Polymer coatings for brachytherapy devices

Abstract

To provide brachytherapy for, e.g., the treatment of cancerous tumors.SOLUTION: Described embodiments relate to an apparatus (20, 21), which includes a support (22), including an outer surface (24) and configured for insertion into a body of a subject. The apparatus further includes: multiple atoms (26) of a radionuclide, which radioactively decays to produce a daughter radionuclide, coupled to the outer surface; and a layer (28, 33) of a polymer, permeable to the daughter radionuclide, that covers the atoms. Other embodiments are also described.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to the field of brachytherapy, such as for the treatment of cancerous tumors. [Background technology]

[0002] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 62 / 504,800, entitled “PRODUCTION OF RADIATION SOURCES,” filed May 11, 2017, the disclosure of which is incorporated herein by reference.

[0003] Brachytherapy involves placing a radiation source inside a subject's body so that the source emits radiation inside the body that can kill cancer cells that are near the source.

[0004] Arazi, Lior et al., "Treatment of Solid Tumors by Interstitial Release of Short-Lived Recoiling Alpha Emitters," Physics in Medicine & Biology 52.16 (2007):5025, incorporated herein by reference, describes a method of utilizing alpha particles to treat solid tumors. The tumor is treated with an interstitial radiation source that continuously releases short-lived alpha-emitting atoms from its surface. The atoms disperse within the tumor, delivering a high dose through alpha decay. The scheme is implemented using a thin wire radiation source impregnated with Ra-224, which releases Rn-220, Po-216, and Pb-212 atoms upon recoil.

[0005] No. 8,894,969 to Kelson et al., the disclosure of which is incorporated herein by reference, describes a radiation therapy method that involves placing a predetermined amount of a radionuclide selected from the group consisting of radium-223, radium-224, radon-219, and radon-220 near and / or within a tumor of a subject for a predetermined period of time. The predetermined amount and predetermined period of time are sufficient to administer to the tumor a predetermined therapeutic dose of decay chain nuclide and alpha particles for that radionuclide. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Provisional Patent Application 62 / 504,800 [Patent Document 2] U.S. Patent No. 8,894,969 [Non-patent literature]

[0007] [Non-Patent Document 1] Arazi, Lior et al., "Treatment of solid tumors by intratissue delivery of short-lived recoiling alpha emitters," Physics in Medicine & Biology 52.16 (2007): 5025 Summary of the Invention

[0008] According to an embodiment of the present invention, there is provided a device having a support having an outer surface and configured for insertion into a subject's body, the device further having a plurality of atoms of a radionuclide bound to the outer surface and radioactively decaying to produce a daughter radionuclide, and a layer of polymer covering the atoms, the layer being permeable to the daughter radionuclide.

[0009] In some embodiments, the atoms are disposed on an exterior surface. In some embodiments, the support is in the shape of a cylinder. In some embodiments the radionuclide is an alpha emitting radionuclide. In some embodiments, the radionuclide has one isotope of radium selected from the group of isotopes consisting of Ra-224 and Ra-223. In some embodiments, the daughter radionuclide is an alpha-emitting daughter radionuclide.

[0010] In some embodiments, the layer is 0.1-2 microns thick. In some embodiments, the thickness is 0.1-1 microns. In some embodiments, the diffusion coefficient of the daughter radionuclide in the polymer is at least 10 -11 cm 2 / second. In some embodiments, the polymer is selected from the group of polymers consisting of polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and polysulfone.

[0011] In some embodiments, The layer is an outer layer, the polymer is a first polymer; The device further comprises a second polymeric inner layer, which is permeable to the daughter radionuclide and which coats the outer surface, the atoms being bonded to the outer surface by bonding to the inner layer. In some embodiments, the inner layer is 0.1-2 microns thick. In some embodiments, the inner layer is 0.1-1 microns thick.

[0012] According to further embodiments of the present invention, there is provided a method comprising the steps of: binding a plurality of atoms of a radionuclide that radioactively decays to produce a daughter radionuclide to an outer surface of a support configured for insertion into a subject's body; and after binding the atoms to the outer surface, covering the atoms with a layer of polymer that is permeable to the daughter radionuclide. In some embodiments, coating the atoms comprises withdrawing the support from a solution of polymer, whereby a layer of polymer coats the outer surface, thereby coating the atoms.

[0013] In some embodiments, The layer is an outer layer, the polymer is a first polymer; The method further includes coating the exterior surface with an inner layer of a second polymer prior to the step of bonding the atoms to the exterior surface; and Bonding the atoms to the outer surface includes bonding the atoms to the outer surface by bonding the atoms to an inner layer.

[0014] According to an embodiment of the present invention, there is provided a method further comprising inserting a radiation source into a subject's body. The radiation source has a support having an outer surface, a plurality of atoms of a radionuclide that radioactively decay to produce a daughter nuclide bound to the outer surface, and a layer of polymer that is transparent to the daughter radionuclide and covers the atoms. The method further comprises leaving the radiation source in the subject's body such that nuclei of the daughter radionuclide diffuse through the layer of polymer. In some embodiments, inserting the radiation source into the subject's body comprises inserting the radiation source into a tumor within the subject's body. In some embodiments, inserting the radiation source into the subject's body comprises inserting the radiation source such that the radiation source is within 0.1 mm of a tumor in the subject's body. The present invention will be more fully understood from the following detailed description taken in conjunction with the drawings in which: [Brief description of the drawings]

[0015] [Figure 1] FIG. 1 is a schematic diagram of a brachytherapy device according to some embodiments of the present invention. [Diagram 2] FIG. 1 is a schematic diagram of a brachytherapy device according to some embodiments of the present invention. [Diagram 3]FIG. 1 is a schematic diagram of a dip coating technique for manufacturing a brachytherapy device, according to some embodiments of the present invention. [Figure 4] FIG. 1 is a flow diagram of a method for manufacturing a brachytherapy device according to some embodiments of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] (overview) In an embodiment of the invention, atoms of an alpha-emitting radionuclide, such as radium-224 (Ra-224), are deposited on the surface of a support, such as a wire. The support, which in addition to having the radionuclide deposited thereon, is referred to as a "radiation source" or simply a "source", is then inserted into a solid tumor in the subject's body. The radionuclide then undergoes a chain of radioactive decays, and alpha particles that kill the cancer cells of the tumor are emitted from the radionuclide atom and successive decay chain nuclei. (Each of these nuclei is referred to herein as a "daughter nucleus" of the preceding nucleus in the chain. In general, the terms "atom" and "nucleus" may be used interchangeably herein.) Advantageously, the decay chain nuclei travel through the tumor by diffusion and / or convection. This allows alpha particles to be emitted even at relatively large distances from the radiation source.

[0017] A challenge in applying the above brachytherapy techniques is that the radionuclides generally need to be covered to prevent them from being washed away from the source by bodily fluids before they have a chance to decay, but covering the radionuclides may inhibit the detachment of the daughter nuclei from the source. One option, described in the aforementioned U.S. Patent No. 8,894,969 to Kelson, is to cover the radionuclides with a very thin cover, e.g., 5-10 nanometers thick, that the daughter nuclei may penetrate as they recoil from the source. However, such covers may be difficult to manufacture.

[0018] To address this challenge, embodiments described herein provide a thicker polymer layer (e.g., having a thickness of 0.1-1 microns) that covers the radionuclide while allowing the daughter nuclei to diffuse out. Such a layer may be applied to the source by immersing the source in a suitable polymer solution such that the source is coated with the polymer. Examples of suitable polymers include polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and polysulfone.

[0019] In some embodiments, prior to the deposition of the radionuclide, a further polymer layer (e.g., having a thickness of 0.1-1 microns) is applied to the surface of the support. The advantage of such an embodiment is that if the daughter nuclei of the radionuclide bounce towards the surface of the support, the daughter nuclei do not adhere to the surface or below the surface. Rather, the daughter nuclei can diffuse outward through the inner polymer layer and then continue to diffuse outward through the outer polymer layer. Typically, the inner polymer layer is applied to the support by immersing the support in a suitable polymer solution. Any of the polymers listed above can be used for the inner layer, provided that they do not dissolve in the solution used to coat the subsequent outer polymer layer.

[0020] (Description of the device) Reference is initially made to FIG. 1, which is a schematic diagram of a brachytherapy device 20 according to some embodiments of the present invention.

[0021] The brachytherapy device 20 includes a support 22 configured for partial or complete insertion into the subject's body. The support 22 may comprise, for example, a needle, a wire, a rod, an endoscope tip, a laparoscope tip, or any other suitable probe. Typically, the support 22 is cylindrical. For example, the support 22 may comprise a cylindrical wire, needle, or rod having a diameter of 0.3-1 mm and / or a length of 5-60 mm. The support 22 includes an outer surface 24.

[0022] The brachytherapy device 20 further includes a plurality of atoms 26 of a radionuclide that decay to produce daughter radionuclides that are attached to the exterior surface 24. For example, each atom 26 of the radionuclide may be located on or slightly below the exterior surface 24. The density of atoms 26 on the exterior surface 24 may be greater than 10 per square centimeter. 11 From 10 14 Between atoms.

[0023] Typically, the radionuclides, daughter radionuclides, and / or subsequent nuclides in the decay chain are alpha-emitting, emitting alpha particles upon the decay of any given nucleus. For example, radionuclides include isotopes of radium (e.g., Ra-224 or Ra-223) that decay by alpha radiation to produce daughter isotopes of radon (e.g., Rn-220 or Rn-219), which decay by alpha radiation to produce isotopes of polonium (e.g., Po-216 or Po-215), which also decay by alpha radiation to produce isotopes of lead (e.g., Pb-212 or Pb-211).

[0024] Typically, atoms 26 are produced by the decay of the preceding radionuclide in the decay chain. For example, atoms of Ra-224 can be produced by spreading a thin layer of acid containing uranium-232 (U-232) over the metal, as described in U.S. Patent No. 8,894,969 to Kelson et al. The U-232 decays to produce thorium-228 (Th-228), which then decays to produce Ra-224.

[0025] The atoms 26 can be attached to the support 22 using any one or more suitable techniques described in the aforementioned U.S. Patent No. 8,894,969 to Kelson et al. For example, a source that generates a flux of radionuclides can be placed in a vacuum near the support 22, such that nuclei recoiling from the source cross the vacuum gap and are collected on or embedded within the outer surface 24. Alternatively, the radionuclides can be electrostatically collected on the support 22 by applying a suitable negative voltage between the source and the support. In such an embodiment, the support 22 can include a conductive metal such as titanium to facilitate electrostatic collection of the radionuclides. For example, the support 22 can include a conductive metal wire, needle, rod, or probe. Alternatively, the support 22 can include a non-metallic needle, rod, or probe coated with a conductive metal coating that includes the outer surface 24.

[0026] The brachytherapy device 20 further includes a layer 28 of a polymer, such as polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and / or polysulfone, that coats the outer surface 24, thus enveloping the atoms 26. The polymer is permeable to the daughter radionuclide, so that the daughter radionuclide may diffuse through the polymer layer 28. For example, the diffusion coefficient of the daughter radionuclide in the polymer is at least 10 -11 cm 2 / sec. Typically, the thickness T0 of polymer layer 28 is 0.1-2 microns, e.g., 0.1-1 microns, such that polymer layer 28 is thick enough to prevent the radionuclides from being washed away, but thin enough to allow diffusion of the daughter radionuclides therethrough. (For ease of illustration, atoms 26 are drawn disproportionately large in relation to the thickness of layer 28.)

[0027] To treat a subject, at least one device 20 is inserted completely or partially into the subject's body, typically at or directly adjacent to the tumor to be treated (e.g., within 0.1 mm, 0.05 mm, or 0.001 mm, etc.). Thereafter, while the device is in the body, the radioactive nuclei decay and emit alpha particles into the tumor. Typically, about 50% of the resulting daughter nuclei recoil inward and attach to the outer surface 24. However, other daughter nuclei recoil outward and enter the polymer layer 28. The diffusivity of these daughter nuclei and / or subsequent nuclei in the decay chain within the polymer layer 28 allows at least a portion of these nuclei (e.g., 99% or more) to diffuse through the polymer layer, break away from the device, and enter the tumor. Thus, for example, the daughter nuclei or other progeny nuclei may diffuse at a rate of 10 per square centimeter per second. 2 10 from atoms 5 Atoms, e.g. 10 3 10 from atoms 4 The alpha particles can enter the tumor at atomic fractions. These nuclides pass through the tumor by diffusion and / or convection and undergo further decay during passage through the tumor. Thus, alpha particles can be emitted at considerable distances from the radiation source.

[0028] In some embodiments, following radioactive decay of at least some of the radionuclide atoms - e.g., after a predetermined period of time and / or in response to monitoring the size of the tumor and / or the rate of emitted alpha particles - the device is removed from the subject. In other embodiments, the device is not removed from the subject.

[0029] Reference is now made to FIG. 2, which is a schematic diagram of an alternative brachytherapy device 21, according to some embodiments of the present invention.

[0030] Device 21 differs from device 20 in that it includes two polymer layers. Device 21 has an inner layer 30 of a first polymer coating outer surface 24 and an outer layer 33 of a second (different) polymer coating inner layer 30. Atoms 26 are bonded to outer surface 24 by being bonded to inner layer 30. For example, each atom 26 is disposed on or slightly below the outer surface of inner layer 30 such that the atom is covered by outer layer 33. In general, each polymer layer may include any suitable polymer, such as polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and / or polysulfone, so long as the two layers are compatible with each other, as further described below in accordance with the description of FIG. 4.

[0031] Both the first polymer and the second polymer are permeable to the daughter radionuclide. For example, the diffusion coefficient of the daughter radionuclide in each polymer is at least 10 -11 cm 2 / sec. Typically, the thickness T1 of each layer is between 0.1-2 microns, such as between 0.1-1 microns. The atoms 26 may be deposited on (or in) the inner layer 30 using any of the techniques described above. (Given the relative thinness of the inner layer, the inner layer typically does not inhibit electrostatic collection of the radionuclides.)

[0032] Apparatus 21 can be configured similarly to apparatus 20. An advantage of apparatus 21 is that if the daughter nuclei of the radioactive nuclide recoil inwardly, they will diffuse outwardly through inner layer 30 and outer layer 33, so that the probability of the daughter nuclei escaping apparatus 21 can approach 100%. (Even if a particular nuclide diffuses inwardly to the outer surface of the support, the nuclei will not adhere to or penetrate the outer surface.) Thus, a desired dose of alpha particle emission can be achieved using only half the amount of radioactive nuclide atoms 26 as would be the case with apparatus 20. Thus, for example, with apparatus 21, the density of atoms 26 on inner layer 30 would be 5×10 per square centimeter. 10 -5×10 13 It can be an atom.

[0033] In general, any suitable technique can be used to apply polymer layer 28 to device 20, or inner layer 30 and outer layer 33 to device 21. One such technique for device 20 is shown in Figure 3, which is a schematic illustration of a dip coating technique for the manufacture of brachytherapy devices according to some embodiments of the present invention.

[0034] 3, to fabricate device 20, radionuclide atoms 26 are first deposited on exterior surface 24. Thereafter, the radiation source (i.e., support 22 with the radionuclide atoms deposited thereon) is immersed in a solution comprised of polymer solute 29 dissolved in solvent 34. (For ease of illustration, the dissolved polymer particles are drawn disproportionately large.) The radiation source is then withdrawn from the solution (as indicated by the upward arrow), thereby drawing solute 29 to the radiation source, such that a polymer layer 28 coats exterior surface 24. The desired thickness of polymer layer 28 can be obtained by controlling the concentration of the polymer solute and the rate at which the radiation source is withdrawn from the solution.

[0035] The dip coating technique described above can also be used to manufacture device 21. In this regard, reference is made to Figure 4, which is a flow diagram of a method 36 for manufacturing device 21 according to some embodiments of the present invention.

[0036] The method 36 begins with a first insertion step 38 where the substrate 22 is inserted into a first polymer solution. The substrate is then withdrawn from the first polymer solution and the inner layer 30 covers the substrate in a first withdrawal step 40. As with the polymer layer 28 of the device 20, the desired thickness of the inner layer 30 is achieved by controlling the concentration of the polymer solute and the rate at which the substrate is withdrawn from the solution.

[0037] Subsequently, in a deposition step 42, the radionuclide is deposited on (and / or in) the inner layer 30. Next, in a second insertion step 44, the radioactive source (i.e., the support with the radionuclide deposited thereon) is inserted into a second polymer solution that is different from the first polymer. Finally, in a second withdrawal step 46, the radioactive source is withdrawn from the second polymer solution and the outer layer 33 covers the radionuclide. As with the inner layer 30, the desired thickness of the outer layer can be obtained by controlling the concentration of the polymer solute and the rate at which the radioactive source is withdrawn from the solution.

[0038] In general, for layer 28 of device 20 and outer layer 33 of device 21, solvent 34 may comprise any suitable organic material that does not dissolve the radionuclide. Similar solvents may be used for the inner polymeric layers of device 21.

[0039] Table 1 lists, by way of example, six different solutions that can be used to form any one of the polymer layers described herein, with each row of the table (following the first row) corresponding to a different one of these solutions. [Table 1]

[0040] In the apparatus 21, the respective solutions used for the two polymer layers are selected, taking into account the constraint that the solvent used for the outer polymer layer does not dissolve the inner layer. Five different possible solution pairs are shown as examples in Table 2, using the numbering system in Table 1 to identify the solutions. [Table 2]

[0041] (Experimental Results) The inventors prepared a number of experimental brachytherapy devices using Ra-224 as the radionuclide. Each of these devices was placed in an environment simulating the inside of the human body, such as serum or water at 37°C, or a mouse tumor. For each device, no loss of radium was detected, indicating that the polymer layer covering the radium prevented it from washing away. The devices were then tested for radon desorption using alpha spectroscopy.

[0042] In the following paragraphs, the preparation of some of the experimental equipment as well as the test for radon desorption will be described in more detail.

[0043] (1) Single polymer layer Ra-224 atoms produced by the decay of thorium-228 (Th-228) were electrostatically collected on four titanium wires with a diameter of 0.5 mm. The first wire was immersed in a 5 wt% polycarbonate solution with dichloromethane (DCM) as the solvent and then withdrawn from the solution at a speed of 8 mm / s, resulting in a polymer layer thickness of about 0.25 microns. The procedure was then repeated for the second wire, with the concentration of polycarbonate increased to 7.5 wt%, resulting in a polymer layer thickness of about 0.5 microns. The third wire was immersed in a 15 wt% polydimethylsiloxane (PDMS) solution with hexane as the solvent and then withdrawn at 12 mm / s, resulting in a polymer layer thickness of about 0.25 microns. The concentration of PDMS was then increased to 30 wt%, resulting in a polymer layer thickness of about 1 micron, resulting in a polymer layer thickness of about 1 micron. The procedure was then repeated for the fourth wire, with the concentration of PDMS increased to 30 wt%, resulting in a polymer layer thickness of about 1 micron.

[0044] The measured probability of radon desorption was 50% for the first wire, 48% for the second wire, and 50% for each of the third and fourth wires. (As discussed above with reference to FIG. 1, 50% is the theoretical maximum for device 20, assuming that 50% of the radon nuclides recoil backwards into the radiation source.)

[0045] (2) Double polymer layer The titanium wire was immersed in a 2% (by weight) solution of polyethylene terephthalate (PET) in hexafluoroisopropanol (HFIP) and withdrawn at a speed of 10 mm / s, resulting in an inner layer thickness of 0.2 microns. Ra-224 atoms were then collected on the inner layer. The radioactive source was then immersed in a 3% (by weight) solution of polycarbonate in dichloromethane (DCM) and withdrawn at a speed of 10 mm / s, resulting in an outer layer thickness of 0.25 microns. The measured radon desorption probability was 88%, only slightly lower than the theoretical maximum of 100%.

[0046] (Note that the thickness of each polymer layer was measured by alpha energy loss spectroscopy as described in Kelson, I. et al., "Recoil Injection of Alpha Sources for Thin Film Thickness Measurement," Journal of Physics D: Applied Physics 28.1 (1995):100, which is incorporated herein by reference.)

[0047] Those skilled in the art will appreciate that the present invention is not limited to what has been particularly shown and described above, but rather, the scope of the present invention includes both combinations and subcombinations of the various features described above, as well as variations and modifications thereof that are not in the prior art and that would occur to one skilled in the art upon reading the above description.

Claims

1. A support having an outer surface and configured for insertion into a subject's body; a plurality of atoms of a radionuclide bound to said exterior surface and radioactively decaying to produce daughter radionuclides; a layer of polymer covering said atom that is permeable to said daughter radionuclide; An apparatus having

2. The device of claim 1 , wherein the atoms are disposed on the exterior surface.

3. 3. The device according to claim 1 or 2, wherein the support is in the shape of a cylinder.

4. The device according to any one of claims 1 to 3, wherein the radionuclide is an alpha emitting radionuclide.

5. 5. The device of claim 1, wherein the radionuclide comprises one isotope of radium selected from the group of isotopes consisting of Ra-224 and Ra-223.

6. 6. Apparatus according to any one of claims 1 to 5, wherein said daughter radionuclide is an alpha-emitting daughter radionuclide.

7. The device of any one of claims 1 to 6, wherein the layer has a thickness of 0.1-2 microns.

8. The device of claim 7, wherein the thickness is 0.1-1 microns.

9. The diffusion coefficient of the daughter radionuclide in the polymer is at least 10 -11 cm 2 The apparatus according to any one of claims 1 to 8, wherein the number of pulses per second is 1 / second.

10. The device of any one of claims 1-9, wherein the polymer is selected from the group of polymers consisting of polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and polysulfone.

11. the layer being an outer layer; the polymer is a first polymer; the device further comprises a second polymeric inner layer, the inner layer being permeable to the daughter radionuclide and coating the outer surface, the atom being bound to the outer surface by being bound to the inner layer. Apparatus according to any one of claims 1 to 10.

12. The device of claim 11, wherein the inner layer has a thickness of 0.1-2 microns.

13. The device of claim 12, wherein the inner layer has a thickness of 0.1-1 micron.

14. Attaching a plurality of atoms of a radionuclide that radioactively decays to produce a daughter radionuclide to an exterior surface of a support configured for insertion into a subject; after the step of bonding said atoms to said outer surface, covering said atoms with a layer of polymer that is permeable to said daughter radionuclide; The method according to claim 1,

15. The method of claim 14 , wherein the support is cylindrical.

16. 16. The method of claim 14 or 15, wherein the step of coating the atoms comprises pulling the support out of a solution of the polymer, whereby a layer of the polymer coats the outer surface, thereby coating the atoms.

17. The method of any one of claims 14-16, wherein the radionuclide is an alpha emitting radionuclide.

18. The method of any one of claims 14-17, wherein the radionuclide comprises one radium isotope selected from the group of isotopes consisting of Ra-224 and Ra-223.

19. 19. The method of any one of claims 14-18, wherein the daughter radionuclide is an alpha emitting daughter nuclide.

20. The method of any one of claims 14 to 19, wherein the layer has a thickness of 0.1-2 microns.

21. The method of claim 20, wherein the thickness is 0.1-1 microns.

22. The diffusion coefficient of the daughter radionuclide in the polymer is at least 10 -11 cm 2 The method of any one of claims 14 to 21, wherein the time is 1 / second.

23. The method of any one of claims 14-22, wherein the polymer is selected from the group of polymers consisting of polypropylene, polycarbonate, polydimethylsiloxane, polyethylene terephthalate, poly(methyl methacrylate), and polysulfone.

24. the layer being an outer layer; the polymer is a first polymer; The method further includes coating the exterior surface with an inner layer of a second polymer prior to the step of bonding the atoms to the exterior surface; and and bonding the atoms to the outer surface includes bonding the atoms to the outer surface by bonding the atoms to the inner layer.

24. The method according to any one of claims 14 to 23.

25. The method of claim 24, wherein the inner layer has a thickness of 0.1-2 microns.

26. The method of claim 25, wherein the inner layer has a thickness of 0.1-1 micron.

27. Inserting a radiation source into the subject, The radiation source comprises: A support having an outer surface; a plurality of atoms of a radionuclide bound to said exterior surface that undergo radioactive decay to produce daughter nuclides; a layer of polymer permeable to said daughter radionuclide and covering said atom; and leaving the radioactive source within the subject such that nuclei of the daughter radionuclide diffuse through the layer of polymer; The method according to claim 1,

28. the layer being an outer layer; the polymer is a first polymer; the radiation source further comprises an inner layer of a second polymer that is transparent to the daughter radionuclide and that coats the outer surface, the atom being bonded to the outer surface by being bonded to the inner layer; 28. The method of claim 27.

29. 29. The method of claim 27 or 28, wherein inserting the radiation source into the subject's body comprises inserting the radiation source into a tumor within the subject's body.

30. 30. The method of claim 27 or 28, wherein inserting the radiation source into the subject's body comprises inserting the radiation source such that the radiation source is within 0.1 mm of a tumor in the subject's body.

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