Patent Publication Number: US-6666812-B2

Title: Radioactive therapeutic seeds

Description:
This is a continuation of application Ser. No. 09/860,405, filed May 18, 2001 now U.S. Pat. No. 6,471,632. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The invention relates to radioactive therapeutic seeds. More particularly, the invention relates to improved radioactive therapeutic seeds for the treatment of oncological and other medical conditions. 
     2. State of the Art 
     Radioactive seed therapy is a well known and well accepted medical procedure for the treatment of various oncological and other medical conditions. Seed therapy, also known as brachytherapy typically involves the implantation of fifty to one hundred tiny capsules (seeds) into or around a treatment site. The capsules contain a radioactive isotope which irradiates the treatment site at close range without adversely affecting other parts of the body. Brachytherapy has been used successfully in the treatment of various types of cancers such as prostate cancer. It has also been used to prevent the growth or regrowth of tissues in the treatment of various occlusive diseases such as arteriosclerosis and arthrosclerosis subsequent to balloon angioplasty. 
     Radioactive therapeutic seeds are carefully designed to possess several important qualities. First, they are relatively small, typically approximately 0.025 inch in diameter and approximately 0.16 inch long so that they may be implanted using minimally invasive instruments and techniques. Second, the radioactive isotope must be enclosed in a biocompatible protective package since the seeds are typically not removed and will remain in the body for many years. Third, each seed preferably includes a radiopaque (e.g. high Z material) marker so that it can be located at the treatment site with the aid of fluoroscopy. Fourth, the protective package and the radiopaque marker preferably do not cast “shadows” in the irradiation pattern of the isotope. Fifth, the isotope should be evenly distributed within the protective package so as to avoid any “hot spots” of radiation. 
     The state of the art of radioactive therapeutic seeds is substantially disclosed in several co-owned patents to Slater et al. including U.S. Pat. Nos. 6,007,475, 6,066,083, 6,080,099, 6,200,316, 6,210,316 as well as eight additional U.S. Pat. No. 6,099,458 to Robertson for “Encapsulated Low-Energy Brachytherapy Sources”, U.S. Pat. No. 5,713,828 to Coniglione for “Hollow-Tube Brachytherapy Device”, U.S. Pat. No. 5,405,309 to Carden, Jr. for “X-Ray Emitting Interstitial Implants”, U.S. Pat. No. 4,891,165 to Suthanthiran for “Device and Method for Encapsulating Radioactive Materials” and U.S. Pat. No. 4,784,116 to Russell, Jr. et al. for “Capsule for Interstitial Implants”, U.S. Pat. No. 4,702,228 to Russell, Jr. et al. for “X-Ray Emitting Interstitial Implants”, U.S. Pat. No. 4,323,055 to Kubiatowicz for “Radioactive Iodine Seed”, and U.S. Pat. No. 3,351,049 to Lawrence for “Therapeutic Metal Seed Containing within a Radioactive Isotope Disposed on a Carrier and Method of Manufacture”. 
     The Lawrence patent describes many of the essential features of radioactive therapeutic seeds. Lawrence describes radioactive isotopes (I-125, Pd-103, Cs-131, Xe-133, and Yt-169) which emit low energy X-rays and which have relatively short half-lives. When implanted at a treatment site, these isotopes provide sufficient radiotherapy without posing a radiation danger to the medical practitioner(s), people in the vicinity of the patient, or other parts of the patient&#39;s body. Lawrence further describes a protective capsule which contains the isotope and prevents it from migrating throughout the body where it might interfere with healthy tissue. The capsule is cylindrical and made of low atomic number biocompatible materials such as stainless steel or titanium which substantially do not absorb X-rays. The isotope is coated on a rod shaped carrier made of similar X-ray transparent (e.g. low Z) material and is placed inside the capsule cylinder. The ends of the capsule cylinder are closed by swaging or spinning and soldering or welding. According to a preferred embodiment, Lawrence places a radiopaque marker inside the seed. In one embodiment, the marker is a wire embedded inside the carrier rod. The wire is made of high atomic number material such as gold or tungsten which absorb X-rays. 
     In 1980, Kubiatowicz made a minor improvement in the basic Lawrence design by providing that the entire isotope carrier be made of radiopaque material such as silver. Kubiatowicz recognized that since the isotope was carried on the entire outer surface of the carrier, there was no need to make the carrier body X-ray transparent as suggested by Lawrence. The larger radiopaque carrier body described by Kubiatowicz makes the seeds easier to see with X-ray or fluoroscopic examination. Thus, the seeds may be placed more accurately at or around the treatment site. 
     Several years later, Russell, Jr. et al., in U.S. Pat. Nos. 4,707,228 and 4,784,116, explained that the capsule design of Lawrence and Kubiatowicz produces anisotropic angular radiation distribution. According to Russell, Jr. et al., the shell forming techniques used in the Lawrence-type seeds results in large beads of shell material at the ends of the seeds. These beads substantially shield radiation thereby casting shadows in the irradiation pattern of the isotope. Russell, Jr. et al. proposed a new seed design to solve this problem. In particular, Russell, Jr. et al. proposed a seed having a cylindrical container which is sealed with end caps which have a wall thickness that is substantially the same as the wall thickness of the cylindrical container. The end caps are attached to the cylindrical container by welding or crimping. 
     An alternate solution to the non-uniform radiation pattern of the Lawrence type seeds was proposed by Suthanthiran in U.S. Pat. No. 4,891,165. Suthanthiran&#39;s solution was to form a seed capsule from two interfitting sleeves, each having one open end and one closed end. The thickness of the sleeve side walls and their closed ends is such that when the sleeves are interfit in an overlapping manner, the total side wall thickness of the assembled capsule is approximately equal to the end wall thickness. 
     Other improvements in radioactive therapeutic seeds are disclosed in U.S. Pat. No. 5,405,309 which concerns a safe isotopically pure Pd-103 seed, U.S. Pat. No. 5,713,828 which discloses a hollow tube seed which can be implanted with suture material, and U.S. Pat. No. 6,099,458 which discloses a seeds which are manufactured in a simplified manner which includes placing sources in titanium capsule halves, providing a titanium plug having a marker therein internal the capsule halves, and welding the titanium capsule halves to the titanium plug. 
     Despite the fact that radioactive therapeutic seeds have been in use for over thirty years and despite the several significant improvements made in these seeds, many concerns still exist regarding their design and construction. For example, while significant attention has been given to the methods by which a cylindrical seed capsule is sealed, it is still difficult to seal such a small cylindrical capsule without adversely affecting the functionality of the seed. Most capsules are sealed at an end using solder which causes a shadow and consequent anisotropic radiation distribution, and while the U.S. Pat. No. 6,200,258 to Slater et al., and U.S. Pat. No. 6,099,458 to Robertson overcome some of these problems, they still suffer from issues regarding thick plugs of titanium around the markers which can affect the isotropic distribution of radiation. 
     SUMMARY OF THE INVENTION 
     It is therefore an object of the invention to provide radioactive therapeutic seeds which have a relatively isotropic radiation pattern. 
     It is also an object of the invention to provide radioactive therapeutic seeds which are easy to manufacture. 
     It is another object of the invention to provide radioactive therapeutic seeds which can be deployed relatively quickly and easily. 
     In accord with these objects which will be discussed in detail below, the radioactive therapeutic seeds of the present invention include a substantially radiotransparent cylindrical capsule containing a radioactive isotope and preferably a radiopaque marker. Each of the embodiments is designed to provide a substantially isotropic distribution of radiation. As used herein, the terms “radiotransparent”, “radiolucent”, “radiotranslucent”, and “low Z material” are used interchangeably. 
     According to a first embodiment of the invention, the isotope is deposited on the outer surface of a hollow radiolucent tube and a ceramic collar having a metal ring centrally located thereon is preferably tightly fit about a central portion of the tube. The capsule comprises two tubular halves, each having a closed end and an open end. The halves of the capsule are positioned over the tube with the open ends of the halves being interference fit with the collar and abutting the metal ring. The capsule halves, typically formed of titanium, are welded to the ring (also typically formed of titanium) to seal the capsule. The ceramic collar protects the contents of the capsule from the heat of welding and is even more radiotransparent than the titanium, and therefore does not affect the radiation pattern of the seed. 
     According to a second embodiment of the invention, the isotope bearing structure may be one or more radiolucent particles, preferably made from titanium, aluminum or glass, and preferably spherically shaped. The particles are provided with a thin coating of silver to facilitate the adhesion of the isotope thereto. Also provided is a tubular ceramic spacer having an axial radiopaque marker therein and a titanium ring thereon. The titanium ring provides a surface to which the open ends of the two halves of the capsule are butt against and welded. 
     According to a third embodiment of the invention, the isotope bearing structure is preferably a pair of silver tubes having outer and inner surfaces on which the isotope is provided. One silver tube is positioned in each half of the capsule, and the halves of the capsule are welded about a titanium ring which is fit over a centrally located tubular ceramic spacer. The spacer is preferably provided with a radiopaque marker therein. In addition, the isotope bearing tube is preferably smaller than the interior of each half of the capsule, and additional spacers are preferably provided in each half of the capsule between the tube and the ceramic spacer to prevent relative movement of the tube within the capsule. 
     In each of the first three embodiments, it is preferred that the ring surrounding the ceramic spacer be made of the same material as the walls of the capsule halves. Depending upon the process of joining the capsule halves, the ring may be the same thickness as the walls of the capsule halves or may have a slightly greater thickness (e.g., up to 0.005 inches thicker) than the capsule halves so that the ring stands proud of the capsule halves, provided that after joining the capsule halves together, the ring is substantially flush with (within a few thousands of an inch) the capsule halves. In addition, in each of the first three embodiments it will be appreciated that the halves of the capsule do not overlap each other and the configuration of the capsule, isotope, and ceramic spacer or collar provide the seed with a highly isotropic distribution of radiation. 
     According to a fourth embodiment of the invention, the isotope bearing structure may be one or more radiolucent particles, preferably made from titanium, aluminum or glass, and preferably spherically shaped. The particles are preferably provided with a thin coating of silver to facilitate the adhesion of the isotope thereto. Also provided is a tubular ceramic spacer having an axial radiopaque marker therein. The tubular ceramic spacer and radiopaque marker may each be formed from one or two pieces. Where the tubular ceramic spacer and radiopaque marker are formed from two pieces, a first spacer with a first marker therein is press fit into an open end of a first half of the capsule, while a second spacer with a second marker therein is press fit into an open end of a second half of the capsule. The first and second halves of the capsule are then abutted and welded. Where the ceramic spacer and radiopaque marker are each formed from one piece, the spacer, with the marker therein, is press fit partially into the open end of a first half of the capsule, and the open end of the second half of the capsule is then press fit over the remainder of the spacer to abut the first half of the capsule. The two capsule halves are then welded. Alternatively, the open ends of the capsule halves may be thinned and the open end of the second capsule half may be forced over the open end of the first capsule half. The capsule halves may then be joined by welding, swaging, or other means. 
     Additional objects and advantages of the invention will become apparent to those skilled in the art upon reference to the detailed description taken in conjunction with the provided figures. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is an enlarged schematic longitudinal section of a radioactive therapeutic seed according to a first embodiment of the invention; 
     FIG. 2 is an enlarged schematic longitudinal section of a radioactive therapeutic seed according to a second embodiment of the invention; 
     FIG. 3 is an enlarged schematic longitudinal section of a radioactive therapeutic seed according to a third embodiment of the invention. 
     FIGS. 4 a  and  4   b  are enlarged schematic longitudinal sections of a radioactive therapeutic seed according to alternative fourth embodiments of the invention. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Referring now to FIG. 1, according to a first embodiment of the invention, a radioactive therapeutic seed  10  includes an inner tube  12  having an inner surface  14  and an outer surface  16  both bearing a radioactive isotope coating  18 , a ceramic collar  20  provided about a central portion of the outer surface  16  of the tube  12 , a radio-transparent/translucent (low Z) ring or washer  21  provided about a central portion of the ceramic collar  20 , and a radio-transparent/translucent (low Z) capsule  22  which abuts the ring  21  and encloses the tube  12  and collar  18 . 
     The inner tube  12  is preferably comprised of titanium, aluminum or other substantially radiolucent material. A silver coating is preferably provided to both the inner and outer surfaces  14 ,  16  to facilitate and enhance adhesion of the isotope coating  18  thereto. In the preferred embodiment, the isotope  18  does not coat the very end (longitudinal) surfaces  24 ,  26  of the tube  12  because such a coating has been found to undesirably affect the radiation distribution of the seed  10 . The collar  20  is preferably comprised of a ceramic (e.g., alumina or zirconia). If desired, a portion of the collar (e.g., an inner surface, an outer surface, or the ends) may be made from gold which due to its radiopaque properties will act as a marker for the seed. Additionally or alternatively, a portion of the collar  20  may be comprised of a paramagnetic or diamagnetic substance, e.g., a gadolinium metal or salt, to permit visualization of the seed with magnetic resonance imaging (MRI). It is desirable that the collar  20  be tightly formed about the tube  12 . The collar  20  is also preferably provided with tapered edges  28 ,  30  to facilitate movement of the two halves  34 ,  36 , of the capsule  22  over the collar. The ring  21  about the collar  20  is preferably machined or etched from titanium or another radiolucent material, and the capsule halves  34 ,  36  are preferably machined or etched from an identical material; although, if desired, the capsule halves may be made as drawn tubes which are provided with thick bases (closed ends  38 ,  40 ) from which engaging means or connectors can be machined or etched. Thus, each half  34 ,  36  includes a closed end  38 ,  40  and an open end  42 ,  44 , respectively; and each closed end  38 ,  40  is preferably provided with an engaging means or connector  46 ,  48 , described in more detail in previously incorporated U.S. Ser. No. 09/312,215. In assembly, the halves  34 ,  36  of the capsule  22  are positioned over the tube  12  with the open ends  42 ,  44  of the halves guided by the tapered edges  28 ,  30  to form a preferably tight interference fit with the ceramic collar  20 . The open ends  42 ,  44  abut the ring  21  and are butt welded or otherwise welded to the ring  21  to seal the capsule  22  thereby providing the seed with a substantially cylindrical wall of uniform thickness. The ceramic collar  20  protects the contents of the capsule from the heat of welding. For purposes herein, the term “weld” is to be understood in its broadest sense to include any electrical, thermal, or chemical mechanism (or combination thereof) which causes the capsule halves and ring to become integral. 
     While the ring  21  is shown in FIG. 1 as having the same thickness as the walls of the capsule halves, it will be appreciated that prior to welding, the ring  21  may be thicker and stand proud of the open ends of the capsule halves. It is desirable, however, that upon completion of manufacture, the ring is substantially flush (within 0.003 inches) and integrated with the capsule halves. 
     Turning now to FIG. 2, a second embodiment of a therapeutic seed  110  according to the invention is shown. The seed  110  includes a preferably titanium capsule  122  defined by two halves  134 ,  136 , each having a closed end  138 ,  140  provided with an engagement means or connector  146 ,  148 , an open end  142 ,  144 , and an interior portion  174 ,  176 . In the interior portion  174 ,  176  of each half  134 ,  136  of the capsule  122 , isotope bearing structures  178  spaced by a central ceramic spacer  120  are provided. Preferably, the isotope bearing structures  178  are one or more radiolucent particles, preferably made from titanium, aluminum or glass, and preferably spherically shaped. The particles  178  are provided with a thin coating of silver over which the isotope  118  is provided. The ceramic spacer  120  is a generally hollow cylindrical spacer which carries an axial radiopaque marker  170  therein. A small titanium ring  121  is provided around the central portion of the spacer  120 . The spacer  120  preferably includes tapered ends  128 ,  130  to facilitate positioning the open ends  142 ,  144  of the capsule thereover. When the open ends  142 ,  144  of the halves  134 ,  136  of the capsule are placed over the spacer  120 , the ends abut the titanium ring  121  and are welded (in any manner) thereto. The result is a capsule  122  which has a substantially uniform wall thickness. 
     Referring now to FIG. 3, a third embodiment of a therapeutic seed  210  according to the invention is shown. The seed  210  includes a radiolucent titanium capsule  222  defined by two halves  234 ,  236 , each having a closed end  238 ,  240  provided with an engagement means  246 ,  248 , an open end  242 ,  244 , and an interior portion  274 ,  276 . In the interior portion  274 ,  276  of each half  234 ,  236  of the capsule  222 , a silver tube  212 ,  213  is provided. Each tube  212 ,  213  is preferably 0.025 inch in length and preferably has a wall thickness of 0.004 inch. The interior surfaces  214 ,  215  and the exterior surfaces  215 ,  217  of the tubes are coated with I-125. As the tubes  212 ,  213  may be shorter than the length of the interior portion  274 ,  276 , a series of spacers  280 ,  220 ,  282  may be provided in the interior portion  274 ,  276  to prevent relative movement of the tubes  212 ,  213  within the capsule  222 . Spacers  280  and  282  may be made of an inexpensive material such as plastic. Spacer  220  is preferably a ceramic spacer in which a radiopaque marker  270  is provided, and over which a titanium ring  221  is provided. Additionally or alternatively, the marker may be diamagnetic. Spacer  220  preferably includes tapered ends  228 ,  230  to facilitate positioning the open ends  242 ,  244  of the two halves  234 ,  236  of the capsule thereover. The two halves  234 ,  236  of the capsule are positioned to abut the ring  221  and are welded (in any manner) to the ring  221  and about the ceramic spacer  220 . 
     A first alternative fourth embodiment of the invention is seen in FIG. 4 a , where therapeutic seed  310   a  is shown. The seed  310   a  includes a preferably titanium capsule  322   a  defined by two halves  334   a ,  336   a , each having a closed end  338   a ,  340   a , an open end  342   a ,  344   a , and an interior portion  374   a ,  376   a . In the interior portion  374   a ,  376   a  of each half  334   a ,  336   a  of the capsule  322   a , isotope bearing structures  378   a  spaced by a two-piece central ceramic spacer  320   a - 1 ,  320   a - 2  are provided. Preferably, the isotope bearing structures  378   a  are one or more radiolucent particles, preferably made from titanium, aluminum or glass, and preferably spherically shaped. The particles  378   a  are provided with a thin coating of silver over which the isotope  318   a  is provided. The ceramic spacer  320   a - 1 ,  320   a - 2  is a two piece, generally hollow cylindrical spacer which carries a two piece axial radiopaque marker  370   a - 1 ,  370   a - 2  therein. The open end  342   a ,  344   a  of each of the halves  334   a ,  336   a  of the capsule is press fit over a respective spacer half  320   a - 1 ,  320   a - 2  which is carrying a respective marker half  370   a - 1 ,  370   a - 2  therein so that the open ends of the capsule abut each other. The open ends of the capsule may then be welded (in any manner) to each other. The result is a capsule  322   a  which has a substantially uniform wall thickness. 
     A second alternative fourth embodiment of the invention is seen in FIG. 4 b , where therapeutic seed  310   b  is shown. The seed  310   b  includes a preferably titanium capsule  322   b  defined by two halves  334   b ,  336   b , each having a closed end  338   b ,  340   b , an open end  342   b ,  344   b , and an interior portion  374   b ,  376   b . As seen in FIG. 4 b , the walls of the open ends  342   b ,  344   b  are thin relative to the remainder of the capsule walls. In the interior portion  374   b ,  376   b  of each half  334   b ,  336   b  of the capsule  322   b , isotope bearing structures  378   b  spaced by a one-piece central ceramic spacer  320   b  are provided. Preferably, the isotope bearing structures  378   b  are one or more radiolucent particles, preferably made from titanium, aluminum or glass, and preferably spherically shaped. The particles  378   b  are provided with a thin coating of silver over which the isotope  318   b  is provided. The ceramic spacer  320   b  is a one piece, generally hollow cylindrical spacer which carries a one piece axial radiopaque marker  370   b  therein. The seed  310   b  is assembled by press fitting the ceramic spacer  320   b  over the middle of marker  370   b , press fitting capsule half  334   b  over the tapered end  328   b  of the spacer  320   b , and press fitting capsule half  336   b  over the remainder of marker  370   b  such that open end  344   b  of capsule half  336   b extends over open end  342   b  of capsule half  334   b . The open ends of the capsule may then be welded (in any manner) or mechanically swaged to each other. The result is a capsule  322   b  which has a substantially uniform wall thickness. 
     There have been described and illustrated herein several embodiments of a radioactive therapeutic seed. While particular embodiments of the invention have been described, it is not intended that the invention be limited thereto, as it is intended that the invention be as broad in scope as the art will allow and that the specification be read likewise. For example, those skilled in the art will appreciated that certain features of one embodiment may be combined with features of another embodiment to provide yet additional embodiments. In addition, while each capsule is preferably formed from two halves, it will be appreciated that the two parts forming the capsule need not be halves, e.g., one part can be one-third the length of the capsule and the other part can be two-thirds the length of the capsule. Also, while one type of MRI-visible substance has been disclosed, other MRI-visible substances may alternatively be used. Similarly, while two specific ceramics have been disclosed, it will be appreciated that other low-density ceramic materials could be utilized. Likewise, while titanium has been disclosed as the preferred material for the capsule and ring, it will be appreciated that other low-density biocompatible metals could be utilized. Furthermore, while the isotope bearing surface has been disclosed as preferably including both the inner and outer surfaces, it will be appreciated that just the outer surfaces may be used as the isotope bearing surface, though it is believed that the embodiments as described provide the most isotropic radiation distribution. Further yet, while welding has been described as the preferred manner of joining the capsule portions to the ring, it will be appreciated that other manners of sealing such as swaging or providing a shrink-wrap could be utilized. It will therefore be appreciated by those skilled in the art that yet other modifications could be made to the provided invention without deviating from its spirit and scope as so claimed.