Systems and methods for producing actinium-225

Abstract

The present disclosure provides systems, methods, and apparatus related to the production of actinium-225. In one aspect, a target is irradiated with a beam of deuterons to generate a beam of neutrons. A radium-226 target is irradiated with a beam of neutrons to generate radium-225.

Description

[Technical field]

[0001] Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 830,687, filed April 8, 2019, which is incorporated herein by reference.

[0002] [Statement of government support] This invention was made with Government support under Contract No. DE-AC02-05CH11231 awarded by the U.S. Department of Energy. The Government has certain rights in this invention.

[0003] The present disclosure relates generally to systems and methods for producing radionuclides using secondary neutrons from deuteron decomposition, and more specifically to systems and methods for producing actinium-225 using secondary neutrons from deuteron decomposition. [Background technology]

[0004] Actinium-225 is a promising radionuclide for use in a new form of cancer treatment called targeted alpha particle therapy. Actinium-225 has a relatively long half-life (i.e., about 10 days) followed by a short sequence of four alpha decays that can generate the type of double-stranded DNA damage required to detect tumor growth. It does not produce long-lived radioactive products in its decay. The relatively long half-life allows for its incorporation into target biomolecules.

[0005] Actinium-225 has already shown promise for use in the treatment of advanced metastatic prostate cancer. For example, in clinical trials, actinium-225 has been attached to PSMA-617 (prostate membrane specific antigen 617), a small molecule designed to bind to a protein found at high levels in the majority of prostate cancers. With it attached to the cancer cells, actinium-225 emits a highly targeted dose of radiation that can kill the cancer cells while minimizing damage to the surrounding healthy tissue, and has been shown to have remarkable results in patient survival.

[0006] There is currently insufficient actinium-225 available to allow for large-scale clinical studies. This isotope is currently produced in very limited quantities from the decay of uranium-233, produced at Oak Ridge National Laboratory as part of the U.S. nuclear weapons program. The long half-life of uranium-233 (i.e., 159,000 years) makes the rate of production of actinium-225 very slow. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent Application Serial No. 16 / 329,178 [Patent Document 2] U.S. Patent Application Serial No. 16 / 365,132 [Patent Document 3] U.S. Patent Application Serial No. 16 / 336,665 Summary of the Invention [Problem to be solved by the invention]

[0008] One method for producing actinium-225 is 232 One approach is to use high energy (e.g., 100 MeV to 200 MeV and higher) proton-induced spallation of Th. However, this method is not feasible as it can destroy some of the long-lived lanthanide fission products, as well as 227 This leads to the co-generation of Ac. 227Ac has a life span of 21.772 years, making it an unwanted contaminant. Many physicians do not want to expose young cancer patients to doses of actinium-225 that contain any actinium-227 because of the potential long-term risks that may be associated with even trace amounts of actinium-227 (e.g., less than about 0.5 percent of the total actinium).

[0009] The second method is 226 Ra(p,2n) 225 A possible solution is to use the radium-Ac reaction. However, this reaction is also difficult because the reactivity of radium requires the use of irregular salt targets with limited thickness. It is believed that heating of the target from the proton beam could present a potential contamination hazard. [Means for solving the problem]

[0010] Actinium-225 is part of a promising class of radiopharmaceuticals. Described herein are methods for producing the radionuclide actinium-225 that are efficient and do not co-produce dangerous radioactive impurities that would prevent its use in patients. These methods involve irradiating the naturally occurring isotope radium-226 with an energetic neutron beam from a thick target deuteron dissociation to form radium-225. The radium-225 then decays to actinium-225, which is then chemically separated from the radium-226 for use in producing radiopharmaceuticals.

[0011] The details of one or more embodiments of the subject matter described herein are set forth in the accompanying drawings and the description below. Other features, aspects, and advantages will become apparent from the description, drawings, and claims. It should be noted that the relative dimensions of the following figures may not be drawn to scale. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 shows an example of a flow chart illustrating a process for producing actinium-225. [Diagram 2] FIG. 1 shows an example schematic of a setup for carrying out the methods described herein. [Diagram 3] FIG. 1 shows an example of a flow diagram illustrating a process for producing a radionuclide. [Figure 4] FIG. 1 shows an example schematic of a setup for carrying out the methods described herein. [Diagram 5] FIG. 1 shows an example schematic of a fixture used to perform the methods described herein using the Lawrence Berkeley National Laboratory (LBNL) 88 inch cyclotron. [Figure 6] FIG. 1 shows an example graph of a neutron emission spectrum generated by an 88-inch cyclotron for 50 MeV deuterons. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Reference will now be made in detail to certain specific examples of the invention, including the best mode contemplated by the inventors for carrying out the invention. Examples of these specific embodiments are illustrated in the accompanying drawings. While the invention will be described in conjunction with these specific embodiments, it will be understood that it is not intended to limit the invention to the described embodiments. On the contrary, it is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.

[0014] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. Certain exemplary embodiments of the present invention may be practiced without some or all of these specific details. In other instances, well-known process operations are not described in detail in order to not unnecessarily obscure the present invention.

[0015] Various techniques and features of the invention will sometimes be described in the singular for clarity. It should be noted, however, that some embodiments include multiple iterations of a technique or multiple instantiations of a feature unless otherwise noted.

[0016] The terms "about" or "approximately" and the like are synonymous and are used to indicate that the value modified by this term has an understood range associated with it, which may be ±20%, ±15%, ±10%, ±5%, or ±1%. The term "substantially" and the like are used to indicate that a value is close to a target value, which may mean, for example, that the value is within 80% of the target value, within 85% of the target value, within 90% of the target value, within 95% of the target value, or within 99% of the target value.

[0017] The radiochemical or radiological purity of actinium-225 produced using the fragmentation method (described above) will never exceed about 99.9%. At this purity level, there is approximately equal radiation dosage from actinium-225 and actinium-227. It is believed that radiation dosage from actinium-227 may lead to additional cancers.

[0018] Described herein are methods for producing actinium-225 that is free of contamination from both fission debris and actinium-227. The fast neutron methods described herein produce actinium-225 with 99.9999% radiochemical purity (i.e., three orders of magnitude better than fragmentation methods). This radiochemical purity of actinium-225 can be further improved (i.e., at least with respect to actinium-227 contaminants) using chemical separation. It is believed that these production methods can be used by pharmaceutical companies to produce 225-actinium doped prostate specific membrane antigen-617 (PSMA-617) for use in cancer therapy.

[0019] Most medical radionuclides are currently produced using charged particle or low energy neutron beams. The method described herein produces radioisotopes using secondary neutrons from thick target deuteron disintegration. Deuterons can be accelerated using charged particle accelerators such as, for example, cyclotrons, Van de Graaff accelerators, pelletrons, radio frequency quadrupole (RFQ) linear accelerators (linacs), tandem linacs, or synchrotrons. Producing neutrons in this manner using charged particle accelerators allows for focusing most, most, or all of the neutrons in the same direction at a target (e.g., a radium target), which is an advantage over reactor-based production techniques. Also, about 95 percent of the neutrons generated pass through the target, and therefore the possibility exists to use these neutrons to bombard a secondary target.

[0020] 225 The disclosed method for producing Ac is 226 Ra(n,2n) 225 Ra reaction and subsequent 225 Into Ac 225 β decay of Ra (t 1 / 2 = 14.9 ± 0.2 days). This method uses a (Z 2 / A), which results in limited fission cross sections and correspondingly higher (n,2n) cross sections for neutron energies up to 20 MeV.

[0021] In some embodiments, a method of producing actinium-225 includes irradiating a target with a beam of deuterons to generate a beam of neutrons, irradiating a radium-226 target with a beam of neutrons to generate radium-225, allowing at least a portion of the radium-225 to naturally decay into actinium-225 over a period of time, and separating the actinium-225 from unreacted radium-226 and radium-225.

[0022] FIG. 1 shows an example of a flow diagram illustrating a process for producing actinium-225. Beginning at block 102 of the method 100 shown in FIG. 1, a target is irradiated with a beam of deuterons to generate a beam of neutrons. In some embodiments, the beam of deuterons is about 1 centimeter (cm) to about 5 cm in diameter, about 1 cm to 1.5 cm in diameter, or about 1.5 cm in diameter. In some embodiments, the target comprises a beryllium target. In some embodiments, the beryllium target is about 2 millimeters (mm) to 8 mm thick, or about 3 mm thick. Some advantages of using a beryllium target include that beryllium is a relatively inexpensive material, beryllium has good mechanical and thermal properties, beryllium is not radiologically activated with deuteron irradiation, and high yield of neutrons out per deuteron in with deuteron irradiation. In some embodiments, the target is selected from the group consisting of a beryllium target, a carbon target, a tantalum target, and a gold target.

[0023] In some embodiments, the target is positioned near the radium-226 target. In some embodiments, the target is positioned about 0.5 millimeters to 1 millimeter from the radium-226 target. In some embodiments, the target is positioned about 0.5 millimeters to 10 millimeters from the radium-226 target. In some embodiments, the target is positioned about 10 millimeters from the radium-226 target. In some embodiments, the target and the radium-226 target are not in contact.

[0024] In some embodiments, the target is held in a water-cooled fixture. When the target is irradiated with deuterons, power (e.g., about 100 watts to 300 watts) is deposited on the target. This power causes the target to heat up. The water-cooled fixture can cool the target.

[0025] In some embodiments, the deuterons in the beam of deuterons have an energy of about 25 megaelectron volts (MeV) to 55 MeV, or about 33 MeV. In some embodiments, the beam of deuterons is generated using a charged particle accelerator (e.g., a cyclotron). In some embodiments, the beam of neutrons is generated using a charged particle accelerator (e.g., a cyclotron). In some embodiments, the beam of neutrons is generated using a charged particle accelerator (e.g., a cyclotron). ∧ 10 neutrons / cm2 / sec to 3×10 ∧ It has a fluence of 12 neutrons / cm2 / sec. In some embodiments, the neutrons in the beam of neutrons have an energy of about 10 MeV or higher.

[0026] In some embodiments, a beam of about 10 micro-A to 1 milli-A of deuterons having an energy of about 33 MeV irradiates a beryllium target. ∧ 10 neutrons / cm2 / sec to 1×10 ∧ It produces a neutron beam with a flux of 12 neutrons / cm2 / sec. The flux of the neutron beam depends on the incident energy and intensity of the deuteron beam. In general, the higher the incident energy of the deuteron beam, the higher the flux of the neutron beam. The average energy of the neutrons in the neutron beam is about half the energy of the deuteron beam, or about 17 MeV.

[0027] In some embodiments, a beam of about 10 micro-A to 1 milli-A of deuterons having an energy of about 50 MeV irradiates a beryllium target. This is about 33 MeV deuterons or about 3×10 ∧ 10 neutrons / cm2 / sec to 3×10 ∧ It produces a beam of neutrons that is about three times as intense as the beam of neutrons produced using 12 neutrons / cm2 / sec. The average energy of the neutron beam is about half the energy of the deuteron beam, or about 25 MeV.

[0028] In some embodiments, the neutrons are not thermal neutrons generated in a nuclear reactor. In some embodiments, the neutrons are not generated by a spallation source. Thermal neutrons are generally considered to be neutrons having energies less than about 10 kiloelectron volts (keV). Thermal neutrons have an average energy of about 25 millielectron volts (meV). A large percentage (e.g., about 95% to 99%) of the neutrons generated using a cyclotron in the methods described herein are considered to be fast neutrons or neutrons having energies of about 1 MeV and higher.

[0029] In some embodiments, the initial diameter of the beam of neutrons (i.e., the diameter of the neutron beam being emitted from the target) is approximately the diameter of the beam of deuterons, or about 1 cm to 5 cm in diameter, about 1 cm to 1.5 cm in diameter, or about 1.5 cm in diameter.

[0030] The beam of neutrons is considered to be a forward focused beam of neutrons and is not neutrons being isotopically emitted from the source. Figure 5 shows an example of a graph of the percentage of neutrons in the neutron beam versus emission angle. 0 degrees is neutrons that are emitted in the same direction as the deuterons in the deuteron beam. As can be seen in Figure 6, approximately 90% of the neutrons generated are focused (e.g., directionally focused) in a direction approximately parallel to the deuteron beam.

[0031] Returning to FIG. 1 , in block 104, the radium-226 target is irradiated with a beam of neutrons to generate radium-225. Radium-226 is a radioactive isotope of radium. In some embodiments, the radium-226 target reacts via a (n,2n) reaction to form radium-225. In some embodiments, the radium-226 target is not positioned in a nuclear reactor. In some embodiments, the radium-226 target is irradiated with the beam of neutrons for a period of at least one day. In some embodiments, the radium-226 target is about 1 mm to 10 mm thick.

[0032] In some embodiments, the radium-226 target comprises a radium-226 salt. The radium-226 salt comprises radium nitrate (Ra(NO3)2). In some embodiments, the radium-226 salt target has a mass of about 1 milligram (mg). For larger scale production of actinium-225, the radium-226 salt target can have a mass of about 100 mg to 1 gram (g) or about 100 mg to 10 g.

[0033] Irradiating a radium-226 target with a beam of neutrons may generate radium-227, which undergoes beta decay to actinium-227. In the experiments described in the Examples below, no generation of actinium-227 has been observed resulting from irradiating radium-226 with a beam of neutrons. In some embodiments, irradiating a radium-226 target with a beam of neutrons does not generate any actinium-227 or any species that decays to actinium-227.

[0034] In block 106, at least a portion of the radium-225 naturally decays to actinium-225 over a period of time. In some embodiments, the radium-225 decays to actinium-225 by beta decay. In some embodiments, the generation of actinium-225 by beta decay of radium-225 avoids the generation of actinium-227 and provides high purity of the generated actinium-225. In some embodiments, the period is at least about 30 days or about 30 days. In some embodiments, the period is at least about 15 days or about 15 days.

[0035] In some embodiments, chemical processing is used to separate actinium from radium when actinium-227 is present or can be present in the radium-226 target for about 1 to 5 hours or about 2 hours after the radium-226 target is irradiated with neutrons. This actinium is disposed of since it will contain most or all of the actinium-227 produced from beta decay as a result of the irradiation. All subsequent actinium collected from this irradiation following this chemical separation will be actinium-225 since radium-225 has a much longer half-life than radium-227. As a result, most of the actinium-225 will still be available for separation without actinium-227 contaminants. At least a portion of the radium-225 then decays to actinium-225 over a period of time.

[0036] Returning to Figure 1, in block 108, actinium-225 is separated from unreacted radium-226 and radium-225. In some embodiments, actinium-225 is separated from unreacted radium-226 and radium-225 using a chemical separation process. In some embodiments, after actinium-225 is separated from unreacted radium-226 and radium-225, actinium-225 does not contain any actinium-227. In some embodiments, after actinium-225 is separated from unreacted radium-226 and radium-225, actinium-225 consists essentially of actinium-225. Further details regarding methods for separation of actinium-225 from radium-226 and radium-225 can be found in U.S. patent application Ser. No. 16 / 329,178, filed Feb. 27, 2019, U.S. patent application Ser. No. 16 / 365,132, filed Mar. 26, 2019, and U.S. patent application Ser. No. 16 / 336,665, filed Mar. 26, 2019, all of which are incorporated herein by reference.

[0037] In some embodiments, prior to irradiating the radium-226 target with the beam of neutrons, the radium-226 target is cleaned to remove any radium-228 and any thorium-228 from the radium-226 target. This cleaning can be performed using a chemical process. Removing the radium-228 and thorium-228 from the target prevents actinium-228 from forming and keeps actinium-228 out of the range of the generated actinium-225.

[0038] Figure 2 shows an example schematic of a setup for carrying out the methods described herein. As shown in Figure 2, a charged particle accelerator 205 generates a beam of deuterons 210. The beam of deuterons 210 irradiates or impinges on a deuteron target 215 (e.g., a beryllium target) to generate a beam of neutrons 220. The beam of neutrons 220 has an angle 225 spread of about 5 degrees. About 90% of the neutrons generated from the deuteron target 215 are within a cone having a spread of about 5 degrees. The beam of neutrons 220 irradiates a radium-226 target 230.

[0039] In some embodiments, the beam of deuterons is passed through an iridium or strontium target prior to irradiating the beryllium target with the beam of deuterons. In some embodiments, the iridium or strontium target is less than about 1 millimeter thick. Passing the deuterons through an iridium-193 target produces the platinum-193m radioisotope by (d,2n reaction). Passing the deuterons through a strontium-86 target produces the yttrium-86 radioisotope by (d,2n reaction).

[0040] Irradiating other targets with secondary neutrons from deuteron decomposition can be used to produce other radioisotopes. For example, a zinc target (i.e., zinc-64 and zinc-67) irradiated with neutrons is believed to produce copper-64 and copper-67. Other radioisotopes that could be produced include astatine-211, bismuth-213, gallium-68, thorium-229, and lead-212. Additional radioisotopes that could be produced are listed below in Table 1, including the isotope that will be irradiated and the reaction that forms the radioisotope.

[0041] TIFF0007616667000001.tif92143

[0042] An example flow diagram illustrating a process for producing radionuclides is shown in Figure 3. In block 302 of the method 300 shown in Figure 3, a target is irradiated with a beam of deuterons to generate a beam of neutrons. In block 304, a target selected from the group of targets consisting of a radium-226 target, a zinc target, a molybdenum target, a phosphorus target, a hafnium target, a titanium target, and a tantalum target is irradiated with the beam of neutrons.

[0043] FIG. 4 shows an example schematic of a setup for carrying out the methods described herein. As shown in FIG. 4, a charged particle accelerator 405 generates a beam of deuterons 410. The beam of deuterons 410 irradiates or impinges on a first target 417 before irradiating or impinging a deuteron target 415 (e.g., a target or beryllium) to generate a beam of neutrons 420. In some embodiments, the first target 417 includes iridium-193 or strontium-86. In some embodiments, the first target 417 is about 25 microns to 500 microns thick. The beam of neutrons 420 irradiates multiple targets. Shown in FIG. 4 are a second target 430, a third target 435, and a fourth target 440. It is contemplated that more targets may be included. In some embodiments, targets 430, 435, and 440 are each about 0.1 mm to 0.5 mm thick or about 0.1 mm to mm thick.

[0044] Neutrons pass through a single target without losing much energy, and most of the neutrons in a beam of neutrons do not interact with a single target. The majority of neutrons pass through most materials without interaction. For targets on which the neutrons impinge, it is contemplated that very thick targets could be used (e.g., up to about 10 cm thick), multiple target materials as shown in FIG. 4 (e.g., up to about 10 cm thick depending on the density of the target material) could be used, or combinations thereof.

[0045] The following examples are intended to be illustrative of the embodiments disclosed herein, and are not intended to be limiting.

[0046] Working Example In the embodiment described herein, an 88 inch cyclotron at Lawrence Berkeley National Laboratory (LBNL) was used to generate a beam with deuterons. Deuterium is one of the two stable isotopes of hydrogen. The nucleus of deuterium, called a deuteron, contains one proton and one neutron.

[0047] The 88-inch Cyclotron ("88") at LBNL is a variable-energy, high-current, multi-particle cyclotron capable of accelerating ions ranging from protons to uranium with energies approaching and exceeding the Coulomb Barrier. Maximum currents on the order of 10 particles·μA with a beam power limit of 1.5 kW can be extracted from the machine for use in experiments in seven experimental "caves". Focused light ion beams, including deuterons, can be used in both the cyclotron vault and Cave 0.

[0048] FIG. 5 shows an example schematic of a fixture used to perform the methods described herein using the 88 inch cyclotron at LBNL. As shown in FIG. 5, fixture 500 holds a beryllium target 510 and a target 520 (e.g., a radium-226 target). A beam of deuterons accelerated by the cyclotron irradiates beryllium target 510. This generates a beam of neutrons (i.e., a beam of secondary neutrons) that irradiate target 520.

[0049] Figure 6 shows an example graph of the neutron emission spectrum produced by an 88-inch cyclotron for 50 MeV deuterons. The points in the graph are data and the solid line is the theoretical prediction.

[0050] The following method was used to produce actinium-225: First, a highly focused beam of energetic secondary neutrons was produced by accelerating a deuterium ion beam onto a thick beryllium target. A deuteron beam was produced using the LBNL 88 inch cyclotron.

[0051] Second, this beam of secondary neutrons was incident on a sample of radium-226, which has a half-life of 1600 years and is found naturally in uranium ore. This resulted in the production of radium-225, which has a half-life of 14.9 days. This irradiation period would typically take place over one or more days. Because neutrons have an extremely long range in matter compared to protons, the radium-226 target could be very thick, resulting in a high production rate of radium-225.

[0052] Third, over a period of tens of days, a portion of the radium-225 decayed into actinium-225.

[0053] Fourth, actinium-225 has been separated from radium-226 for use in medical applications, with the unreacted radium-226 being returned for use in subsequent irradiation using secondary neutrons.

[0054] The production rate of actinium-225 when irradiating a beryllium target with 33 MeV deuterons is about 2.1 mCi per milliampere-hour (2.1 mCi / mAh / g) of deuteron beam per gram of radium-226. For a 0.1 mA beam of deuterons, the production rate of actinium is about 0.21 mCi / hour / gram or about 5.04 mCi / day / gram.

[0055] Below is a table with the experimental parameters and results of two separate runs of an 88 inch cyclotron to generate Actinium-225.

[0056] TIFF0007616667000002.tif115162

[0057] The numbers for DGA Actinium-225 / AG50 Actinium-225 are the activities recovered after chemical separation, and the numbers for DGA Radium / AG50 Radium are the activities of the contaminating Radium-226. The Radium-226 was presumably attenuated by the additional chemical separation steps. For example, each separation reduces the Actinium-225 / Radium-226 ratio by approximately 10. ∧ 4, while each separation only reduces the actinium-225 concentration by about 10%.

[0058] It should be noted that less actinium-225 was produced / recovered in Run 2 than in Run 1. Even when considering the differences in neutron fluence, deuteron beam current, radium-226 cross section, initial mass of radium-226, and production / decay conditions, there was still about a 30% lower production rate in Run 2 than in Run 1. This could be due to the beam spot alignment / focus of the deuteron beam, since the deuteron dissociation reaction is extremely forward-focused. However, simulations have not yet been performed to confirm this discrepancy.

[0059] conclusion In the foregoing specification, the invention has been described with reference to specific embodiments. However, those skilled in the art will recognize that various modifications and changes can be made without departing from the scope of the invention as set forth in the following claims. Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of the invention. [Explanation of symbols]

[0060] 100 The method of the present invention 102 Block for irradiating targets with a deuteron beam 104 Block for irradiating a radium-226 target with a beam of neutrons 106 A block that allows radium-225 to decay naturally into actinium-225 over a period of time. 108 Block for separating actinium-225 from unreacted radium-226

Claims

1. irradiating the target with a beam of deuterons to produce a beam of neutrons; irradiating a radium-226 target with said beam of neutrons to generate radium-225, and after irradiating said radium-226 target, irradiating one or more additional radionuclide targets with said beam of neutrons; allowing at least a portion of the radium-225 to decay naturally into actinium-225 over a period of time; and separating said actinium-225 from unreacted radium-226 and said radium-225 for use in the production of medical radionuclides; The method according to claim 1, further comprising:

2. 2. The method of claim 1, wherein the radium-226 reacts to form the radium-225 via an (n,2n) reaction.

3. 2. The method of claim 1, wherein the radium-225 decays to the actinium-225 by beta decay.

4. 2. The method of claim 1, wherein the period is 15 days.

5. 2. The method of claim 1, wherein after the separating step, the actinium-225 is free of any actinium-227.

6. 2. The method of claim 1, wherein the step of irradiating the radium-226 target occurs for a period of at least one day.

7. 2. The method of claim 1, wherein the target is positioned 0.5 to 10 millimeters from the radium-226 target.

8. 2. The method of claim 1, wherein the target and the radium-226 target are not in contact.

9. the target comprises a beryllium target; the beryllium target is 2 millimeters to 8 millimeters thick; 2. The method of claim 1 .

10. 2. The method of claim 1, wherein the radium-226 target is 1 millimeter to 10 millimeters thick.

11. 2. The method of claim 1, wherein the deuterons in the beam of deuterons have an energy between 25 MeV and 55 MeV.

12. 2. The method of claim 1, wherein the step of irradiating the radium-226 target with the beam of neutrons does not generate any actinium-227 or any species that decay to actinium-227.

13. 2. The method of claim 1 , wherein the beam of deuterons is generated using a cyclotron.

14. The neutron beam is 1×10 10 Neutrons / cm 2 / sec to 3 x 10 12 Neutrons / cm 2 2. The method of claim 1, having a flux of 1000 .mu.m / sec.

15. 2. The method of claim 1, wherein the neutrons in the beam of neutrons have an energy of 10 MeV or greater.

16. 2. The method of claim 1, wherein the radium-226 target is not positioned in a nuclear reactor.

17. 2. The method of claim 1, wherein the neutrons are not thermal neutrons produced in a nuclear reactor.

18. irradiating a target with a beam of deuterons to generate a beam of neutrons, the beam of neutrons being greater than 1×10 10 Neutrons / cm 2 / sec to 3 x 10 12 Neutrons / cm 2 / sec, and the neutrons in the beam of neutrons have an energy of 10 MeV or higher; irradiating a radium-226 target with said beam of neutrons to generate radium-225, and after irradiating said radium-226 target, irradiating one or more additional radionuclide targets with said beam of neutrons; allowing at least a portion of the radium-225 to decay naturally into actinium-225 over a period of time; and separating said actinium-225 from unreacted radium-226 and said radium-225 for use in the production of medical radionuclides; The method according to claim 1, further comprising:

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