Patent Publication Number: US-2022212033-A1

Title: Strontium sealed source

Description:
This application is a divisional application of U.S. patent application Ser. No. 16/513,032 filed on Jul. 16, 2019 which is a continuation-in-part application of U.S. patent application Ser. No. 15/571,310, filed on Nov. 2, 2017, which claims priority of PCT/US2016/022437, filed Mar. 15, 2016, which claims priority under 35 U.S.C. 119(e) of U.S. provisional application Ser. No. 62/158,091, filed on May 7, 2015, the contents of all of which is hereby incorporated by reference in its entirety and for all purposes. 
    
    
     BACKGROUND OF THE DISCLOSURE 
     Field of the Disclosure 
     The disclosure pertains to a strontium-90 sealed source, such as may be used with treatment of the eye or other medical, brachytherapeutic or industrial processes. In particular, a relatively constant absorbed dose rate is sought throughout a target volume of tissue of therapeutic interest that is to be treated with radiation (hereinafter referred to as “a flat radiation profile”). 
     Description of the Prior Art 
     The prior art of radiological or radioactive sources of various types for medical, industrial and other processes is well-developed. For example, U.S. Pat. No. 8,430,804, entitled “Methods and Devices for Minimally-Invasive Extraocular Delivery of Radiation to the Posterior Portion of the Eye”, issued on Apr. 30, 2013 to Brigatti et al., and assigned on its face to Salutaris Medical Devices, Inc., discloses an applicator for minimally-invasive delivery of beta radiation from a radionuclide brachytherapy source to the posterior portion of the eye. In particular, this is adapted for the treatment of various diseases of the eye, such as, but not limited to, wet age-related macular degeneration. Other prior art includes U.S. Pat. No. 9,873,001 entitled “Methods and Devices for Minimally-Invasive Delivery of Radiation to the Eye”, issued on Jan. 23, 2018 to Lutz et al. and assigned on its face to Salutaris Medical Devices, Inc.; PCT/US2014/056135 entitled “Radiation System with Emanating Source Surrounding an Internal Attenuation Component”, filed on Mar. 18, 2016; U.S. Pat. No. 7,070,554 entitled “Brachytherapy Devices and Methods of Using Them”, issued on Jul. 4, 2006 to White et al., and assigned on its face to Theragenics Corporation and U.S. Pat. No. 6,443,881, entitled “Ophthalmic Brachytherapy Device”, issued on Sep. 3, 2002 to Finger. 
     While this prior art is well-developed and suited for its intended purposes, further improvements are sought in the radioactive sources used in the disclosed devices. In particular, a collimated distribution of radiation, rather than an isotropic (spherical “4π”) distribution of radiation, would allow a radiological source to direct radiation at the tissues under treatment, while reducing radiation directed at surrounding tissues which are not under treatment and also while preventing excessive radiation to be directed to the tissues under treatment in the center of the emitted radiation beam. 
     OBJECTS AND SUMMARY OF THE DISCLOSURE 
     It is therefore an object of the present disclosure to provide improvements in the radiological sources used in brachytherapy and in other medical or industrial applications. In particular, it is an object of the present disclosure to provide improved radiological sources for known applicators for treatment of diseases of the eye, including, but not limited to, wet age-related macular degeneration. These radiological sources are intended to concentrate the radiation more uniformly on the diseased tissue, rather than using isotropic radiation which would expose more of the surrounding healthy tissue to unnecessary radiation and could overexpose tissue under treatment at the center of the radiation beam. 
     This and other objects are attained by providing a beta radiological source, typically containing strontium-90, wherein the radiological insert has increased radioactivity around its periphery and less radioactivity at its center. This may be achieved by a toroidal or annular shape, (such as a donut-type shape with a hole or aperture in the middle) or with the central portion of a disk having reduced thickness or reduced radioactivity content. This may further be achieved by a minus lens meniscus shape wherein the lower concave surface has a shorter radius of curvature than the upper concave surface, thereby resulting in a raised thinner portion and a lower thicker peripheral portion. This is further achieved by providing an encapsulation with increased shielding in the center of the face from which the therapeutic radiation is emitted, thereby substantially attenuating the radiation emitted from the central portion of a source. It is further possible to use a separate denser attenuating disk in front of the activity, either on the inside or outside of the encapsulation. Material in the attenuating disk may include, but is not limited to, silver, copper, lead, tungsten, gold and/or iridium. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further objects and advantages of the disclosure will become apparent from the following description and from the accompanying drawings, wherein: 
         FIG. 1  is a cross-sectional view of an embodiment of a radiological source of the present disclosure. 
         FIG. 2  is an illustration relating to the radiation dose profile generated by the radiological source of  FIG. 1 . 
         FIGS. 3A-3F  illustrates various further embodiments of the radiological source of the present disclosure. 
         FIG. 4  illustrates a placement of the radiological source with respect to a human eyeball during medical treatment. 
         FIG. 5  illustrates a portion of  FIG. 4  in greater detail. 
         FIG. 6  illustrates a still further embodiment of the radiological source of the present disclosure, including a minus-lens meniscus shape. 
         FIGS. 7A and 7B  illustrate a still further embodiment of the radiological source of the present disclosure, wherein multiple elements are placed in a quasi-toroidal shape in one or two layers. 
         FIGS. 8A, 8B and 8C  illustrate yet still further embodiments of the radiological source of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring now to the drawings in detail wherein like numerals refer to like elements throughout the several views, one sees that  FIG. 1  illustrates a cross-sectional view of an embodiment of the radiological source  100 . The radiological source  100  is substantially rotationally symmetric, including cylindrical, annular and toroidal shapes. A capsule body  300 , typically made of titanium or stainless steel, includes a lower floor  302  with a central plateau  304  thereby forming a toroidal channel  306  between the central plateau  304  (thereby increasing the beta shielding in central portions of the lower floor  302 ) and the outer cylindrical wall  308  of the capsule body  300 . The upper edge of outer cylindrical wall  308  forms a circular opening for receiving outer lid  310  which is generally cylindrical but includes a chambered lower circular edge  312  and further includes a central cylindrical blind opening  314  for receiving telescoping inner lid  316 , and typically forming a tight friction or interference fit therebetween in order to tightly position the radiological insert  318  within the capsule body  300 . Outer lid  310 , which is typically made of titanium or stainless steel and illustrated with an interior circumferential toroidal ridge  327 , is typically welded to capsule body  300 , using conventional standards of the industry. Strontium-90 radiological insert  318  (similar to insert  130  in previous embodiments) includes an upper circular or disk-shaped portion  320  which is engaged between a lower edge of telescoping inner lid  316  and central plateau  304  of capsule body  300 . This configuration is intended to reduce rattling of the strontium-90 radiological insert  318 . The upper surface of strontium-90 radiological insert  318  includes a convex central region  325 . This convex central region  325  is intended to reinforce the structure and avoid or minimize warping and possible delamination during production. Strontium-90 radiological insert  318  further includes a downwardly extending circumferential toroidal portion  323  which extends into toroidal channel  306  of capsule body  300 . 
     The toroidal shape of the strontium-90 radiological insert  318 , with its thickened periphery, leads to increased radiation emission around the periphery and a reduced radiation output within the center. This, in combination with the increased beta shielding in the central area of central plateau  304 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source as illustrated in  FIG. 2 , wherein typical values are given for a radiological source  100  of a diameter of 4.05 millimeters and a maximum height of 1.75 millimeters. In the given example, a intended therapeutic volume  400  with a diameter of 3.0 millimeters and a depth of 1.438 to 2.196 millimeters (with a mean depth to target of 1.817 millimeters from the lower surface of the radiological source  100 ) in a first case or a depth of 1.353 to 2.111 millimeters (with a mean depth to target of 1.752 millimeters from the lower surface of the radiological source  100 ) in a second case. A radius of 11.50 millimeters is typical for the sclera  2002  (outer covering) of a human eyeball  2000  (see also  FIGS. 4  and  5 ). Those skilled in the art, after review of this disclosure, will understand that different structural parameters will result in different radiation distributions, as may be required by the specific application. 
     It is noted that the strontium-90 beta radiation insert  130  may be made of various materials, such as a strontium ceramic, strontium glass, or a collection of tightly packed ceramic beads (of various possible shapes) or a refractory-metal composite. Refractory ceramics and glasses containing Strontium-90 can be made from a wide variety of materials in combination, such as those containing metal oxides of aluminum, silicon, zirconium, titanium, magnesium, calcium amongst others. It is envisioned that other additional materials may be selected from, but not limited to, such strontium-90 compounds as SrF 2 , Sr 2 P 2 O 7 , SrTiO 3 , SrO, Sr 2 TiO 4 , SrZrO 3 , SrCO 3 , Sr(NbO 3 ) 2 , SrSiO 3, 3 SrO.Al 2 O 3 , SrSO 4 , SrB 6 , SrS, SrBr 2 , SrC 2 , SrCl 2 , SrI 2  and SrWO 4 . Additionally, beta emitters based on materials other than strontium-90 may also be compatible with this disclosure. Such beta emitters may include Copper-66, Lead-209, Praseodymium-145, Tellurium-127, Tin-121, Nickel-66, Yttrium-90, Bismuth-210, Erbium-169, Praseodymium-143, Phosphorus-32, Phosphorus-33, Strontium-89, Yttrium-91, Tungsten-188, Sulfur-35, Tin-123, Calcium-45, Berkelium-249, Ruthenium-106, Thulium-171, Promethium-147, Krypton-85, Hydrogen-3, Cadmium-113m, Plutonium-241, Strontium-90, Argon-42, Samarium-151, Nickel-63, Silicon-32, Argon-39, Carbon-14, Technetium-99, Selenium-79, Beryllium-10, Cesium-135, Palladium-107, Rhenium-187, Indium-115 and Cadmium-113. In particular, after commercial and technical considerations (e.g., energy level and half-life), the following are of particular interest—Strontium-90/Yttrium-90, Strontium-89, Phosphorus-32, Tin-123 and Yttrium-91. 
       FIGS. 3A through 3F  illustrate six further design embodiments of radiological source  100  of the present disclosure. The radiological source  100  of  FIG. 3A  is very similar to  FIG. 1  and includes capsule body  300  includes a lower floor  302 , the interior wall of the lower floor  302  including a central plateau  304  on the interior thereof thereby forming a toroidal channel  306  between the central plateau  304  and the outer cylindrical wall  308  of the capsule body  300 . The upper edge of outer cylindrical wall  308  forms a circular opening for receiving outer lid  310  which is generally cylindrical. Outer lid  310  is typically welded to capsule body  300 , using conventional standards of the industry. Strontium-90 radiological insert  318  is toroidally shaped by rotating a rectangular cross-section about the central axis thereby resulting in a central passageway  319 . Toroidally-shaped radiological insert  318  is positioned above the toroidal channel  306 , and supported by central plateau  304  and shoulder  308 A,  308 B formed within an interior of outer cylindrical wall  308 . A cylindrical disk-shaped spacer  320 , typically made of titanium or stainless steel, is positioned between the radiological insert  318  and the lower surface of the outer lid  310 . Additionally, a cylindrical shielding insert  322 , typically made from titanium or stainless steel, inserted within the central aperture  319 . The shape of the strontium-90 radiological insert  318  leads to increased radiation output around the periphery, with a reduced radiation output within the central aperture  319 . This, in combination with the increased shielding in the central area of central plateau  304  and the cylindrical shielding insert  322 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source (i.e., anisotropic) characteristic of the resulting beta radiation. 
     The embodiment of radiological source  100  in  FIG. 3B  is similar to that of  FIG. 3A . The interior wall of lower floor  302  is generally planar without the central plateau of  FIG. 3A . The toroidal-shaped strontium-90 radiological insert  318  is secured to cylindrical disk-shaped spacer  320  by a low-melting glass bond  321  or similar configuration. Cylindrical shielding insert  322  extends from spacer  320  to the inner wall of lower floor  302 , thereby resulting in a configuration with a toroidal-shaped void 306′ below the toroidal-shaped strontium-90 radiological insert  318 . The shape of the strontium-90 radiological insert  318  leads to an increased radiation source around the periphery, with a removal of a source of radiation within the central aperture  319 . This, in combination with the increased shielding of the cylindrical shielding insert  322 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source). 
     The embodiment of radiological source  100  in  FIG. 3C  is similar to that of  FIG. 3A . The toroidal-shaped strontium-90 radiological insert  318  includes a central cylindrical disk portion  318 A and further includes upper and lower toroidal portions  318 B,  318 C, respectively, extending around the circumference thereof. Additionally, spacer  320  further includes a downwardly extending cylindrical skirt  320 A which outwardly abuts the circumference of toroidal-shaped strontium-90 radiological insert  318 . Spacer  320  further includes a central cylindrical aperture  320 B which receives a variation of shielding insert  322 , further including a downwardly extending frusto-conical portion  322 A for engaging against central cylindrical disk portion  318 A of strontium-90 radiological insert  318  and being positioned within the upper toroidal portion  318 B of strontium-90 radiological insert  318 . This configuration engages the central cylindrical disk portion  318 A between the downwardly extending frusto-conical portion  322 A of shielding insert  322  and central plateau  304 . Similar to the embodiment of  FIG. 3B , a toroidal-shaped void 306′ is formed between the lower toroidal portion  318 C of strontium-90 radiological insert  318  and the inner wall of floor  302 . The shape of the strontium-90 radiological insert  318  leads to an increased radiation source around the periphery, with a reduction in the radiation from cylindrical disk portion  318 A. This, in combination with the increased shielding of the central plateau  304 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source). 
     The embodiment of  FIG. 3D  is similar to that of  FIG. 3B . However, the interior of cylindrical wall  308  includes shoulders  308 A,  308 B for supporting the toroidal-shaped strontium-90 radiological insert  318  above the toroidal channel  306 . This may eliminate the need for the low melting glass bond  321  or similar configuration to affix the toroidal-shaped strontium-90 radiological insert  318  to the spacer  320 . The shape of the strontium-90 radiological insert  318  leads to an increased radiation source around the periphery, with a removal of a source of radiation within the central aperture  319 . This, in combination with the increased shielding of the cylindrical shielding insert  322 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source). 
     The embodiment of  FIG. 3E  is similar to that of  FIG. 3C . The toroidal-shaped strontium-90 radiological insert  318  includes a central cylindrical disk portion  318 A and further includes a lower toroidal portion  318 C extending around the circumference thereof. The lack of a upper toroidal portion allows the spacer  320  to be simplified to a cylindrical disk shape. The shape of the strontium-90 radiological insert  318  leads to an increased radiation source around the periphery, with a reduction in the radiation from cylindrical disk portion  318 A. This, in combination with the increased shielding of the central plateau  304 , results in a flat beam profile, achieving a more constant absorbed dose rate throughout a target volume of tissue of therapeutic interest that is located in front of the source). 
     The embodiment of  FIG. 3F  is similar to that of  FIG. 3E . The strontium-90 radiological insert  318  is simplified to a disk shape, rather than a toroidal shape. Additionally, spacer  320  further includes a downwardly extending cylindrical skirt  320 A which outwardly abuts the circumference of toroidal-shaped strontium-90 radiological insert  318 . The strontium-90 radiological insert  318  is secured to cylindrical disk-shaped spacer  320  by a low-melting glass bond  321  so as to be suspended above central plateau  304  and toroidal channel  306 . It is envisioned that this embodiment could further have the strontium-90 radiological insert  318  contacting and being supported, at least in part, by central plateau  304 . 
     The embodiment of  FIG. 6  is a Strontium-90 radiological insert  500  with a (rotationally symmetric) minus-lens meniscus shape wherein there are two different curvatures on the upper and lower surfaces  502 ,  504 . The upper surface  502  (or “rear”) is convex, the lower surface  504  (or “face”) is concave  504  and the radiological insert  500  is thinner at its center  510  (i.e., along the rotational axis) than at its edges  512 ,  514 . Typically, this minus-lens meniscus shape may be implemented by having a shorter radius of curvature for the lower surface  504  than for the upper surface  502 . While not shown, this radiological insert  500  will typically be encased by an encapsulation or capsule body  300  similar to that shown in  FIGS. 3A-3F , possibly with increased shielding in a central portion thereof (that is, below the center  510 ) in order to achieve a flatter radiation profile. This meniscus configuration may be considered, from a mathematical point of view, to be mid-way between a cylindrical or flat disk and a toroidal “donut-shaped” configuration. The configuration may be termed “meniscus,” “biconcave,” or “planar concave.” 
     The embodiment of  FIG. 7A  illustrates a Strontium-90 radiological insert  600  comprising a ring of disk-like sub-elements of Strontium-90  602  arranged in a quasi-toroidal shape. Similarly, the embodiment of  FIG. 7B  illustrates a Strontium-90 radiological insert  600  comprising a first ring of disk-like sub-elements of Strontium-90  602  arranged in a quasi-toroidal shape, with second ring of disk-like sub-elements of Strontium-90  604 , rotationally offset by the radius or one half of the expanse of one disk from the first ring, and axially offset, typically by the thickness of the sub-elements  602 ,  604 . The first and second rings are adjacent to each other and share a common rotational axis  606 . The embodiments of  FIGS. 7A and 7B  further include a sealed encapsulation. 
     The embodiments of  FIGS. 8A, 8B and 8C  include a metallic, ceramic or similar dish  700  into which fused Sr-90 glass  702  is melted and bonded. The Sr-90 glass  702 , in a viscous state, is poured into the dish in an inverted position from that shown in  FIGS. 8A, 8B and 8C  so as to form a meniscus  704  (the illustrated concave surface). In order to increase the amount of Sr-90 glass at the peripheral portions of the dish  700 , toroidal troughs  706  may be formed such as is illustrated in  FIGS. 8A and 8B . These embodiments of  FIGS. 8A, 8B and 8C  further include a sealed encapsulation. 
     Further alternatives to the present disclosure include fixation of the active insert using glass, such as glass pre-melted into a stainless steel insert, glass powder co-compacted with a ceramic and glass powder mixed with a ceramic and then compacted. Additionally, alternatives include fixation of the active insert using mechanical methods such as soft materials such as copper, silver, aluminum, etc. or the use of springs of various types (wave, conical, folded disk, etc.). Further alternatives include active insert centering features to prevent positional errors such as tapered ceramic disks or a disk with an aperture or protrusion which interfaces with the capsule lid. 
     Similarly, the various embodiments of the radiological sources which include a cavity could be implemented by filling the cavity with radioactive microspheres. Such shapes would be defined by the shape of the cavity inside the source, while the microspheres could be immobilized using washers, spaces or similar devices during assembly. Further alternative embodiments include radioactive microspheres which are bonded using a fused glass/enamel bonding material to an insert (e.g., a metal or ceramic support) to immobilize the microspheres and define their shape. 
     In a further aspect of this disclosure, aqueous ammonia solution (NH 4 OH) is added to a mixed aqueous solution containing dissolved radioactive strontium nitrate  90 Sr(NO 3 ) 2  and dissolved silver nitrate (AgNO 3 ) (gold or copper may be substituted for silver in some applications, mixtures of silver, gold or copper may also be used) and a mixed precipitate can form of sparingly soluble silver hydroxide AgOH (some of which may convert to silver oxide Ag 2 O plus water in situ) and strontium hydroxide  90 Sr(OH) 2 . Soluble ammonium nitrate NH 4 NO 3  remains in solution. Excess ammonium hydroxide produces a water-soluble ammoniacal silver complex [Ag(NH 3 ) 2 OH] while the strontium hydroxide remains insoluble. The solution and/or the mixed precipitates can be evaporated so that all solids co-precipitate or crystalize out of solution to produce an intimate mixture. These solids are baked dry so that the ammonium nitrate decomposes and sublimes (above 250° Centigrade) leaving substantially nothing behind, silver hydroxide decomposes to silver oxide then further decomposes to silver metal and the strontium hydroxide decomposes to strontium oxide. What is left is an intimate mixture of silver metal and strontium oxide ( 90 SrO+Ag). Because silver is a soft semi-precious metal, such an intimate mixture of silver and radioactive strontium oxide can be mechanically and/or thermally formed into thin toroidal insert shapes by processes such as pressing, forging, rolling, extrusion and/or sintering. 
     Silver hydroxide or silver oxide can be prepared and pressed into a disk shape (toroidal or flat) at a pressure sufficient to bind the particles together to produce a handleable green-state disk (an organic or inorganic binder can be added if needed) but at a pressure that is low enough to leave porosity or microporosity within the disk. Aqueous strontium nitrate  90 Sr(NO 3 ) 2  can then be soaked into the disk and then dried down to achieve intimate mixing. The dried disk can be sintered to produce a fully dense cermet containing strontium oxide embedded or immobilized within the matrix formed of copper oxide, silver oxide, copper hydroxide, silver hydroxide, gold hydroxide (i.e., auric acid) or mixtures thereof. The proportions of strontium and silver (or gold, copper or mixtures thereof) can be varied, resulting in different mechanical properties. Less strontium produces more ductility but a thicker more-attenuating disk. The typical range of composition can be 2-50 mol percent of strontium oxide in silver, gold or copper, preferably 5-40 mol percent, more preferably 10-30 mol percent. Cermet disks can be re-pressed or otherwise mechanically or thermally treated after sintering to further densify or remold the shape of the disks. 
     In a further aspect of this disclosure, Strontium-90 compounds are incorporated or mixed with aluminum to make a composite material. This may be performed by a method of incorporating Strontium-90 into aluminum by mixing or blending strontium fluoride ( 90 SrF 2 ) powder with aluminum powder, compressing the mixture into a billet, then heating it to about 10° Centigrade below the melting point of aluminum (660.3° Centigrade) before extruding the billet through an aperture in a metal collar to produce a wire of  90 SrF 2 +Al. The resulting material can be formed into a toroidal disk or similar configuration as described in this disclosure. 
     Strontium fluoride is a stable material. It melts at 1477° Centigrade and is insoluble in water (K sp  value is approximately 2.0×10 −10  at 25° Centigrade). It can be made from commercially available strontium nitrate  90 Sr(NO 3 ) 2  by adding soluble ammonium fluoride to a strontium nitrate solution, precipitating insoluble strontium fluoride ( 90 SrF 2 ) and mixing/blending the dried salt with aluminum powder before pressing the mixture/blend into a disk. Useful ratios of  90 SrF 2  to Al could typically be in the range 5-50% of  90 SrF 2 , preferably 10-30% (by weight). The resulting material can be formed into a toroidal disk or similar configuration as described in this disclosure. 
     Alternatively, an aqueous solution of  90 Sr(NO 3 ) 2  could be absorbed into a disk made of porous or microporous aluminum and then dried down and baked above the decomposition temperature of  90 Sr(NO 3 ) 2  of 570° Centigrade but below the melting point of aluminum 660.3° Centigrade in a non-oxidizing atmosphere, to convert the strontium nitrate into strontium oxide. This could be achieved in a vacuum oven or under an inert gas such as argon or a reducing atmosphere such as an argon-hydrogen mixture. Other soluble forms of Strontium-90 could be absorbed and baked in similar ways. The resulting material can be formed into a toroidal disk or similar configuration as described in this disclosure. 
     Thus the several aforementioned objects and advantages are most effectively attained. Although preferred embodiments of the invention have been disclosed and described in detail herein, it should be understood that this invention is in no sense limited thereby.