2/en
Publication of WO1998022073A3 publication Critical patent/WO1998022073A3/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1002Intraluminal radiation therapy

Definitions

  • the present invention relates generally to the point-of-use production of radionuclides by irradiation with intense electron beams so as to form radioactive materials suitable for therapeutic and/or diagnostic medical purposes and/or industrial applications.
  • Radioactive materials have been used extensively for many years for therapeutic and/or diagnostic medical purposes.
  • radioisotopes are used to kill large volumes of cancer cells directly using large quantities of radioactive material.
  • small amounts of radioisotopes are injected into the body or bloodstream and their position in the body is determined by observing the gamma rays emitted when they decay.
  • Radioisotopes may also be bound to some chemical which is selected for its ability to localize at a problem area in the body thereby aiding in the diagnosis of disease.
  • Relatively newer therapies propose the use of small amounts of radioactivity to treat small tissue volumes, namely intravascular walls.
  • the radioactive stent releases radiation so as to decrease the rate of proliferative cell growth of the traumatized arterial wall (i.e., to decrease intimal hyperplasia).
  • restenosis after stent implantation is expected to be significantly reduced.
  • U.S. Patent No. 5,199,939 to Dake et al the entire content of which is expressly incorporated hereinto by reference).
  • Radioisotopes While radiating tissue for medical diagnostic and/or therapeutic purposes is advantageous, there are several real and nontrivial problems associated with such Anuclear medicine®, primarily in the availability and/or accessability of the physician to a source of suitable radioactive devices and materials.
  • radioisotopes whose properties are such that they have potential value in nuclear medicine, but which cannot conventionally be produced easily in sufficiently large quantities for distribution.
  • a radioisotope has a relatively short half life (e.g., on the order of less than 24 hours), then it cannot be produced at a nuclear reactor (of which there are only a handful in the United States), verified, and shipped to an end user before the produced radioactivity has ceased.
  • Radioisotopes are therefore quite useful, but the ability to cost-effectively generate them at the Apoint-of-use@ does not presently exist, except for those facilities in sufficiently close proximity to a nuclear reactor or cyclotron. However, for those radioisotopes having a relatively long half life (e.g., greater than one week), then practically every medical site in the United States can avail themselves to such materials.
  • Radionuclides are well known and are used successfully in the medical field for purposes of cancer therapy, imaging and diagnosis of disease, as well as in assorted industrial testing and sterilization applications.
  • the conventional wisdom in the art is that nuclear reactors and cyclotrons are again necessary for production of useful radionuclides.
  • high-energy photons i.e., greater than 10 MeV
  • the present invention is directed to the methods and systems for producing radionuclides by colliding a focussed electron beam with a target material capable of being radioactivated by the electron beam.
  • the target material is translated relative to the electron beam along at least two (2) axes.
  • a target cartridge is provided according to the present invention which includes a tubular shell formed of a material which is minimally (if at all) activated by the electron beam or, if activated, has radioactivity that is very short lived in terms of minutes or less (e.g., aluminum).
  • the tubular shell defines an interior hollow space which houses the target material to be irradiated, e.g. an intraluminal stent.
  • the interior space may optionally be filled with a heat transfer fluid (e.g., water, air, an oxygen-less gas or an inert gas).
  • a heat transfer fluid e.g., water, air, an oxygen-less gas or an inert gas.
  • End caps close each end of the tubular shell and are preferably one-piece solid structures formed of the same material as that of the tubular shell. The end caps therefore most preferably serve the purposes of allowing the target cartridge to be mechanically coupled to a translator assembly and provide a path of heat transfer to a heat-transfer fluid (e.g., liquid and/or gas) in contact therewith.
  • a heat transfer fluid e.g., water, air, an oxygen-less gas or an inert gas
  • the translator assembly most preferably holds the target cartridge longitudinally so that it is positioned substantially transversely relative to the path of the electron beam.
  • the entire target cartridge may be linearly translated simultaneously or periodically sequentially parallel and perpendicular to the electron beam path.
  • the target cartridge may be rotated about its axis. In such a manner, the target cartridge exposes the target material therewithin uniformly to the electron beam.
  • FIGURE 1 is a schematic view of a preferred exemplary system according to the present invention employed for the on-site production of radionuclides
  • FIGURE 2 is a schematic perspective view, partly in section, of one embodiment of a cartridge holder for holding a desired target material to be irradiated by the electron beam generated in the system of FIGURE 1 ;
  • FIGURE 3 is a schematic view, partly in section, of another embodiment of a cartridge holder for the target material.
  • FIGURE 1 A presently preferred system 10 for obtaining radionuclides at the point-of-use is depicted schematically in accompanying FIGURE 1 as including an electron generator 12, a target translator assembly 14, a beam dump 16 and a cooling assembly 18.
  • the electron generator 12 is one part of a linear accelerator system that is conventionally employed in the medical arts for the treatment of cancer. Suitable linear accelerators that may be modified according to the present invention to form the electron generator 12 include ClinacJ Model Nos. 2100 and 1800 commercially available from Varian Corporation of Palo Alto, California.
  • the electron generator 12 is provided internally with a DC power supply 12a to provide DC power to the modulator 12b.
  • the modulator 12b is operatively connected to the electron gun 12c which injects electrons into the accelerator tube 12d and wave guide system 12e.
  • the klystron 12f is connected operatively to the accelerator 12d via the wave guide system 12e to deliver high power to the latter.
  • a magnetic steering system 12g is provided so as to focus the electron beam exiting the accelerator tube 12d into a relatively small cross-sectional area focus (e.g., an effective electron beam diameter of between about 1.0 to about 3.0 mm, and preferably between about 1.0 to about 1.5 mm).
  • the electron beam most preferably has substantially the same cross-sectional geometry as the target material which it is irradiating.
  • Circular cross-sectional geometry for the electron beam is standard, but non-circular geometries may also be employed by subjecting the beam to controllable magnetic fields (e.g., by Arelaxing@ the magnetic field along one of the beam axes relative to the magnetic field acting along the other of the beam axes).
  • the electron beam that is produced need not be continuous, and may in fact be in the form of electron beam cycles or Apackets@ per unit time. For a given number of electrons per unit time produced, however, it is preferred that more pulses per unit time of lesser intensity (i.e., greater number of electrons in each pulse) be produced.
  • the electron generator is capable of generating an electron beam energy of between about 10 MeV to about 50 MeV. More specifically, for relatively heavier isotopes, the preferred electron energy is in the range of about 15 MeV to about 20 MeV, while relatively lighter isotopes may require electron energies of about 30 MeV or greater.
  • the electron generator 12 need not have a precise or exact energy spread as may be the case for therapeutic electron generators. Instead, electron energy spreads of about "10% are acceptable for purposes of the present invention.
  • the target translator assembly 14 is positioned downstream (i.e., relative to the electron beam path shown by arrows A e in FIGURE 1) and includes a linear rail assembly 14a which carries a support table 14b for reciprocal transverse movements generally horizontally perpendicular to the electron beam path A e (i.e., into and out of the plane as shown schematically by the depiction of arrow A 1 in FIGURE 1).
  • the support table 14b is moved reciprocally relative to the rail assembly 14a via a precision DC electric motor 14c.
  • the support table 14b carries an upright support column 14d laterally of the electron beam path A e and includes an adjustment shaft 14e which is linearly telescopically moveable relative to the support column 14d (i.e., in the direction of arrow A 2 shown in FIGURE 1 generally perpendicularly relative to the electron beam path A e ).
  • Motive force to the support column 14d to enable it to move reciprocally in the direction of arrow A 2 is provided via a precision reversible DC motor 14f.
  • the adjustment shaft 14e carries a precision DC electric motor 14g for concurrent movements therewith.
  • the motor 14g includes an output/drive shaft 14h depending therefrom to which is coaxially attached a target cartridge 20.
  • the motor 14g causes the shaft 14h to rotate about the shaft axis in a desired direction (e.g., in the direction of arrow A 3 in FIGURE 1) which in turn rotates the cartridge 20 relative to the impinging electron beam.
  • the target cartridge 20 contains the target material to be irradiated by the electron beam emitted by the generator 12 in a manner to be described in greater detail below.
  • the target translator 14 is thus capable of moving the target cartridge 20 along at least two axes relative to the electron beam and rotating the cartridge 20 about one of the axes. Namely, the translator 14 is capable of controlled linear movements of the target cartridge 20 into and out of the electron beam generally horizontally transverse to the electron beam path A e . The target cartridge 20 is also capable of being moved into and out of the electron beam in the direction of arrow A 2 generally vertically perpendicular relative to the beam path A e . Simultaneously with such linear movements, the translator 14 is capable of rotating the target cartridge 20 about the axis of shaft 14h. Other degrees of movement can be provided, however.
  • a further precision motor could be provided so as to oscillate the shaft 14h at an angle relative to vertical and/or relative to the beam path A e .
  • the translator 14 may be programmed to move the target cartridge 20 in precise relationship to the electron beam provided by the electron generator 12 so as to uniformly and reliably irradiate the target material within the cartridge 12 for the desired period of time. Furthermore, it can be used to selectively non-uniformly irradiate the target - e.g., make the ends of the target material more radioactive per unit length than the center.
  • the beam dump 16 is most preferably a relatively large mass of material which stops the electron beam without producing radioactivity in dangerous amounts and minimizes the photon generation from Bremsstrahlung processes. It also absorbs heat and disperses absorbed heat due to conduction.
  • the beam dump 16 is most advantageously includes a forward section 16a (i.e., disposed toward the electron generator 12) formed of a solid material having a relatively low atomic number (e.g., aluminum) so as to be insubstantially affected by the electron beam.
  • Alow atomic number® is meant a material having an atomic number (Z) less than about 30, and more preferably less than about 13.
  • a heat sump 16b is mounted rearwardly of the forward section of the beam dump 16 and is most preferably formed of a highly heat conductive solid material, e.g., copper.
  • the beam dump 16 may be in the form of a water-holding container having an ion chamber 16c submersed therein to measure radiation by recording ionization in the chamber with an electrometer (not shown).
  • the thickness of the beam dump depends on the electron energy and material. For example, the thickness of a small water beam dump is 15 cm for a 20 MeV beam, but is 6 cm for an aluminum beam dump.
  • cooling fluid e.g., a thermally conductive liquid (water) or gas (refrigerant)
  • the cooling fluid within the bath 18a is fluid-connected to a heat-transfer system (e.g., a chiller) 18b via conduit 18c.
  • the heat-transfer system 18b is also fluid connected to the electron beam dump 16 via conduit 18d. More particularly, if the beam dump 16 includes a highly heat conductive rearward heat sump 16b, then the chilled water is most preferably jacketed therearound so as to control the temperature of the beam dump 16.
  • the beam dump 16 is in the form of a water-containing chamber, then the water in the chamber is circulated to the heat-transfer system 18b via the conduit 18d. In such a manner, the target cartridge 20 and the beam dump 16 are maintained at appropriate operating temperature levels.
  • the operation of the system 10 is controlled by a conventional programmable controller 30.
  • the controller receives as one input, a signal from a coil or torroid system 32 positioned at the output of the electron beam generator 12, which is indicative of the number of electrons in the generated beam (i.e., beam current).
  • the beam dump 16 supplies the controller 30 with an electron current result which is obtained from the ion chamber 16c.
  • signals indicative of the relative positions of support table 12b and shafts 14e, 14h are supplied as inputs to the controller 30.
  • the target cartridge 20 may be removed and brought into relatively close proximity to a remotely located (e.g., relative to the accelerator 12) sodium iodide detector 34 which records the photons emitted by the radioactive nature of the material in a fixed unit of time of counting.
  • the controller 30 includes a multichannel analyzer which sorts the photon energies according to their energy. The controller 30 thus is capable of identifying the pattern of photon energy emission as the particular radioactive element via comparison to standard patterns. The controller 30 quantifies the obtained activity or strength of the radiation relative to previous calibrations and stores the result and history of the irradiation.
  • the information may then be used to plan for another irradiation at a later time so as to take the target material within the cartridge 20 to an exact level of custom activity in as short of period of time as possible.
  • This control enables uniform or a particular pattern of non-uniform activation of a target material.
  • the controller 30 is interfaced to the electron beam generator 12 and the motors 14c, 14f and 14g so that precise control may be exercised 7 7
  • the entire system is most preferably enclosed within a shield structure (not shown) so as to shield adjacent persons from the inevitable inadvertent production of photons and neutrons.
  • the shield structure is most preferably lead, tungsten, depleted uranium and/or concrete which are fabricated according to known techniques.
  • the target cartridge 20 includes a central tubular body shell 20a having an exterior wall 20a ! which defines an interior space 20a 2 .
  • the material from which the tubular shell 20a is fabricated is preferentially a low atomic number material and a good heat conductor. Aluminum is particularly preferred since it does not activate at electron beam energies under 15 MeV and is a satisfactory heat conductor.
  • Other materials which can be used to form the tubular shell 20a include copper, stainless steel, quartz and titanium.
  • the wall 20a ! of the tubular shell 20 must also be sufficiently thin to allow electrons to pass into the interior space 20a 2 , but be sufficiently thick to impart structural rigidity and integrity to the shell 20.
  • thicker (e.g., in terms of g/cm 2 ) walls of the shell 20 will result in relatively longer activation times for the target material and vice versa.
  • a balance between the thickness of wall 20a ! and the activation time of the target material contained therewithin must be made.
  • the thickness of wall 20a should not exceed about 1.50 mm, and preferably should be between about 0.10 and about 0.50 mm.
  • Each end of the tubular shell 20a is closed by a solid end cap 20b.
  • the end caps 20b, 20c can be fabricated from any material which has sufficient mass and conducts heat well, but preferably the end caps 20b, 20c are fabricated from the same material as the tubular shell 20a, namely, aluminum.
  • the end caps 20b, 20c serve to close each end of the tubular shell 20a and allow the entire target cartridge 20 to be mechanically coupled longitudinally to the shaft 14h (see FIGURE 1) via threads, clamp structures, bolts and the like.
  • At least one of the end caps 20c carries a coaxially positioned rigid core element 20d around which a length of the target material 22 to be irradiated by the electron beam may be helically wrapped.
  • the core element 20d provides support for the target material 22 carried thereby and most preferably is formed of a high-melting point material so it is unaffected by the heat generated during irradiation, e.g., tungsten.
  • the target material 22 may be in virtually any desired structural shape.
  • the target material 22 may be in the form of a helical stent without a core 20d and/or may be in the form of a wire mesh wrapped around the core 20d to thereby allow for the creation of intricate radioactive structures.
  • At least one, and more preferably both, of the end caps 20b, 20c are removably coupled to the tubular shell 20a, preferably by threaded interengagement, to allow access to the interior space 20a 2 (e.g., so as to allow removal of the irradiated target material 22).
  • the interior space 20a 2 of the tubular shell 20a may optionally be 73
  • a circulating fluid medium which is chemically compatible with the target material under electron beam irradiation conditions (e.g., water, air, oxygen-less gas, or inert gas) which facilitates thermal contact between the target material wire 22 and the tubular shell 20a and end caps 20b, 20c and serves to dissipate heat therefrom.
  • the fluid medium may be introduced into and withdrawn from the shell 20 via suitable coolant inlet/outlet ports. If the shell 20 is sealed - e.g., if a circulating fluid medium is not employed -- then it is preferred that the interior space within the shell 20 be evacuated or be filled with an inert gas.
  • tubular shell 20a Although a right cylindrical configuration is depicted in FIGURE 2 for the tubular shell 20a, virtually any tubular cross-sectional geometries may be employed as the shell 20a in the practice of this invention. Thus, tubular shells having a rectangular, pentagonal, hexagonal and the like geometry may be employed. Also, a tubular shell having an elliptical cross-section may be employed, in which case it is preferred that the major axis of the shell be presented to the electron beam. In addition, the tubular shell need not have a linear central axis, but instead may be bent or curved. The only real constraint is a shape that has a thin wall. In certain modifications, there is no wall at all.
  • target cartridge 20' is depicted in FIGURE 3 and is structurally similar to target cartridge 20 depicted in FIGURE 2, except that no core element 20d is provided.
  • the target cartridge 20' is especially adapted to accept target material 24 in the form of straight wires, shells, meshes, relatively short lengths of random or regular wire, particulate material (e.g., powders) and the like.
  • the target material may be loaded into the interior space 20a 2 ' in a regular pattern as shown in FIGURE 3, or may be randomly positioned therewithin.
  • the target material may be virtually any material which produces a radioactive isotope when bombarded by an electron beam having a beam energy between about 10 to about 50 MeV.
  • Exemplary elements that may be used as target materials in the target cartridges described above include Br, Lu, Ta, Re, Ir, C, F, P, Sc, Cu, Zn, Pt, Ga, Ni, Te, Pm, Ho, Yb, Ta and Au. If the target material is in the form of an intraluminal stent, then nickel, tantalum, platinum and rhenium are particularly preferred.
  • radioisotopes which can be formed according to the present invention include 83 Br , 179 Lu, 183 Ta, 189 Re, 194 lr, 195 lr, 11 C, 18 F, 30 P, 44 Sc, 62 Cu, 64 Cu, 63 Zn, 68 Ga, 57 Ni, 127 Te, 129 Te, 140 Pm, 16 Ho, 175 Yb, 179 Lu, 180 Ta, 184 Re, 186 Re, and 196 Au.
  • a wire mesh of tantalum (Ta) as the target material was wrapped around an aluminum core of a target cartridge depicted in FIGURE 2 having a 1.0 mm diameter x 15 mm length so that the mesh had a nominal diameter of about 1.2 mm.
  • the wire diameter of the Ta mesh was such that the mesh size was about 0.1 mm.
  • the tubular shell which contained the core and wire mesh was formed from aluminum and had an 75
  • the end caps of the tubular shell were made of one piece solid aluminum with a diameter of about 12.5 mm and lengths of 25 mm and 38 mm, respectively.
  • the larger diameter and greater length of the end caps relative to the tubular shell added thermal mass to the target cartridge thereby reducing the heat requirements.
  • the target cartridges in accordance with the present invention may include a tubular shell with end caps that serve to provide nominal closure to the interior space of the shell.
  • the target cartridge may therefore be designed to be placed or loaded within a cartridge holder having the appropriate mass and structural integrity at its ends to serve the purpose of the end caps described above (e.g., for mounting and thermal transfer purposes).

Abstract

Radionuclides are produced by colliding a focussed electron beam with a target material (22). The target cartridge (20) includes a tubular shell formed of a material which is minimally activated by the electron beam (e.g. aluminum). The tubular shell defines an interior hollow space which houses the target material (22) to be irradiated. End caps (20b, 20c) close each end of the tubular shell and are preferably one-piece solid structures formed of the same material as that of the tubular shell. The end caps allow the target cartridge (20) to be mechanically coupled to a translator assembly (14) and provide a path of heat transfer to a heat-transfer fluid. The entire target cartridge (20) may be linearly translated simultaneously or periodically sequentially parallel and perpendicular to the electron beam path. At the same time, the target cartridge (20) may be rotated about its axis.

Description

RADIONUCLIDE PRODUCTION USING INTENSE ELECTRON BEAMS
FIELD OF INVENTION
The present invention relates generally to the point-of-use production of radionuclides by irradiation with intense electron beams so as to form radioactive materials suitable for therapeutic and/or diagnostic medical purposes and/or industrial applications.
BACKGROUND AND SUMMARY OF THE INVENTION
Radioactive materials have been used extensively for many years for therapeutic and/or diagnostic medical purposes. In this regard, radioisotopes are used to kill large volumes of cancer cells directly using large quantities of radioactive material. Alternatively, small amounts of radioisotopes are injected into the body or bloodstream and their position in the body is determined by observing the gamma rays emitted when they decay. Radioisotopes may also be bound to some chemical which is selected for its ability to localize at a problem area in the body thereby aiding in the diagnosis of disease.
Relatively newer therapies propose the use of small amounts of radioactivity to treat small tissue volumes, namely intravascular walls. For example, U.S. Patent No. 5,059,166 to Fischell et al (the entire content of which is incorporated hereinto by reference) discloses a stent formed of a radioactive material having a half-life between 10 hours and 100 days which may be embedded into plaque tissue within a patient=s arterial wall. The radioactive stent releases radiation so as to decrease the rate of proliferative cell growth of the traumatized arterial wall (i.e., to decrease intimal hyperplasia). As a result of such radiation therapy, restenosis after stent implantation is expected to be significantly reduced. See also in this regard, U.S. Patent No. 5,199,939 to Dake et al (the entire content of which is expressly incorporated hereinto by reference).
While radiating tissue for medical diagnostic and/or therapeutic purposes is advantageous, there are several real and nontrivial problems associated with such Anuclear medicine®, primarily in the availability and/or accessability of the physician to a source of suitable radioactive devices and materials. In this regard, there exist many radioisotopes whose properties are such that they have potential value in nuclear medicine, but which cannot conventionally be produced easily in sufficiently large quantities for distribution. Associated with this is the practical problem that if a radioisotope has a relatively short half life (e.g., on the order of less than 24 hours), then it cannot be produced at a nuclear reactor (of which there are only a handful in the United States), verified, and shipped to an end user before the produced radioactivity has ceased.
Radioisotopes are therefore quite useful, but the ability to cost-effectively generate them at the Apoint-of-use@ does not presently exist, except for those facilities in sufficiently close proximity to a nuclear reactor or cyclotron. However, for those radioisotopes having a relatively long half life (e.g., greater than one week), then practically every medical site in the United States can avail themselves to such materials.
Radionuclides are well known and are used successfully in the medical field for purposes of cancer therapy, imaging and diagnosis of disease, as well as in assorted industrial testing and sterilization applications. However, the conventional wisdom in the art is that nuclear reactors and cyclotrons are again necessary for production of useful radionuclides. However, it is known that high-energy photons (i.e., greater than 10 MeV) can activate materials primarily via the (g, n) and (g, p) reactions. However, even when such a technique is disclosed, it is often minimized as a useful production method. See in this regard, Production of Radionuclides, Physics in Nuclear Medicine, 2nd edition, J.A. Sorenson and M.E. Phelps, Arne and Shatton, Inc., Orlando (1987), p 151 (incorporated hereinto by reference).
It would therefore be highly desirable if a cost-effective reliable technique were proposed which would enable virtually any facility in need of radionuclide the ability to produce the same Aon-site@. It is towards fulfilling such a need that the present invention is directed.
Broadly, the present invention is directed to the methods and systems for producing radionuclides by colliding a focussed electron beam with a target material capable of being radioactivated by the electron beam. In preferred embodiments, the target material is translated relative to the electron beam along at least two (2) axes. In this regard, a target cartridge is provided according to the present invention which includes a tubular shell formed of a material which is minimally (if at all) activated by the electron beam or, if activated, has radioactivity that is very short lived in terms of minutes or less (e.g., aluminum). The tubular shell defines an interior hollow space which houses the target material to be irradiated, e.g. an intraluminal stent. The interior space may optionally be filled with a heat transfer fluid (e.g., water, air, an oxygen-less gas or an inert gas). End caps close each end of the tubular shell and are preferably one-piece solid structures formed of the same material as that of the tubular shell. The end caps therefore most preferably serve the purposes of allowing the target cartridge to be mechanically coupled to a translator assembly and provide a path of heat transfer to a heat-transfer fluid (e.g., liquid and/or gas) in contact therewith.
The translator assembly most preferably holds the target cartridge longitudinally so that it is positioned substantially transversely relative to the path of the electron beam. By suitable adjustment shafts and linear rail assemblies, therefore, the entire target cartridge may be linearly translated simultaneously or periodically sequentially parallel and perpendicular to the electron beam path. At the same time, the target cartridge may be rotated about its axis. In such a manner, the target cartridge exposes the target material therewithin uniformly to the electron beam.
These and other aspects and advantages of the present invention will become more clear after careful consideration is given to the following detailed description of the preferred exemplary embodiments thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
Reference will hereinafter be made to the accompanying drawings wherein like reference numerals throughout the various FIGURES denote like structural elements, and wherein; FIGURE 1 is a schematic view of a preferred exemplary system according to the present invention employed for the on-site production of radionuclides;
FIGURE 2 is a schematic perspective view, partly in section, of one embodiment of a cartridge holder for holding a desired target material to be irradiated by the electron beam generated in the system of FIGURE 1 ; and
FIGURE 3 is a schematic view, partly in section, of another embodiment of a cartridge holder for the target material.
DETAILED DESCRIPTION OF THE PREFERRED EXEMPLARY EMBODIMENTS
A presently preferred system 10 for obtaining radionuclides at the point-of-use is depicted schematically in accompanying FIGURE 1 as including an electron generator 12, a target translator assembly 14, a beam dump 16 and a cooling assembly 18.
The electron generator 12 is one part of a linear accelerator system that is conventionally employed in the medical arts for the treatment of cancer. Suitable linear accelerators that may be modified according to the present invention to form the electron generator 12 include ClinacJ Model Nos. 2100 and 1800 commercially available from Varian Corporation of Palo Alto, California. In essence, the electron generator 12, is provided internally with a DC power supply 12a to provide DC power to the modulator 12b. The modulator 12b is operatively connected to the electron gun 12c which injects electrons into the accelerator tube 12d and wave guide system 12e. The klystron 12f is connected operatively to the accelerator 12d via the wave guide system 12e to deliver high power to the latter. A magnetic steering system 12g is provided so as to focus the electron beam exiting the accelerator tube 12d into a relatively small cross-sectional area focus (e.g., an effective electron beam diameter of between about 1.0 to about 3.0 mm, and preferably between about 1.0 to about 1.5 mm).
The electron beam most preferably has substantially the same cross-sectional geometry as the target material which it is irradiating. Circular cross-sectional geometry for the electron beam is standard, but non-circular geometries may also be employed by subjecting the beam to controllable magnetic fields (e.g., by Arelaxing@ the magnetic field along one of the beam axes relative to the magnetic field acting along the other of the beam axes). The electron beam that is produced need not be continuous, and may in fact be in the form of electron beam cycles or Apackets@ per unit time. For a given number of electrons per unit time produced, however, it is preferred that more pulses per unit time of lesser intensity (i.e., greater number of electrons in each pulse) be produced.
Most preferably the electron generator is capable of generating an electron beam energy of between about 10 MeV to about 50 MeV. More specifically, for relatively heavier isotopes, the preferred electron energy is in the range of about 15 MeV to about 20 MeV, while relatively lighter isotopes may require electron energies of about 30 MeV or greater. The electron generator 12 need not have a precise or exact energy spread as may be the case for therapeutic electron generators. Instead, electron energy spreads of about "10% are acceptable for purposes of the present invention.
The target translator assembly 14 is positioned downstream (i.e., relative to the electron beam path shown by arrows Ae in FIGURE 1) and includes a linear rail assembly 14a which carries a support table 14b for reciprocal transverse movements generally horizontally perpendicular to the electron beam path Ae (i.e., into and out of the plane as shown schematically by the depiction of arrow A1 in FIGURE 1). The support table 14b is moved reciprocally relative to the rail assembly 14a via a precision DC electric motor 14c.
The support table 14b carries an upright support column 14d laterally of the electron beam path Ae and includes an adjustment shaft 14e which is linearly telescopically moveable relative to the support column 14d (i.e., in the direction of arrow A2 shown in FIGURE 1 generally perpendicularly relative to the electron beam path Ae). Motive force to the support column 14d to enable it to move reciprocally in the direction of arrow A2 is provided via a precision reversible DC motor 14f.
The adjustment shaft 14e carries a precision DC electric motor 14g for concurrent movements therewith. The motor 14g includes an output/drive shaft 14h depending therefrom to which is coaxially attached a target cartridge 20. The motor 14g causes the shaft 14h to rotate about the shaft axis in a desired direction (e.g., in the direction of arrow A3 in FIGURE 1) which in turn rotates the cartridge 20 relative to the impinging electron beam. The target cartridge 20 contains the target material to be irradiated by the electron beam emitted by the generator 12 in a manner to be described in greater detail below.
The target translator 14 is thus capable of moving the target cartridge 20 along at least two axes relative to the electron beam and rotating the cartridge 20 about one of the axes. Namely, the translator 14 is capable of controlled linear movements of the target cartridge 20 into and out of the electron beam generally horizontally transverse to the electron beam path Ae. The target cartridge 20 is also capable of being moved into and out of the electron beam in the direction of arrow A2 generally vertically perpendicular relative to the beam path Ae. Simultaneously with such linear movements, the translator 14 is capable of rotating the target cartridge 20 about the axis of shaft 14h. Other degrees of movement can be provided, however. For example, a further precision motor could be provided so as to oscillate the shaft 14h at an angle relative to vertical and/or relative to the beam path Ae. Thus, the translator 14 may be programmed to move the target cartridge 20 in precise relationship to the electron beam provided by the electron generator 12 so as to uniformly and reliably irradiate the target material within the cartridge 12 for the desired period of time. Furthermore, it can be used to selectively non-uniformly irradiate the target - e.g., make the ends of the target material more radioactive per unit length than the center.
The beam dump 16 is most preferably a relatively large mass of material which stops the electron beam without producing radioactivity in dangerous amounts and minimizes the photon generation from Bremsstrahlung processes. It also absorbs heat and disperses absorbed heat due to conduction. In this regard, the beam dump 16 is most advantageously includes a forward section 16a (i.e., disposed toward the electron generator 12) formed of a solid material having a relatively low atomic number (e.g., aluminum) so as to be insubstantially affected by the electron beam. By the term Alow atomic number® is meant a material having an atomic number (Z) less than about 30, and more preferably less than about 13. A heat sump 16b is mounted rearwardly of the forward section of the beam dump 16 and is most preferably formed of a highly heat conductive solid material, e.g., copper. Alternatively, the beam dump 16 may be in the form of a water-holding container having an ion chamber 16c submersed therein to measure radiation by recording ionization in the chamber with an electrometer (not shown). The thickness of the beam dump depends on the electron energy and material. For example, the thickness of a small water beam dump is 15 cm for a 20 MeV beam, but is 6 cm for an aluminum beam dump.
One end of the cartridge 20 is in thermal contact with cooling fluid (e.g., a thermally conductive liquid (water) or gas (refrigerant)) within the cooling bath 18a carried on the support table 14b associated with the cooling system 18. The cooling fluid within the bath 18a is fluid-connected to a heat-transfer system (e.g., a chiller) 18b via conduit 18c. The heat-transfer system 18b is also fluid connected to the electron beam dump 16 via conduit 18d. More particularly, if the beam dump 16 includes a highly heat conductive rearward heat sump 16b, then the chilled water is most preferably jacketed therearound so as to control the temperature of the beam dump 16. Alternatively, if the beam dump 16 is in the form of a water-containing chamber, then the water in the chamber is circulated to the heat-transfer system 18b via the conduit 18d. In such a manner, the target cartridge 20 and the beam dump 16 are maintained at appropriate operating temperature levels.
The operation of the system 10 is controlled by a conventional programmable controller 30. Specifically, the controller receives as one input, a signal from a coil or torroid system 32 positioned at the output of the electron beam generator 12, which is indicative of the number of electrons in the generated beam (i.e., beam current). The beam dump 16 supplies the controller 30 with an electron current result which is obtained from the ion chamber 16c. In addition, signals indicative of the relative positions of support table 12b and shafts 14e, 14h are supplied as inputs to the controller 30. The target cartridge 20 may be removed and brought into relatively close proximity to a remotely located (e.g., relative to the accelerator 12) sodium iodide detector 34 which records the photons emitted by the radioactive nature of the material in a fixed unit of time of counting. The controller 30 includes a multichannel analyzer which sorts the photon energies according to their energy. The controller 30 thus is capable of identifying the pattern of photon energy emission as the particular radioactive element via comparison to standard patterns. The controller 30 quantifies the obtained activity or strength of the radiation relative to previous calibrations and stores the result and history of the irradiation. The information may then be used to plan for another irradiation at a later time so as to take the target material within the cartridge 20 to an exact level of custom activity in as short of period of time as possible. This control enables uniform or a particular pattern of non-uniform activation of a target material.
The controller 30 is interfaced to the electron beam generator 12 and the motors 14c, 14f and 14g so that precise control may be exercised 7 7
over the irradiation procedure - e.g., in terms of the electron beam generated by the generator 12 and the movement protocol of the target cartridge 20.
The entire system is most preferably enclosed within a shield structure (not shown) so as to shield adjacent persons from the inevitable inadvertent production of photons and neutrons. The shield structure is most preferably lead, tungsten, depleted uranium and/or concrete which are fabricated according to known techniques.
An exemplary target cartridge 20 is depicted in FIGURE 2. Specifically, as depicted therein, the target cartridge 20 includes a central tubular body shell 20a having an exterior wall 20a! which defines an interior space 20a2. The material from which the tubular shell 20a is fabricated is preferentially a low atomic number material and a good heat conductor. Aluminum is particularly preferred since it does not activate at electron beam energies under 15 MeV and is a satisfactory heat conductor. Other materials which can be used to form the tubular shell 20a include copper, stainless steel, quartz and titanium.
The wall 20a! of the tubular shell 20 must also be sufficiently thin to allow electrons to pass into the interior space 20a2, but be sufficiently thick to impart structural rigidity and integrity to the shell 20. In this regard, as recognized by those skilled in this art, thicker (e.g., in terms of g/cm2) walls of the shell 20 will result in relatively longer activation times for the target material and vice versa. Thus, a balance between the thickness of wall 20a! and the activation time of the target material contained therewithin must be made. By way of the example, when the tubular shell 20 is formed from aluminum, the thickness of wall 20a., should not exceed about 1.50 mm, and preferably should be between about 0.10 and about 0.50 mm.
Each end of the tubular shell 20a is closed by a solid end cap 20b. The end caps 20b, 20c can be fabricated from any material which has sufficient mass and conducts heat well, but preferably the end caps 20b, 20c are fabricated from the same material as the tubular shell 20a, namely, aluminum. The end caps 20b, 20c serve to close each end of the tubular shell 20a and allow the entire target cartridge 20 to be mechanically coupled longitudinally to the shaft 14h (see FIGURE 1) via threads, clamp structures, bolts and the like.
At least one of the end caps 20c carries a coaxially positioned rigid core element 20d around which a length of the target material 22 to be irradiated by the electron beam may be helically wrapped. The core element 20d provides support for the target material 22 carried thereby and most preferably is formed of a high-melting point material so it is unaffected by the heat generated during irradiation, e.g., tungsten. The target material 22 may be in virtually any desired structural shape. Thus, for example, the target material 22 may be in the form of a helical stent without a core 20d and/or may be in the form of a wire mesh wrapped around the core 20d to thereby allow for the creation of intricate radioactive structures. At least one, and more preferably both, of the end caps 20b, 20c are removably coupled to the tubular shell 20a, preferably by threaded interengagement, to allow access to the interior space 20a2 (e.g., so as to allow removal of the irradiated target material 22).
The interior space 20a2 of the tubular shell 20a may optionally be 73
filled with a circulating fluid medium which is chemically compatible with the target material under electron beam irradiation conditions (e.g., water, air, oxygen-less gas, or inert gas) which facilitates thermal contact between the target material wire 22 and the tubular shell 20a and end caps 20b, 20c and serves to dissipate heat therefrom. As shown in FIGURE 2, the fluid medium may be introduced into and withdrawn from the shell 20 via suitable coolant inlet/outlet ports. If the shell 20 is sealed - e.g., if a circulating fluid medium is not employed -- then it is preferred that the interior space within the shell 20 be evacuated or be filled with an inert gas.
Although a right cylindrical configuration is depicted in FIGURE 2 for the tubular shell 20a, virtually any tubular cross-sectional geometries may be employed as the shell 20a in the practice of this invention. Thus, tubular shells having a rectangular, pentagonal, hexagonal and the like geometry may be employed. Also, a tubular shell having an elliptical cross-section may be employed, in which case it is preferred that the major axis of the shell be presented to the electron beam. In addition, the tubular shell need not have a linear central axis, but instead may be bent or curved. The only real constraint is a shape that has a thin wall. In certain modifications, there is no wall at all.
An alternative target cartridge 20' is depicted in FIGURE 3 and is structurally similar to target cartridge 20 depicted in FIGURE 2, except that no core element 20d is provided. (Structures associated with target cartridge 20' which are similar to those found in target cartridge 20 bear the same reference numeral, but have been further identified by a prime (>) designator.) The target cartridge 20' is especially adapted to accept target material 24 in the form of straight wires, shells, meshes, relatively short lengths of random or regular wire, particulate material (e.g., powders) and the like. The target material may be loaded into the interior space 20a2' in a regular pattern as shown in FIGURE 3, or may be randomly positioned therewithin.
The target material (e.g, reference numeral 22 in FIGURE 2 and reference numeral 24 depicted in FIGURE 3) may be virtually any material which produces a radioactive isotope when bombarded by an electron beam having a beam energy between about 10 to about 50 MeV. Exemplary elements that may be used as target materials in the target cartridges described above include Br, Lu, Ta, Re, Ir, C, F, P, Sc, Cu, Zn, Pt, Ga, Ni, Te, Pm, Ho, Yb, Ta and Au. If the target material is in the form of an intraluminal stent, then nickel, tantalum, platinum and rhenium are particularly preferred. Examples of radioisotopes which can be formed according to the present invention include 83Br , 179Lu, 183Ta, 189Re, 194lr, 195lr, 11C, 18F, 30P, 44Sc, 62Cu, 64Cu, 63Zn, 68Ga, 57Ni, 127Te, 129Te, 140Pm, 16 Ho, 175Yb, 179Lu, 180Ta, 184Re, 186Re, and 196Au.
The following non-limiting Example will further illustrate the present invention.
EXAMPLE
A wire mesh of tantalum (Ta) as the target material was wrapped around an aluminum core of a target cartridge depicted in FIGURE 2 having a 1.0 mm diameter x 15 mm length so that the mesh had a nominal diameter of about 1.2 mm. The wire diameter of the Ta mesh was such that the mesh size was about 0.1 mm. The tubular shell which contained the core and wire mesh was formed from aluminum and had an 75
inner diameter of about 2.5 mm, an length of 15 mm and a 1.0 mm wall thickness. The end caps of the tubular shell were made of one piece solid aluminum with a diameter of about 12.5 mm and lengths of 25 mm and 38 mm, respectively. The larger diameter and greater length of the end caps relative to the tubular shell added thermal mass to the target cartridge thereby reducing the heat requirements.
Experiments were conducted and indicated that the target cartridge with the Ta target material contained therein when irradiated with an electron beam having a beam power of 18 MeV electrons produced at a rate of 8 x 1014 electrons per second would, after 22 minutes of irradiation, produce a target material which was a radioactive (600 microcurie) 180Ta mesh structure.
*************
Various modifications and alternative arrangements of the present invention may be envisioned by those skilled in the art. In this regard, although the discussion above focussed on movement of the target cartridge relative to the electron beam, the target cartπdge may be fixed in position and the electron beam moved or oscillated relative thereto by means of magnetic steering fields well known in the art.
Furthermore, there are a number of well known alternate means of accelerating electrons to high energy (e.g., on the order between 10 to 50 MeV) other than the exemplary electron beam generator 12 described herein. All such means may be employed in place of the generator 12. Thus, racetrack microtrons and betatrons may be employed if beam energies between 25-50 MeV are desired. Magnetron driven machines having beam energies between 10-20 MeV could also be employed.
The target cartridges in accordance with the present invention may include a tubular shell with end caps that serve to provide nominal closure to the interior space of the shell. The target cartridge may therefore be designed to be placed or loaded within a cartridge holder having the appropriate mass and structural integrity at its ends to serve the purpose of the end caps described above (e.g., for mounting and thermal transfer purposes).
Therefore, while the present invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

Claims

WHAT IS CLAIMED IS:
1. A target cartridge for irradiation by an electron beam comprising: a tubular shell having a wall which defines an interior space; end caps closing each end of said tubular shell; and a target material capable of being radioactivated by an electron beam contained within said interior space.
2. A target cartridge as in claim 1 , further comprising a core coaxially positioned within said interior space for supporting said target material.
3. A target cartridge as in claim 1 , wherein said interior space is filled with a fluid.
4. A target cartridge as in claim 3, wherein said fluid is water, air or an inert gas.
5. A target cartridge as in claim 1 , wherein each said end piece is a one-piece solid structure.
6. A target cartridge as in claim 1 or 5, wherein at least one of said end pieces is removably coupled to said tubular shell.
7. A target cartπdge as in claim 1 , wherein said tubular shell is formed from aluminum.
8. A target cartridge as in claim 1 , wherein said target material is in 78
the form of a wire or mesh structure.
9. A target cartridge as in claim 1 , wherein said target material is in the form of particulates.
10. A target cartridge as in claim 1 , wherein said tubular shell and end caps are each formed of aluminum.
11. A target cartridge as in claim 1 , wherein said target material is at least one element selected from the group consisting of Br, Lu, Ta, Re, Pt, Ir, C, F, P, Sc, Cu, Zn, Ga, Ni, Te, Pm, Ho, Yb, Ta and Au.
12. A method of making radionuclides comprising directing a beam of electrons toward a target material, and moving the target material relative to the electron beam for a time sufficient to form radionuclides of the target material.
13. A method as in claim 12, wherein said beam of electrons has an electron energy between about 10 MeV to about 50 MeV.
14. A method as in claim 12, wherein the target material is at least one element selected from the group consisting of Br, Lu, Ta, Re, Ir, C, F, Pt, P, Sc, Cu, Zn, Ga, Ni, Te, Pm, Ho, Yb, Ta and Au.
15. A method as in claim 12, wherein said target material is exposed to said electron beam for a time sufficient to form at least one radionuclide selected from the group consisting of 83Br , 179Lu, 83Ta, 189Re, 194lr, 195lr, 11C, 18F, 30P, 44Sc, 62Cu, 6 Cu, 63Zn, 68Ga, 57Ni, 127Te, 129Te, 140Pm, 164Ho, 175Yb, 179Lu, 180Ta, 184Re, 186Re, and 196Au.
16. A method as in claim 12, wherein said target material is linearly translated along two axes which are mutually perpendicular to each other and to the electron beam.
17. A method as in claim 16, wherein said target material is rotated about said perpendicular axis.
18. A method as in claim 12, including cooling said target material.
19. A method as in claim 12, including determining the number of electrons in said beam per unit time.
20. A method as in claim 12, wherein said electrons are directed toward said target material in packets of electrons per unit time.
21. A method as in claim 12, which includes positioning an electron dump downstream of said target material.
22. A method as in claim 21 , which includes cooling said electron dump with a cooling medium.
23. A system for radioactivating a target material comprising: an electron beam generator for generating an electron beam along a beam path; and a translator assembly for holding a target material in the beam path so that said target material is irradiated with said electron beam and for translating said target mateπal relative to said beam path.
24. A system as in claim 23, wherein said translator assembly includes a support member for supporting said target material for reciprocal linear movements perpendicular to said beam path.
25. A system as in claim 23 or 24, wherein said translator assembly includes an adjustment member for supporting said target material for reciprocal linear movements substantially perpendicular to said beam path.
26. A system as in claim 25, wherein said translator assembly includes a rotatable shaft for supporting and rotating said target material relative to said beam path.
27. A system as in claim 23, further comprising a beam dump positioned downstream of said translator assembly in said beam path.
28. A system as in claim 27, wherein said beam dump includes a forward section for collecting electrons emitted by said electron generator, and a downstream heat-transfer section.
29. A system as in claim 23, further comprising a cooling system for cooling said target material during irradiation by said electron beam.
30. A system as in claim 28, further comprising a cooling system for cooling said target material and said beam dump during irradiation of said target material by said electron beam.
31. A system as in claim 23, further comprising a controller for controlling translational movement of said target material relative to said electron beam.
32. A system for radioactivating a target material comprising: an electron beam generator for generating an electron beam along a beam path; a target cartridge which includes a tubular shell containing target material to be radioactivated by said electron beam; and a translator assembly for holding said target cartπdge in the beam path so that said target material is irradiated with said electron beam and for translating said target material relative to said beam path.
PCT/US1997/020921 1996-11-05 1997-11-04 Radionuclide production using intense electron beams WO1998022073A2 (en)

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US7722662B2 (en) 1998-02-17 2010-05-25 Reva Medical, Inc. Expandable stent with sliding and locking radial elements
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US9173751B2 (en) 2004-12-17 2015-11-03 Reva Medical, Inc. Slide-and-lock stent
US8277500B2 (en) 2004-12-17 2012-10-02 Reva Medical, Inc. Slide-and-lock stent
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US9149378B2 (en) 2005-08-02 2015-10-06 Reva Medical, Inc. Axially nested slide and lock expandable device
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US7988721B2 (en) 2007-11-30 2011-08-02 Reva Medical, Inc. Axially-radially nested expandable device
US8460363B2 (en) 2007-11-30 2013-06-11 Reva Medical, Inc. Axially-radially nested expandable device
US9314354B2 (en) 2007-11-30 2016-04-19 Reva Medical, Inc. Axially-radially nested expandable device
US8545547B2 (en) 2008-10-10 2013-10-01 Reva Medical Inc. Expandable slide and lock stent
US9066827B2 (en) 2008-10-10 2015-06-30 Reva Medical, Inc. Expandable slide and lock stent
US7947071B2 (en) 2008-10-10 2011-05-24 Reva Medical, Inc. Expandable slide and lock stent
US8523936B2 (en) 2010-04-10 2013-09-03 Reva Medical, Inc. Expandable slide and lock stent
US9452068B2 (en) 2010-04-10 2016-09-27 Reva Medical, Inc. Expandable slide and lock stent
US9408732B2 (en) 2013-03-14 2016-08-09 Reva Medical, Inc. Reduced-profile slide and lock stent

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