WO1998019740A1

WO1998019740A1 - Radionuclide production using intense electron beams

Info

Publication number: WO1998019740A1
Application number: PCT/US1997/020915
Authority: WO
Inventors: Kenneth J. Weeks
Original assignee: Duke University
Priority date: 1996-11-05
Filing date: 1997-11-04
Publication date: 1998-05-14

Abstract

Methods and systems produce radio-nuclide by colliding a focused electron beam with a target cartridge (20) containing a target material capable of being radio-activated by the energy of the electron beam. The target material is translated relative to the electron beam along at least two axes. In this regard a target cartridge is provided according to the present invention which includes a tubular shelf (20a) formed either of a material which allows interior passage of the electron beam (e.g., aluminum) or of a material which converts the kinetic energy of the electron beam into electromagnetic energy (e.g., tungsten). The tubular shell defines an interior hollow space which houses the target material to be irradiated, e.g., an intraluminal stent. End caps (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 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 in contact therewith.

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 "nuclear medicine", primarily in the availability and/or accessibility 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 "point-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 "on-site". It is towards fulfilling such a need that the present invention is directed.

The present invention finds particular utility in providing radionuclides on-site that may be employed to solve the problems of: (1 ) restenosis after balloon angioplasty and stent placement for cardiovascular disease; (2) ingrowth of tumor for esophageal and pulmonary stents in cancer therapy; (3) beta emitting plaques for treatment of macular degeneration and prevention of blindness; (4) production of short lived radioisotope particulate emulsions for prostate cancer implant procedures; (5) production of radioactive stents to alleviate the symptoms of benign prostate hyperplasia; (6) production of radiopharmaceuticals for diagnosis and therapy, and (7) intraoperative see implantation for cancer therapy. Broadly, the present invention is directed to methods and systems for producing radionuclides by colliding a focused electron beam with a target cartridge containing a target material capable of being radioactivated by the electromagnetic energy potential of 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 hours or less (e.g., aluminum, tungsten, tantalum and the like).

The tubular shell defines an interior hollow space which houses the target material to be irradiated, e.g. an intraluminal stent. The tubular shell according to the nature of the contained target material either permits entry of the high energy electrons into the interior space or alternatively converts the kinetic energy of the electrons into electromagnetic energy (photons). 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's energy.

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 Clinac™ 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 optionally 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 "relaxing" 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 "packets" 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 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 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 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 A₂ 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 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 at least 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 A₂ 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. 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 A_e. 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 "low atomic number" is meant a material having an atomic number (Z) less than about 30, and more preferably less than about 13. Conversely, the term "high atomic number" is meant a material having an atomic number (Z) of greater than about 30, more preferably grater than about 70, for example between about 70 and about 82. 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 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 either a low atomic number material or a high 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, titanium, tantalum, tungsten, lead and rhenium.

The wall 20a_! of the tubular shell 20 for one application 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 another application, the wall is thick enough to convert electron energy into photon energy and yet thin enough that all photons are not attenuated too much before passage into the interior target containing space. 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 shorter activation times for the target material up to a point and then subsequently result in larger activation times. Thus, a balance between the thickness of wall 20a, and the nature of the target material contained therewithin must be made. By way of the example, when the inside target material is formed of a thick high atomic number metal, the tubular shell 20 is formed from aluminum, in which case 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. When the inside target material is formed of relatively thin samples, the tubular shell 20 is formed from a relatively high atomic number material, such as tantalum or tungsten, in which case the thickness of the wall should not exceed about 5.0 mm, and preferably should be between about 2.0 to about 4.0 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 or tantalum. 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 or tantalum. 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 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 an appropriate wall thickness. 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 its cartridge is 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, lr, C, F, P, Sc, Cu, Zn, Pt, Ga, Ni, Te, Pm, Ho, Ti, Yb, Ta and Au. If the target material is in the form of an intraluminal stent, then nickel (nitinol), 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, Sc, ⁶²Cu, ⁶⁴Cu, ⁶³Zn, ⁶⁸Ga, ⁵⁷Ni, ¹²⁷Te, ¹²⁹Te, ¹⁴⁰Pm, ⁴⁷Sc, ¹⁶⁴Ho, 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 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. In this case, because the target material is thin, replacement of the aluminum cartridge with a tantalum cartridge of some 2.5 mm thickness would decrease the time to produce the same to some 2 minutes.

*************

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 focused on movement of the target cartridge relative to the electron beam, the target cartridge 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). It is well known to those skilled in the art that the production of photons in the target cartridge's tubular shell is enhanced by the use of a high atomic number material. This is the preferred embodiment when the contained target material does not cause the conversion of electron energy into photons, or may be such as to be destroyed by direct high energy electron bombardment. When substantial amounts of target material are included, then the preferred embodiment is to use a thin aluminum shell. Therefore the cartridge design depends on the explicit loading of the cartridge. This art is further explained by the following example. Consider that a 2 kW, 25 MeV electron beam will irradiate a 2.2 gram tantalum target material whose shape is a cylindrical shell having an inner radius of 0.25 mm, an outer radius of 3.25 mm and length of 4 mm. This amount of tantalum is consistent with the requirements of prostrate implants. 600

: Ci of ¹⁸⁰Ta will be produced in 30 minutes if a 1 mm thick target cartridge container is made of aluminum. In this case, substituting tantalum or tungsten material for the target wall does not appreciably change the time required for irradiating the target material. One skilled in the art recognizes that the target material itself is generating photons which enhance the activation.

As an example of how these issues are decided explicitly, the following will describe a method whereby the various proportions may be determined. First, the dose is calculate at various distances from the target material when it is to be utilized, according to all the isotopic emissions expected from the irradiated material (e.g., information obtained from Lederer and Shirley, Table of Isotopes (1988), incorporated fully hereinto by reference). Monte Carlo programs (such as MCNP-4A, Los Alamos National Laboratory, or any other Monte Carlo program which generally tracks the paths of electrons, and photons through a material) are appropriate software tools to calculate the dose(s). A target dose is chose for the therapy at a given position and the former is divided by the latter to ascertain the number of decays (of all the isotopic constituents produced in the target material by the electron bombardment) required to produce such a dose. The target material is encapsulated with its target cartridge (material and thickness) and the Monte Carlo method used to evaluate the flux (number of particles per unit area per unit energy) crossing the target material per electron emitted from the linear accelerator. The thickness of the cartridge is varied to maximize this flux and minimize the energy absorbed by the target material. The flux times the experimental cross section (probability of creating a radioisotope) is integrated for all isotopic parents considered in the first step of this procedure. The result of the integration multiplied by the emission rate of the electrons from the linear accelerator will yield the amount of time required to bombard the target material/target cartridge with electrons to produce a sufficient quantity of radioactive material which will deliver a given target dose. The time required is then evaluated as commercially feasible and the various parameters are adjusted for the most cost- effective solution.

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 cartridge as in claim 1 , wherein said tubular shell is formed from aluminum.

8. A target cartridge as in claim 1 , wherein said tubular shell is formed from tungsten.

9. A target cartridge as in claim 1 , wherein said target material is in the form of a wire or mesh structure.

10. A target cartridge as in claim 1 , wherein said target material is in the form of particulates.

11. A target cartridge as in claim 1 , wherein said tubular shell and end caps are each formed of aluminum.

12. A target cartridge as in claim 1 , wherein said tubular shell and end caps are each formed of tungsten.

13. 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, Ti, Yb, Ta and Au.

14. 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.

15. A method as in claim 14, wherein said beam of electrons has an electron energy between about 10 MeV to about 50 MeV.

16. A method as in claim 14, 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, Ti, Yb, Ta and Au.

17. A method as in claim 14, 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, ¹⁸³Ta, ¹⁸⁹Re, ¹⁹⁴lr, ¹⁹⁵lr, ¹¹C, ¹⁸F, ³⁰P, ⁴⁴Sc, ⁶²Cu, ⁶⁴Cu, ⁶³Zn, ⁶⁸Ga, ⁵⁷Ni, ¹²⁷Te, ¹²⁹Te, ⁴⁷Sc, ¹⁴⁰Pm, ¹⁶⁴Ho, ¹⁷⁵Yb, ¹⁷⁹Lu, ¹⁸⁰Ta, ¹⁸⁴Re, ¹⁸⁶Re, and ¹⁹⁶Au.

18. A method as in claim 14, wherein said target material is linearly translated along two axes which are mutually perpendicular to each other and to the electron beam.

19. A method as in claim 18, wherein said target material is rotated about said perpendicular axis.

20. A method as in claim 14, including cooling said target material.

21. A method as in claim 14, including determining the number of electrons in said beam per unit time.

22. A method as in claim 14, wherein said electrons are directed toward said target material in packets of electrons per unit time.

23. A method as in claim 14, which includes positioning an electron dump downstream of said target material.

24. A method as in claim 23, which includes cooling said electron dump with a cooling medium.

25. 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 cartridge and an enclosed target material 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.

26. A system as in claim 25, wherein said translator assembly includes a support member for supporting said target material for reciprocal linear movements perpendicular to said beam path.

27. A system as in claim 25 or 26, wherein said translator assembly includes an adjustment member for supporting said target material for reciprocal linear movements substantially perpendicular to said beam path.

28. A system as in claim 27, wherein said translator assembly includes a rotatable shaft for supporting and rotating said target material relative to said beam path.

29. A system as in claim 25, further comprising a beam dump positioned downstream of said translator assembly in said beam path.

30. A system as in claim 29, wherein said beam dump includes a forward section for collecting electrons emitted by said electron generator, and a downstream heat-transfer section.

31. A system as in claim 25, further comprising a cooling system for cooling said target material during irradiation by said electron beam.

32. A system as in claim 30, further comprising a cooling system for cooling said target material and said beam dump during irradiation of said target material by said electron beam.

33. A system as in claim 25, further comprising a controller for controlling translational movement of said target material relative to said electron beam.

34. 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 cartridge in the beam path so that said target cartridge is irradiated with said electron beam and for translating said target cartridge relative to said beam path.

35. A system as in claim 34, wherein said target cartridge is formed of a high atomic number material having a predetermined thickness sufficient to convert kinetic energy of the electron beam into electromagnetic energy, thereby enhancing activation of said target material contained therewithin.

36. A system as in claim 35, wherein the target cartridge is formed of tungsten.

37. A system as in claim 34, wherein said target cartridge is formed of a low atomic number material having a predetermined thickness sufficient to allow direct passage of high energy electrons of the beam into said target material contained therewithin.

38. A system as in claim 37, wherein the target cartridge is formed of aluminum.