CA2238647A1 - Hollow-tube brachytherapy device - Google Patents

Abstract

A novel brachytherapy device is disclosed that is formed from a hollow-tube-shaped seed-substrate, allowing the easy association of the device with suture material. This shape minimizes the chance of migration of implanted seeds due to better attachment to tissue. The distribution of the radioactive material on the exterior surface of the tubular device provides a relatively uniform radiation field around the hollow-tube-shaped brachytherapy seed source.
Brachytherapy devices are disclosed that are inherently radioactive. Also disclosed are devices that can be rendered radioactive by the transmuting effects of neutron irradiation. Brachytherapy devices are disclosed that facilitate medical application and improve safety for patients and medical personnel.

Description

CA 02238647 1998-0~-26 W O 97/19724 PCTfUS96119109 HOLI,O W-'IlJe',E BE~YI~H~ ErY DEVICE
Te~hnic~l Field The invention disclosed herein relates to radioactive impl~ntfi for medical therapeutic purposes, referred to in the art as "radioactive seeds," "seed~," or "sow~." The invention relates to seeds for therapeutic r~tli~tion trç~f~nent. of oncological and other medical ron(lit;on!: More particularly, the invention i8 directed to a novel r~ ts~rtive seed for interstitial imrls~nt.~tion brachytherapy and also for general brachytherapy tr~tm~ntc~ The invention is also directed to methods of making the seeds and methods of using the seeds.
Rn ~ L ~ o~d Art The localized treatment of tumors and other medical conditions by the interstitial imrls~nt~hnn of radioactive materials is a recognized treatrn~nt. modality of long stS,n~in~
R~lioflrtive imrl~nt~ are used to provide r~ ti~n therapy in order to reduce or prevent the growth of tumors that cannot be removed by surgical means. R:~.1i t~ive implants are also used to prevent the growth of microscopic metastatic deposits in lymph nodes that drain the region where a tumor has been removed. Tmrl~ntfi are also used to irradiate the postoperative tumor bed after the tumor is excised. Implantation of r~ r+ive sources di-rectly into solid tumors for the destruction of the tumors is used in a therapy referred to as brachytherapy.
Brachytherapy is also used to prevent the regrowth of tissue in circumstances such as the treatment of arteries for occlusive disease. Brachytherapy is applied, for f~ mrle~ in the treatment of atherosclerosis to inhibit restenosis of blood vessels after balloon-angioplasty or other tre~t~n~nt~ to open occluded or narrowed vessels. These brachytherapy trP~tnnent~ involve a short-term application of extremely radioactive sources. The ~rplir~qtions can be for periods as short as a few minutes. This form of brachytherapy may therefore be contrasted with the tre~t~n~nt. of tumors where lower activity sources are used for longer periods of time that may be measured in hours or days or may involve permanent im~ nts~ti~m Tre~tlnl~nt of medical conditions with the local applic~ti~-n of rs~ ticn by im~ ntP~tirm roncAn~ates the treatment on the ~ c~nt tissue and advantageously minimi7~ the exposure of more distant tissues that it is not desired to irradiate. Direct imrlf3ntslti~m of radioactive sources into tumors often permits the aprlic~tion of larger doses of r~ tion than may otherwise be achieved because the rsl~liAhon is applied directly at the site to be irr~ terl Local application of brachytherapy to non-cancerous conditions also allows the use of more intensive tre~t7nen~. than is possible by other means.
In the prior art, brachytherapy ~ iUUll~eSI~ are generally im~l~ntAd for short periods of time and usually are sources of high radiation intensity. For example, irr~ tinn of body cavities such as the uterus has been achieved by placing radium-226 capsules or cesium-137 CA 02238647 1998-0~-26 capsules in the lumen of the organ. In another example, tumors have been treated by the surgical insertion of radium needles or iridium-192 ribbons into the body of the tumor. In yet other in~qnr-o~ gold-198 or radon-222 have been used as radioactive sources. These isotopes require careful hsln~lling because they emit highly energetic and penetrating r~ tinn that can cause xignific~nt exposure to medical personnel and to the normal tissues of the patient undergoing therapy. Therapy with sources of this type requires that hospitals build ~h;~ d rooms, provide medical personnel with appropriate protection and establish protocols to manage the ra~ tion hazards.
The prior art interstitial bldcllyLllerapy tr~ m~?nt. using needles or ribbons has features that inevitably irradiate normal tissues. For ~ mE~Ie, normal tissue surrounding the tumor is irradiated when a high energy isotope is used even though the r~ fir~n dose falls as the square of the distance from the source. Brachytherapy with devices that utilize radium-226, cesium-137 or iridium-192 is hazardous to both the patient and the medical personnel involved because of the high energy of the radioactive ~?mi~sit~n~ The implanted radioactive objects can only be left in place temporarily; thus the patient must undergo both an implantation and removal ~rocedu~.d. Medical personnel are thus twice e~posed to a rs~ ion hazard.
In prior art brachytherapy that uses long-term or permanent impl~nt?~t.icn, the rfl-lio~rfive device is usually referred to as a "seed." Where the r~ fi~n seed is implanted directly into t_e diseased tissue, this form of therapy is referred to as interstitial brachytherapy. It may be distinguished from intra.,dvi~a~ therapy, where the radiation seed or source is arranged in a suitable applicator to irradiate the walls of a body cavity from the lumen.
Migration of the device away from the site of impl:~n~ti~ln is a problem sometimes encountered with presenl;ly available iodine-125 and palladium-103 perm~nently implanted brachytherapy devices because no means of affirmatively lorali7.ing the device may be available.
The prior art discloses iodine seeds that can be temporarily or permsln~n~ly implF~nted. The iodine seeds disclosed in the prior art consist of the radionuclide adsorbed onto a carrier that is enclosed within a welded metal tube. Seeds of this type are relatively small and usually a large number of them are impl~ntcd in the human body to achieve a therapeutic effect. Individual seeds of this kind described in the prior art also intrinsically produce an inhomogeneous radiation field due to the form of the construction.
The prior art also discloses sources constructed by ~nrlo~ing iridium metal in plastic tubing. These sources are then temporarily impl:intPd into ~l re,c~ihle tissues for time periods of hours or days. These sources must be removed and, as a consequence, their application is limited to readily accessible body sites.

CA 02238647 1998-0~-26 Prior art seeds typically are formed in a manner that differs from isotope to isotope.
The form of the prior art seeds is thus tailored to the particular characteristics of the isotope to be used. Therefore, a particular type of prior art seed provides rQ~ nn only in the narrow range of energies available from the particular isotope used.
Brachytherapy seed sources are disclosed in, for ~Qmpll~, U.S. patent 5,405,165 to Carden, U.S. patent 5,354,257 to Roubin, U.S. patent 5,342,283 to Good, U.S. patent 4,891,165 to Sl7t~QnthiriQn, U.S. patent 4,702,228 to Russell et al, U.S. patent 4,323,055 to Kubiatowicz and U.S. patent 3,351,049 to Lawrence, the disclosures of which are incorporated herein by reference.
The brachytherapy seed source ~ rlosed by Carden rnmpriR~o~s small cylinders or pellets on which palladium-103 compounded with non-radioactive palladium has been applied by electroplating. A-l-lit;nn of palladium to palladium-103 permits electroplating to be achieved and allows adjustment of the total activity of the resulting seed. The pellets are placed inside a titanium tube, both ends of which are sealed. The disclosed invention does not provide means to fix the seed source within the tissues of the patient to ensure that the rQ(liQhnn is correctly delivered. The design of the seed source is such that the source produces an asymmetrical rQ~liQti~n field due to the radioactive material being located only on the pellets. The patent also ~ fln~es the use of end caps to seal the tube and the presence of a radiogrQphi- Qlly detectable marker inside the tube between the pellets.
The patent to Roubin relates to radioactive iridium metal brachytherapy devices positioned at the end of minim:~lly invasive intravascular medical devices for providing rQ-liQtinn treatment in a body cavity. Flexible ~lnngated members are disclosed that can be inserted through cQth~t~rs to reach sites where radiation tre~t~n~nt is desired to be applied that can be reached via vessels of the body.
The patent to Good discloses methods such as :~utl/~ g for applying radioactive metals to solid manufactured elements such as microspheres, wires and ribbons. The disclosed methods are also disclosed to apply ~-o~e1tiv~ layers and identfflcation layers. Also disclosed are the r~filllting solid, multilayered, seamless ~l~m~nts that can be implanted individually or rnmhined in intracavitary application devices.
The patent to Suthanthirian relates to the production of brachytherapy seed sources and discloses a technique for use in the production of such sources. The patent discloses an encapsulation technique employing two or more interfitting sleeves with closed bottom portions. The open end portion of one sleeve is designed to accept the open end portion of a second slightly-smaller-diameter sleeve. The patent discloses the formation of a sealed 3~ source by sliding two sleeves together. Seeds formed by the SllthQntl irian process may have a more uniform r~rliQtinn field than the seed disclosed by Carden. However, the seed CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19109 rl~e~ hy Slltl~ntl~irian provides no means for securely locating the seed in thc tissue of the patient.
The patent to Russell et al. relates to the production of brachytherapy ~eed sources produced by the transmutation of isotopically enriched p~ rlillm-102 to r~ rlillm-103 by neutrons produced by a nuclear reactor. The Russell patent also discloses a tits~nillm seed with sealed ends, similar to that of Carden, co..~ i..F a mnltiplirity of compnn-ont~ A seed produced in this manner is ~o~ d with yielding a less than isotropic r~ tinn field.
The patent to Kllhisltowicz teaches a ~iL~lliulll seed with ends sealed by laser, electron beam or tllngFten inert gas welding. The r~-lio~rtive component of the seed is disclosed to be a silver bar onto which the radioisotope iodine-125 is ~~h~mi~nrbed. Seeds produced in this manner also tend to produce an asymmetric radiation field and provide no means of ~t~rhmPnt. to the site of applir~tinn in the patient.
The patent to I.awrence ~liirl~çs a radioactive seed with a titanium or plastic shell with sealed ends. Seeds are disclosed contAining a variety of cylindrical or pellet components onto which one of the radioisotopes iodine-125, palladium-103, iridium-192 or cesium-131 is incorporated. The structure of the disclosed seeds yields a non-homogeneous r,q~ tion field and provides no means for accurately pofiitic-ning the seed in the tissue that it is desired to irradiate.
Currently available brachytherapy seeds do not easily lend th~m~f~lves to s~ ori:~ti~m with suture material. For ~ mrl~ iodine-125 seeds . ~ n~ly in use are placed inside suture material at the time of manufacture. However, the insertion process is tedious and time consuming and has the potential for significant radiation t~L~O~iU~ to the production personnel involved. Adfliti~tnzllly, because of the natural decay of the radioisotope, the suture material thus produced has a short shelf life. As a second f~mple, the manufacturing process used to produce the palladium-103 seeds that are currently in use results in end-ronFhnes~ of the encapsulation of the seed. The r~p~ s are not placcd inside suture material because the end-rollghn~s~ makes insertion very (lifflcl~lt Rigid rods are produced in present terhnol~-gy by the insertion of seeds into suture material followed by heat treatment to form a rigid rod ~ cntzininF the seed. These rods are difficult to produce, very fragile and sensitive to moisture. The presently available brachytherapy technology requires that most physicians use suture material prf~s~nnhl~d vwith the seeds already inside. Similarly, rigid materials used by surgeons for brachytherapy are pre-manufactured and purchased readymade.
Disclosure o~ Invention The present invention providcs a novel general-use brachytherapy device for the interstitial r~ tl~rapy of m:~liFn int neoplasms or other diseases treatable with rs~ tinn The device of the instant invention comprises a hollow tubular support with a lumcn that is CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19109 open on both ends. The tubular support of the device bears a radioactive layer that is ~nrln.cf~l with a sealing layer to prevent contact between the radioactive material and the tissues and fluids of the patient.
The hollow tubular support of the present invention comprises a hollow-tube-shaped seed-substrate that has internal and ~tqrn~l surfaces. Other embo~lim~nt~ of the instant invention have perforations through the walls of the hollow tube. In embo-lim~nt~ that have perforations through the walls of the tube, the pt lr~ ld~ions may be oriented in any direction.
The various ~l~mf~nt~ of the device may be made of titanium or other biocompatible metal or may be made of synthetic material such as plastic.
The radioactive source material is disposed as a layer on the ~~r+Prn~l surface of the tube of the device. Other materials, such as radiogr~phif ~lly ll~tect~hle material, may also be layered on the external surface of the tube of the device. The entire device is provided with a biologically-cnmr?tihle, radiation-permeable, surface-sealing layer that entirely seals the external surface of the tube.
1~ An object of the invention ~ ksell herein is to provide for the improved treatment of medical conditions such as neoplastic ~ e~ s according to the normal practice of brachytherapy, e.g., the interstitial imrls~nt,atinn of radioactive sources into tumorous tissue for the purpose of irr~ ng and thus killing m~lign~nt cells.
An object of the invention (li~-lo~ed herein is to provide a brachytherapy device specifically intDnlle-1 to ease the task of surgeons, urologists, r~ tion therapists, r~-1iologiF~c and others who use brachytherapy devices in providing tre~tm~nt. to p:~tiqntf:
The hollow tubular design promotes simple and .omri~nt. interaction between the device and suture materials c~mmnnly used in surgery. Simply stated, the hollow-tube-shaped form of the device rli~rlosed herein permits suture material, rigid rods or other hiocr m~R~hle (~nn~ ing members to be passed through it in such a way as to fix its position relative to the treatment volume. The suture material, rigid rod or other bi- c--mp~tihle connecting member may be threaded through the device at the time of surgery and can also serve to locate the device relative to other similar devices. This flexibility allows a surgeon to effectively react to challenges not revealed by the pre-surgical work-up of the patient.
The design of the invention disclosed herein promotes simple and efficient interaction between the device and suture materials commonly used in surgery. Thus, the brachytherapy device disclosed herein has special application to the form of brachytherapy wherein seeds are associated with flexible suture material and are thereby held in a crlmpli~nt. array in the neoplastic tissue by the suture while their ra-li?ti-)n dose is del*ered.
This greatly speeds and ~impli~;es the process of applying the brachytherapy device, greatly improves the accuracy of ~mplz~r~m~nt in the tumor and reduces the hazard to which medical personnel are exposed.

CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19109 The hollow-tube feature of the invention ~ rlos~l herein also has special application to the form of brachytherapy in which seeds are associated with a rigid, biocompatible material which holds the seeds in a fixed array in the neoplastic tissue while their r~ tion dose is delivered. In a similar manner to that described above the disclosed device may be 6 simply threaded onto any cnmm-mly used rigid support material to yield a suitable array.
For example a hollow-tube brachytherapy device as disclosed herein may be applied by threading a surgical stainless-steel wire or plastic surgical filament through the lumen. The threaded material may then be used to fix the device to the r~tl~t~r~ The r~th~ter is then used to position the array at a site where brachytherapy is needed.
The most ~,r~lled overall ~im~nqif~nq of the device disclosed herein may be a m~tl~r of ~ .Jxi...s~t~ly 0.8 mm and a length of ~ ..x;~ tely 4.5 mm. The advantage of providing a seed in these ~limen~i~mq is that the device of the present invention may be implanted using currently available instruments. Thus, the need for retooling by the therapist may be avoided, and a brachytherapy device that incorporates the seed-substrate of the instant invention may be applied without mo(lifir~tion of current surgical practices.
Alternatively, the (lim~nqion.q of the seed-substrate may be different from those disclosed above, depf~n-ling upon the specific use to which the device is to be put. Such different 1im~n~innq will be apparent to those of skill in the art.
The devices disclosed herein are ~le~i~ned to deliver a therapeutic dose of r~ t;-n to a spatially well defined and limited volume of diseased tissue within a living body. Such a device is shaped as a hollow tube so that a suture material, rigid rod or other bioçomp~t;hlf~
rnnnf~cting member passed through it can be used to f~ its position relative to other similar devices. The threaded crnn~ctin~ member can also serve to locate the device relative to the treatment volume.
The hollow-tube design of the device of the present invention also permits the growth of tissue into the device. This tissue growth acts to ançhor the device at the application ~iite and minimi7-~ the potential for migration. In embo~imf~nt~ of the device provided with perforations, the perforations also provide additional access for body fluids and tissues to the space inside the tube.
Another object of the invention disclosed herein is to provide an embodiment of the device that has its central tube-shaped substrate formed from a material that is essentially transparent to the radiation emitted by the therapeutic isotope. Such material may be titanium, carbon, st~inlf~R~-steel, tantalum, hafnium or zirconium. The central tube may also be formed from plastics such as polypropylene, polyethylene tereph~h~lP.t.e; nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene sulfide, phenyletheretherketone, polyetherimide or liquid crystal polymer.

CA 02238647 l998-0~-26 The r~lio~rtive m~t~ri~l of the embodiments of the invention of the ~ rlo~f~d herein is coated on the outer surface of the hollow-tube-shaped 6eed-substrate and is ~lvl~ed by the sealing layer. Suitable radioisotopes are palladium-103 or iodine-125. Other isotopes that emit r~ t;~n with the desired therapeutic properties can also be deposited over the outer surface of the tube in a u~liru~ manner, for example gold-198, yttrium-90 and phosphorus-32. The radioactive material in this layer may already be radioactive when it is applied such as by the application of palladium-103 or iodine-125, or it may be applied as a <,UlDI)~ isotope such as gold-197, y~l,rium-89, iridium-191 or palladium-102 that can be applied and then transmuted in situ, as disclosed in more detail below.
In yet another embodiment of the instant invention a non-r~-lio~ive pre-seed is rlose~ In this embodiment the layer of the device that will be rs~ ff-~n-~n~it+in~ may be prepared by first plating the hollow-tube-shaped seed-substrate with a suitable non-rs-lio?~r~;ve isotope that may be transmuted in situ to the desired r~ .t;~n-emitting isotope by bombardment with neutrons. The material in this layer may be a precursor isotope such as gold-197, yttrium-89, iridium-191 or palladium-102. Upon neutron irra~ tion gold-197 is transmuted to "gold-198" (which is actually a mixture of gold-198 and gold-199) with a half-life of 2.7 days and with rP.~ t;on-emitting properties suitable for brachytherapy. For F:innplil~ity this isotope produced by this transmutation is rerelled to hereinafter as "gold-198". Sirnilar processes or transmutation can be used to produce yttrium-g0 from yttrium-98 or palladium-103 from palladium-102.
A particular advantage of this technique is that the time and intensity of the neutron irrs~ ;nn can be adjusted to achieve a particular desired level of activity in the finic;h~d device. The technique of neutron irradiation takes advantage of the fact that titanium and some other low-atomic-number metals have small nuclear cross-sections and are essentially llns~ff~cte~l by neutron irrz~ t~ n A further advantage of this embodiment of the invention is that no radioactive material is used in the actual manufacturing of the device. A third advantage is that manufactured devices may be stored in-l~finitely and may be rendered r~1io~;ve when needed by exposure to neutron irr~ ;nn from a nuclearreactor or cyclotron or other suitable source.
I~l such an embodiment of the invention, the transmutable non-radioactive isotope is first plated onto the hollow-tube-shaped seed-substrate. Second, the plated hollow-tube seed-substrate is inserted into a closely fitting outer tube of the same length, or slightly longer if the outer tube is to be swaged, that provides the sealing layer. This outer tube can be a metal such as titanium, and is made so that this sealing member or outer tube, fits snugly over the inner tube coated with the r~rlioi~otope and radiogr~phi~ :~lly detectable band (if present). The ends of the inner and outer tubes are swaged together and joined, for example by laser welding, so as to form a sealed device. The sealed device thus formed has CA 02238647 l998-05-26 the form of a double-walled tube. The sealing layer may also be for}ned from st~inlf~ -steel, tantalum, hafnium or ~ ,niu~
Alternatively, the outer tube can also be a synthetic material, such as one of the plastics mentioned above, made so that this sealing member or outer tube fits snugly over the inner tube coated with the radioisotope and radiogr~rhi~ y--letectohle band (if present).
In the case of a plastic sealing member the ends of the inner and outer tubes can be sealed by standard techniques like gluing, heat sealing, solvent bonding or ultrasonic welding.
In yet another embodiment of the sealing layer of a material that is essentiallytransparent to the r~ ti-,n,~ emitted by the th~ p,t:u~ic isotope is deposited upon the surface. For f~ mrle, the sealing layer may be made of a material such as pyrolytic carbon deposited from a f~hflmic~l vapor or such as titanium deposited from an atomic vapor. The sealing layer may also be formed from carbon, tantalum, hafnium or zirconium, or may be formed from ~ ni~ll.. carbide, titanium nitride, ~ita,liulll carbonitride, hafnium nitride, or zirconium nitride.
Alternatively, in another embodiment of the invention ~ rlo~f7~1 herein the sealing layer may consist essentially of an organic coating, as for f~ mplf- an organic coating formed from a heat-shrinkable plastic, a coating produced by solvent evaporation, a coating produced by a chemical polymerization reaction or a coating formed by mollling plastic around the device. Such organic coatings may be poly~ ylene, polyethylene terephth~ te, nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene sulfide, phenyletheretherketone, polyetherimide or liquid crystal polymer.
Another feature of the invention lli.crlr"~f d herein provides advantages in situations in which a remote afterloading technique is used. For P~7~mplf~, remote afterloading may be used with implants that are temporary impl~nt~ in the brain. The form of the brachytherapy device disclosed herein offers advantages because isotopes incorporated into these sources (p~ rlillm 103 or iodine-125) emit X-rays of average energy between 21 and 30 keV. A consequence of this low energy is to greatly simplify ~hif llling. For example, the half-value thickness (the ~hi~knf~ of lead le4uiL.3d to reduce the dose rate from a source to 50%) is only 0.006 mm for p~ flinm-103 and 0.02 mm for iodine-125.
Because the devices disclosed herein are simple to shield, most of the features normally associated with brachytherapy techniques that involve remote afterloading are not applicable. Use of the devices disclosed herein would generally not require remote transfer of the radiation source from a ~hif l-lf~d r ~ntAinf r into the tube implanted in the patient.
Similarly, the nf~c~Rity to isolate the patient in a shielded room during treatment is generally avoided with the disclosed devices. Isotopes incorporated into other embo-liment~
of the device emit beta-particles rather than electromagnetic r~ ti~ n~. These beta-particle CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/1910 ~mitf;ng embodiments are advantageous in that they may also be t~e.iiv~ly ~hie~ d by much smaller ~omhin~T;nn~ of plastic and lead than those required by previously available afterloader sources.
Lo~ t;~m of sources following impl~nt~t;nn is of importance because accurate 5 knowledge of the position and ori~?nt~t;on of the sources can confirm that they are in the positions specified in the medical tre~tm~nt plan and consequently will provide a properly distributed rA(li~t;on dose within the tre~t~n~nt volume. To provide means whereby the device can be located after im~ nt~t;~m, one embodiment of the present invention is formed with radiogr~ph~ lly opaque material such as gold, platinum or other ap~ ;ate high-atomic-number element deposited on the device~ preferably as a band on the surface near the center of the device. This radiopaque material allows the visn?li7:~t;~n of the implanted device by standard radiographic proce.lules and allows the location and ori~nt~tinn to be accurately determined during tr~tTnent When the radioactive material is applied to an embodiment of the invention that bears a band of radiographically detect~hl.q material, the radioactive material may extend over the band of radiogr~phi- ~lly ~ tert~hle material. In another embodiment the rs~ ctive material may extend only to within appl.~x i ~ t~ly 0.5 mm of the end edge of the tube-shaped seed-substrate and thus provide a narrow nonradioactive ring at each end of the device. Generally, the radioactive material may be disposed on the device to suit many purposes that will be obvious to those of skill in the art.
In pfarel.ed embodiment~ of the present invention, a biocompatible sealing layer is deposited so that the entire external surfaces of the device are composed of a biocom~:lt. hl~
m~t.ori~l The sealing layer prevents radioactive materials from escaping and provides a r~-liosl- tive device which meets the normal d~finit.inn of a ''sealed source." The sealing layer is made of a plastic material or any other biocompatible material, provided the material is adequately transparent to the therapeutic r~ t.i--n and has sufficient durability to protect and retain the radioisotope underneath. In another embodiment the sealing layer can be made of ~ lliUlll or other suitable biocompatible metal that is adequately transparent to the therapeutic r~ t; f)n The device disclosed herein will be used for the treatment of medical con~lit;on~ such as neoplastic rli.~es3~ according to the normal practice of brachytherapy, e.g., the interstitial implantation of r~-lioactive sources into tumorous tissue for the purpose of irr~ ting and thus killing m~lign~nt. cells. Other uses are the ~mpl:~rf?m~nt into vessels of the body, e.g., to inhibit restenosis of blood vessels.
Brief Dcs~ ,ion of the Drawings Figure la shows a diagr:~lmm~ti~ repr~ nt~tion of a cross section of a device of the instant invention that is formed with a plastic sealing layer.

CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19109 Figure lb shows a diagr~mmAti~ representation of a cross section of the end of the device shown in Figure la to reveal details of the interaction of the plastic sealing layer and the tube-shaped seed-substrate.
Figure 2a shows a diagrammatic fe~dselltation of a cross section of an alternative device of the instant invention formed with a electroplated sealing layer.
Figure 2b shows a diagr~mm~ti- repr~nt.~tinn of a cross section of the end of the device shown in Figure 2a to reveal details of the interaction of the electroplated sealing layer and the tube-shaped seed-substrate.
Figure 3a shows a diagrammatic reprf~q.qnt~t;~m of a cross section of yet another device of the instant invention formed with an outer tube sealing layer.
Figure 3b shows a diagr~mm~tir repr~.c-~nt~+i--n of a cross section of the end of the device shown in Figure 3a formed with an outer tube sealing layer to reveal details of the swaged and welded joint.
Figure 4 shows a perspective repr~.q-ont.~t.i~n of devices of the instant invention disposed upon a surgical suture.
Figure 5 disposed shows a perspective reprf~.qnt~ti~m of devices of the instant invention disposed on a rigid surgiQl support.
Modes for Carrying Out the Inve~tion An embodiment of the device disclosed herein that has a radiogrSIphic~lly detectable band provides means whereby the device can be located after implantation. Thus, embo~lim~nts of the present invention may be formed with a band of a radiogr~rh ~l~tect~hle material such as gold, platinum or another appropriate high-atomic-number element deposited near the center on the external surface of the hollow-tube-shaped seed-substrate. This band allows the vis~ t;on of the implanted device by standard radiographic procedures and allows the location and ori~nt.~til-n to be accurately determined during t,r~t~n~nt. or in advance of surgery. The radiographically detect~hl~ band may be applied to entirely encircle the external surface of the hollow-tube-shapcd seed-substrate at right-angles to the longitudinal axis of the seed. The band may be 1.2 mm wide and be centrally positioned to allow accurate detern~in:~ti-ln of the position of the seed by standard radiographic, fluoroscopic or co~ u~L-tomography visn~ ti~n. The band of radio~ tectqhlf? material such as gold, pl~tinllm or another appropriate high-atomic-number el~?m(?nt may be deposited by means similar to those described below for deposition of the r~ tive source material.
In manufacturing one embodiment of the invention disclosed herein, a therapeuticradioisotope is deposited on the outward-facing surface of the hollow-tube-shaped seed-substrate in such a manner as to produce an .o~enti~lly uniform cylindrical radiation field in close ~lO~ y to the device. The radioactive layer is then covered by a sealing layer, the CA 02238647 1998-0~-26 W O 97/19724 PCTAJS96/19lO9 purpose of which is to prevent the escape of a ~ign;fi~nt amount of the radioactive material into the surrounding living body.
The disposition of the radioactive source layer on the external surface of the hollow-tube-shaped seed-substrate may be varied to achieve different ends. As example, the r~-lio~c+ive source layer may extend over the entire external surface of the hollow-tube-shaped seed-substrate and extend over a previously- applied radiogr~phir~lly detectable band. In an alternative embodiment the radioactive source layer may be e~cluded from a region at each end of the external surface of the hollow-tube-shaped seed-substrate in order to provide a narrow non-radioactive ring at each end of the seed. In a further embodiment, the r~r1it~r~ive source layer may extend over the entire external surface of the hollow-tube-shaped seed-substrate with the e~ception of the region that bears the radiographically detect~hl~ band.
An embodiment of the invention disclosed herein may have the central hollow-tube-shaped seed-substrate formed from a material ~ nti~lly transparent to the rç~ n emitted by the therapeutic isotope. Such materials may be ~l~m~nt.~ such as titanium, carbon, tantalum, hafnium or zirconium or an alloy such as stainless-steel. Alternatively, organic polymers may be used for fabrication of the hollow-tube-shaped seed-substrate and may be any of a number of materials such as poly~ ylene, polyethylene terephtl~late, nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene su}fide, phenyletheretherketone, polyetherimide or liquid crystal polymers. Such polymers and their sources are ~ rlosed in Table 1.
A further feature of embo-liment.~ of the invention is that the radioactive layer is covered by a sealing layer, the purpose of which is to prevent contact with the radioactive isotope and to prevent the escape of radioactive material into the surrounding living body.
~5 The sealing layer may be a material essentially transparent to the radiation emitted by the therapeutic isotope, such as pyrolytic carbon deposited from a chemical vapor. An alternative sealing layer such aH titanium may be deposited from an atomic vapor. A
further embodiment of the sealing layer may comprise an organic coating, as for ~ mple a coating formed from a heat shrinkablLe plastic, a coating produced by solvent evaporation, a 3~ coating produced by a polymerization reaction or by molding plastic around the exterior of the device.
An optional feature of the invention disclosed herein is to provide a radiogrslphirzllly letect~hle band, desirably applied near the median point of the long axis of the device with snffirient. width and opacity to make the device visible and its orientation apparent on a 3~ radiograph taken of a patient following implantation of the device.

TA~BI~E 1: ACCEPTA~BI~E NON~BSOR~BI~E PO~YDIEE~SYVII~E T~IEDR T~DE
NA~ES A~D Conrtr~Rc~AL SOlnRCES

Material Trade Names Source~
Polyurethane Texin, Desmopan, Estane Bayer Corp., B F C~oodr~ch Poly~lv~-ylene Surgilene, Prolene ~t~icon~
American Cyanamid Polyethylene terepht~ t~ Impet, Petra, Rynite, Estar Allied, Hoechst, Celanese, (PET) duPont, Eastman Polyphenylene oxide blends Noryl, Prevex General Electric (PPO) Polyphenyl~ulfi-n~ (PPSU) Radel R Amoco Polysulfone ~PSU) Udel, Ultrason S Amoco, BASF
Polyether sulfone (PES) Radel A, Ultrason E Amoco, BASF
Polyphenylene sulfide (PPS) Fortron, Ryton, Supec Hoechst, Celanese, Phillips, GE
Phenyletheretherketone Kadel, Victrex Amoco, Victrex (PEEK) Polyetherimide (PEI) Ultem GE
Nylon Nylon duPont Liquid crystal polymer (LCP) Vectra ~oerh~t, Celanese The lumen of the hollow-tube-shaped seed-substrate comprises a sllhs~5lntis-l proportion of the total diameter of the device. In a ~l~r~lled embodiment, the total wall tl~irkn~ of the seed including the inner tube substrate, radioisotope source material layer, radiographically-detectçlhl~ band if present and sealing layer is a~ xi...~t~ly 0.15 mm, and the lumen ~ met~r is a~.. xi~ t~ly 0.51 mm, large enough to admit the passage through it of suturing needles and sutures.
In other embo(liment~ of the instant invention, the wall of the hollow-tube-shaped seed-substrate may be pierced transversely by one or more perforations. In embo-liment~
that have perforations through the wall of the tube, the perforations may be shaped and oriented in any direction in order to best serve the purposes disclosed below. In embodiments of the device that are provided with p~lrolaLions, the perforations provide access for body fluids to the lumen of the tube. Perforations in the wall of the tube may also provide anchor point~ as tissue grows into the holes. Perforations may desirably be in the ' range of 0.031 to 0.31 mm wide.
The hollow-tube-shaped seed-:iubbLldL~ of the instant invention may be made of titanium or other biocompatible metal or may be made of synthetic material such as plastic.

- =
CA 02238647 1998-0~-26 W O 97/19724 PCTrUS96/19109 Where titanium or other hi~comp~tihl~ metal is used, the tubes may be formed by a standard cold-drawing processes to form metal tubes. For ~ mpl~, hollow-tube-shaped seed-substrates of the instant invention may be made from ASTM B265-78 grade 2 ~it~ninm by forming tubu}ar sections 4.5 mm in length, 0.57 mm in outside diameter and 0.5 mm 5 inside diameter. Such titanium tubes are available commercially in the U.S.A. from the Uniform Tube Company, Collegeville, Pennsylvania 19426.
Where the hollow-tube-shaped seed-substrate of the instant invention is made of plastic or synthetic material, the seed-substrate may be formed by extruding or mnl~ling the tube from the mass material in a manner suitable to the material being formed. A number 10 of engineering plastics represent acceptable materials including poly~3lvl~ylene, polyetherimide, polyethylene terephtl~lzte, nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene sulfide, phenyletheretherketone, polyetherimide or liquid crystal polymers. These materials are available from suppliers listed in Table 1. Other polymeric and plastic m~ ri~lc that are suitable for use in the present invention will be obvious to those skilled in art.
The r~-lioP~ ve source material of the instant invention is disposed as a layer on the external surface of the hollow-tube-shaped seed-substrate. The instant invention differs in this respect from prior art brachytherapy devices. In the prior art, brachytherapy devices are generally disclosed in which the radioactive source material is present in association with a pellet or rod contained within an ~nc~I)cl~ ing rh~mhl~r The structure of the instant invention is advantageous in that all components of the source, including the disposition of the radioactive source m:~t~ri~l and a radiogr~phi~lly detectable band, if present, are deposited onto the external surface of the structural member of the seed, the hollow-tube-shaped seed-substrate. The central lumen of the seed-substrate is unobstructed, thus making the hollow design possible with all the subsequent advantages imparted by that design.
Designers of prior art brachytherapy devices made use of internal components such as pellets or rods to provide a support for the radioactive source material of the seed. In some prior art designs, radiogr:~phir~lly-detectable markers were also encapsulated together with the radioactive source material. The use of such internal components in prior art designs re~uires an encapsulating chamber and precludes a hollow-tube-shaped seed design.
The radioactive source layer is applied to the hollow-tube-shaped seed-substrate by any of a variety of convf~nt.inn~l process such as sputtering, laser :~hl~ti~)n, ~ hn~ arc plasma deposition, curvilinear ç~tho(li~ arc plasma deposition, vapor deposition, or electroplating. Such known processes are further set forth in U.S. patent 5,342,238 to Good, the ~ re of which is hereby incorporated by reference.

CA 02238647 1998-0~-26 WO 97/19724 PCT~US96/19109 For example, but not by way of limit~ n, the radioactive layer on the hollow-tube-Hhaped seed-substrate may be electroplated onto the external surface of the hollow-tube-shaped seed-substrate. The exact method for applir~ n of the layer depends upon the material to be d~po ~ d and the material of which the tube is constructed. If the tube is constructed from a material which does not conduct electricity, such as a pla~tic, the outer surface must first be metnlli7:ed to make it conducting. This may be achieved by any one of several standard techniques commonly used in the plastics industry. If the tube is constructed from a material difficult to electroplate, such as titanium, a surface pretrf~qt~n~nt. is re4uiled to obtain reliably-adherent electrodeposition of plating layers.
For ~mple, a surface pretreatment procedure for t;t~ninm has been disclosed by Pratt Whitney Aviation that includes an abrasive blast, a hot ~Ik:~lin~ rle~n.~inF in 30%
pot~inm hydroxide, a hydrochloric acid pickle, a "bright dip" (achieved by dipping in an aqueous solution of 12% by volume acetic acid, 70% hydrofluoric acid and 1% nitric acid), an "anodic etch" for 6 mirlutes at 162 amperes per square meter (achieved in 13% by volume hydrofluoric acid, 83% acetic acid and 4% water), a "sulfate nickel strike" to an a~ ,xi~ te thirkn~ of 25 microinches followed by drying in air for 2 hours at 48 degrees C. This process achieves deposition of a thin nickel layer onto the surface of the titanium, thus providing a more advantageous surface layer for electroplating.
If desired, a radiogr~rl~ir~lly detect~hle band, for example a band of gold a~ xi~ t~ly 0.01 mm thick by 1.2 mm wide, deposited from a commercial electroplating solution (for R~mrl~? AuRoTechP1 from AT&T Electroplating Ch~mir~l~ and Services) can be deposited directly onto a previously-applied thin nickel layer applied as described above.
Embo~lim~nt~ of the instant invention may incorporate different therapeutic isotopes in order to achieve different therapeutic purposes and to achieve different activities. For example, beta-particle emitting isotopes such as yttrium-90 and phosphorus-32 may be prepared with total activities of from 0.1 to 100 millicuries. Beta-emitting devices are slntiripat~d to be used for therapy where relatively little penetration of the rs~lio:7ctivity is desired. In other f~mho~lim~nt~ isotopes that emit electromagnetic r~ ion are used. Such embodiments may have activities as high as 10 curies and are used in applir,~tinn~ such as short-term applir~tion~ of only a few minntP~ to prevent or inhibit the r~?st~nl)ci~ of blood vessels after angioplasty.
If the therapeutic radioisotope is palladium-103, the radioactive source material layer may be deposited onto the hollow-tube-shaped seed-substrate by the method disclosed in U.S. patent 5,405,309 to Carden, the disclosure of which is hereby incorporated by reference. This electroplating i.orhnnlngy can provide apparent activities of from 0.1 to 300 millicuries per seed.

CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19lO9 If the therapeutic radioisotope to be used iB iodine-125, a uniform layer of silver is first deposited onto the outer surface of the hollow-tube-shaped seed-substrate. Any of the techniques cited above can be used for this purpose provided a uniform and adherent layer of a~pl.)xi..-~t~ly 0.025 mm +~irkn~c~ results. The iodine-125 is then chemisorbed onto the silver layer by the method (li~cln~ed in U.S. patent 4,323,055 to Knhi~tclwicz, the disclosure of which is hereby incorporated by reference. This ~ edule can provide apparent seed activities of from 0.1 to 100 millicuries per seed.
The radioactive material layer may be deposited in a radioactive form such as the applir~ m of palladium-103, iodine-125 or yttrium-90. Alternatively, a precursor isotope such as gold-197, yttrium-89, iridium-191 or palladium-102 may be deposited and then transmuted in situ, for example, by bombardment with neutrons, into the desired therapeutic isotope. For example, yttrium-89 may be deposited on the outer surface of the hollow-tube-shaped seed-substrate by electroplating or otherwise depositing the yttrium-89, and yttrium-90 may be produced by bombardment with neutrons to transmute the non-radioactive isotope. Gold-198 (generally referred to by this (l~Rignsltinn, though cnntS~ining gold-199 isotope as well), yttrium-90 and p~ ]m-103 may be produced by analogousprocesses.
The application of brachytherapy sources for the medical therapeutic applir?(tion of radiation requires that the radioactive source be entirely sealed to prevent escape of the radioisotope. This is P.~nti~l to preclude the systemic distribution of the isotope within the patient and cont.~min:~tinn of medical personnel, medical f~riliti~.c and the general environment. In the ~ r~lled embodiments of the instant invention, the entire radioisotope source layer is provided with a biolng~r~lly-rnmr~tih1~, r~ inn-per~e~hle, surface-sealing layer that entirely seals the external surface of the hollow-tube-shaped seed-substrate with the radioactive and radiogr~phir~1ly detectable layers applied thereon. The sealing layer seals to the ends of the hollow-tube-shaped seed-substrate ensuring a hermetic seal. The sealing layer prevents r~-lio:~rtive materials from escaping and provides a radioactive device which meets the normal d~finit;nn of a "sealed source."
In one embodiment the sealing layer may be made of a plastic material or any other biocomr~tihle organic material, provided the material is adequately transparent to the therapeutic rs~ t.ion and has snffiril~nt. durability to protect and retain the radioisotope.
Such a sealing layer v.~ill cover the entire external surface and the layers applied thereon of the hollow-tube-shaped seed-substrate. Such a sealing layer may be made from a heat shrinkable plastic, or from a coating formed by solvent evaporation or polymerization reaction, or by molding plastic around the exterior of the device. The adjacent ends of the outer sealing layer and the hollow-tube seed-substrate are joined by the process of applying the sealing layer.

CA 02238647 1998-0=.-26 W O 97/19724 PCTnUS96/191~9 In another embodiment the sealing layer may be made of a plastic material or anyother biocompatible organic material, provided the material is adequately transparent to the therapeutic r~ ti~.n and has snffiri~nt durability to protect and retain the radioisotope.
Such a sealing layer will have the form of an outer tube that covers the entire external surface and the layers applied thereon of the hollow-tube-shaped seed-substrate. Such a sealing layer may be made from any of a number of plastics shown in Table 1. The ~ r~nt.
ends of the outer sealing tube and the hollow-tube seed-substrate may be joined by one of several processes. For example they may be joined by gluing, heat sealing, ultrasonic welding or solvent welding.
Manufactured devices are tested for physical integrity and leakage, following the appropriate standard as for ~m~ 7 ANSI-44.2 1973, ANSI-542 1977 and/or IS0-2919.These test standards ensure that devices comply with the requirements to be defined as sealed sources by testing for physical integrity and leakage.
In another embodiment the sealing layer can be made of tit~nillnn, hafnium or zirconium metal or other suitable hinc-~np~tihl~ metal that is adequately transparent to the th~lap~uLic radiation. Such a sealing layer will seal to the ends of the hollow-tube-shaped seed-substrate and cover the entire external surface and the layers applied thereon of the hollow-tube-shaped seed-substrate. This sealing layer may be applied as a hollow tube which is swaged and bonded on each end of the hollow tube seed substrate. In an alternative embodiment, the sealing layer may be applied as a layer of metal deposited by any of the means cited above to form the radioactive layer.
In yet another embodiment the sealing layer can be made of a layer of titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, or zirconium nitride as disclosed by Good, or be made of another suitable biocompatible metal or metal compound

2~ that is adequately transparent to the therapeutic ra~i~t.ion ~uch a sealing layer will cover the entire external surface and the layers applied thereon and seal to the ends of the hollow-tube-shaped seed-substrate or the internal surface of the hollow-tube-shaped seed-substrate in a manner that suffices to meet the objectives of the instant invention.
A detailed description of a particular embodiment of the instant invention is made by reference to Figure la and lb. The embodiment of the instant invention disclosed in Figure la comprises a novel brachytherapy seed-substrate that has the form of a hollow tube open on both ends and having an internal surface 102 and external surface 103. The hollow-tube-shaped seed-substrate 101 of the device 100 may be made of titanium or other biocompatible metal or may be made of synthetic material such as plastic. The radioactive

3~ source material 104 is disposed as a uniform layer on the external surface 103 of the device.
The ra-lios~c~ive layer 104 thus has the form of a cylinder disposed upon the external surface 103 of the hollow-tube-shaped seed-substrate 101. A radiographically detectable layer 105 is CA 02238647 1998-0~-26 W O 97/19724 PCT~US96/19109 shown layered on a portion of the external surface 103 of the hollow-tube-shaped seed-substrate. The radiogr~rhit~lly detectable layer 105 is thus similarly in the form of a cylinder on the external surface 103 of the hollow-tube-shaped seed-substrate 101 disposed at right-angles to the long axis of the seed-substrate. The entire device 100 is provided with a hi-~lngi-~ illy-cnmr~tihle, radiation-permeable, surface-sealing layer 106 that entirely covers and seals the radioact*e layer 104, the radiogr~phi( ~lly detectable layer 105 and the ends of the hollow-tube-shaped seed device. The biologically-compatible, ra~ fi~ n-permeable, surface-sealing layer 106 is applied by a process such as shrink-w,dppillg and forms a seal 107 to the hollow-tube-shaped seed-substrate 101. The lumen of the device 108 is shown.
Figure lb shows the details of the hollow-tube-shaped seed-substrate 101 open at an end and having an internal surface 102 and an external surface 103. The radioactive layer 104 is shown as a uniform layer on the ~t~rn:~l surface 103 of the device 100. The device 100 is provided with a hiologi(~lly-compatible, ra~ ti~n-permeable, surface-sealing layer 106 that entirely covers and seals the radioactive layer 104 and the end of the device 100.
The biologically-c- mp~tihle, r~ ti~)n-permeable, surface-sealing layer 106 is applied by a process such as shrink-wrapping and forms a seal 107 to the tube-shaped seed-substrate 101. The lumen of the device 108 is shown.
Figures 2a and 2b show a diagr~mm~til~ repres~nts~t.inn of a cross-section of anembodiment of the instant invention that is formed with a perforation 209 through the wall of the device 200 and is sealed with an electroplated sealing layer 206. The cross-section shows a portion of the hollow-tube-shaped seed-substrate 201 and its intF~rnz~l surface 202 and its external surface 203. The diagram shows the location of the rP.~ tive layer 204 upon the external surface 203 of the hollow-tube-shaped seed-substrate 210 and the radiogr~phic~lly detectable layer 205 also disposed upon the external surface 203 of the hollow-tube-shaped seed-substrate 201. The radioactive layer 204 is excluded from the terminal portion 207 of the external surface 203 of the hollow-tube-shaped seed-substrate 201. The diagram shows the sealing-layer 206 covering the r~ ve layer 204, the radiogr~rhi- ~lly detectable layer 205 and the external surface 203 of the hollow-tube-shaped seed-substrate 201. The seal 207 between the electroplated sealing layer 206 and the end 210 of the hollow-tube-shaped seed-substrate 201 is shown.
Figure 2b shows a diagr~mm~ti~. reprf~nt~tion of the detail of a cross-section of an end of a device 200 of the instant invention that is formed with a electroplated sealing layer 206. The cross-section shows a portion of the hollow-tube-shaped seed-substrate 201 and its internal surface 202 and its external surface 203. The diagram shows the location of the radioactive layer 204 upon the external surface 203 of the hollow-tube-shaped seed-substrate 201. The diagram shows the sealing-layer 206 covering the radioactive layer 204. The end 207 of the hollow-tube-shaped seed-substrate 201 from which the radioactive layer 204 is CA 02238647 1998-0~-26 W O 97/19724 PCTnJS96/19lO9 f~Y~ ed is shown, together with the seal 210 between the sealing layer 206 and the end 207 of the hollow-tube-shaped seed-substrate 201.
A novel feature of an embodiment of the brachytherapy device disclosed herein is the external tube that is swaged and laser welded to the hollow-tube-shaped seed-substrate shown in Figures 3a and 3b. In Figure 3a a diagr~mm~ cross section of a completehollow-tube device 300 with an external sealing tube 311L is shown. The cross-section shows the hollow-tube-shaped seed-substrate S01, its internal suRace 302 and its external suRace 303. The diagram shows the location of the r~ ~;ve layer 304 upon the external suRace 303, the location of the hollow-tube-shaped seed-substrate 301 and that of the radiogr~phir~lly detRct~hlR layer 305 also disposed upon the external surface 303 of the hollow-tube device 300. The diagram shows the outer sealing-layer 311 Rnrlo~ing the radioactive layer 304 and the radiogr~rhi- ~lly detectable layer 305. The end of the hollow-tube device 300 showing the swaged region 312 and laser-welded region 313 is shown.
Figure 3b is a diagrslmm~h~ le~les~lltation of a cross-section of the swaged and laser welded end of double-walled tube device shown in Figure 3a. The cross-section shows the end of the tube-shaped seed-substrate 301 and its internal suRace 302 and its external suRace 303. The diagram also shows the location of the radioactive layer 304 upon the external surface 303 of the hollow-tube-shaped seed-substrate 301. The outer sealing-layer 311 is shown ~nt~lo.cing the radioactive layer 304. The swaged region 312 and the laser-welded region 312 at the end of the sealed device is shown.
A particular utility of the hollow-tube-shaped brachytherapy device disclosed herein is its ability to be surgically sewn into position by sutures or rigid elements passed through the lumen of the device. Figure 4 shows a perspective representation of a device 401 and a portion of a second device 402 of this invention disposed on a suture 403.
Figure 5 shows a view of a device of this invention 604 shown disposed on a rigid surgical support 505 as the device would be used in practice.

Claims (58)

Claims What is claimed is:

1. A double-walled tubular brachytherapy device for interstitial implantation of radiation-emitting material within a living body, said double-walled tubular brachytherapy device comprising:
an inner tubular element and an outer tubular element, said inner tubular element and said outer tubular element each having a first end and a second end, said inner tubular element and said outer tubular element being of a substantially equal length and said inner tubular element being substantially centrally disposed within said outer tubular element and spaced apart therefrom, said first ends being sealingly joined and said second ends being sealingly joined; and wherein said inner tubular element comprises a tubular support having a lumen therethrough, an internal surface, and an external surface, said external surface having radiation-emitting material thereon.

2. The double-walled tubular brachytherapy device of claim 1, wherein said innertubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium and zirconium.

3. The double-walled tubular brachytherapy device of claim 2, wherein said radiation-emitting material comprises a material selected from the group consisting of:
palladium-103, iridium-192, iodine-125, gold-198, yttrium-90 and phosphorus-32.

4. The double-walled tubular brachytherapy device of claim 3, wherein said radiation-emitting material is a quantity of radiation-emitting material having an activity of between 0.1 and 10,000 millicurie.

6. The double-walled tubular brachytherapy device of claim 4, wherein said radiation-emitting material is an essentially uniform layer of radiation-emitting material.

6. The double-walled tubular brachytherapy device of claim 1, wherein said outer tubular element comprises a material essentially transparent to the radiations emitted by said radiation-emitting material.

7. The double-walled tubular brachytherapy device of claim 6, wherein said outer tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium, zirconium, titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, and zirconium nitride.

8. The double-walled tubular brachytherapy device of claim 7, wherein:
said first open end of said inner tubular element is sealingly joined to said first open end of said outer tubular element; and said second open end of said inner tubular element is sealingly joined to said second open end of said outer tubular element;
wherein said ends are sealingly joined by swaging said ends together and said ends are further joined by laser welding so as to form a sealed device.

9. The double-walled tubular brachytherapy device of claim 1, additionally comprising:
material detectable by radiography disposed as a band on said external surface, said band being essentially centrally located relative to the long axis of said double-walled tubular brachytherapy device, said band having sufficient width and radiopacity to make said double-walled tubular brachytherapy device detectable and its orientation determinable by radiographic examination;
whereby the presence and orientation of the double-walled tubular brachytherapy device may be determined by radiographic examination in a patient receiving brachytherapy with the double-walled tubular brachytherapy device.

10. The double-walled tubular brachytherapy device of claim 9, wherein said inner tubular element comprises a material selected from the group consisting of: polypropylene, polyethylene terephthalate, nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene sulfide, phenyletheretherketone, polyetherimide and liquid crystal polymer.

11. The double-walled tubular brachytherapy device of claim 10, wherein:
said outer tubular element is a material essentially transparent to the radiations emitted by said radiation-emitting material and comprises a plastic selected from the group consisting of: polypropylene, polyethylene terephthalate, nylon, polyurethane, polyphenylene oxide blends, polyphenylsulfone, polysulfone, polyether sulfone, polyphenylene sulfide, phenyletheretherketone, polyetherimide and liquid crystal polymer;
said outer tubular element is fitted over said inner tubular element with said radiographically detectable band deposited thereon and said radiation-emitting material deposited thereon;

said first open end of said inner tubular element and said first open end of said outer tubular element are sealingly joined; and said second open end of said inner tubular element and said second open end of said outer tubular element are sealingly joined;
wherein said ends are sealingly joined by a process selected from the group consisting of:
gluing, heat sealing, ultrasonic welding and solvent welding.

12. A double-walled tubular brachytherapy device of claim 1, wherein:
said inner tubular element has a plurality of perforations;
said outer tubular element has a plurality of perforations;
said outer tubular element is disposed so that said perforations in said outer tubular element are aligned with said perforations of said inner tubular element;
wherein said inner tubular element and said outer tubular element are sealingly engaged, thereby encasing said radiation-emitting material so as to prevent contact between bodily fluids and said radiation-emitting material of said brachytherapy device;whereby said plurality of perforations permit bodily fluids ready access to said lumen of said double-walled tubular brachytherapy device, thereby promoting tissue growth in and around said double-walled tubular brachytherapy device.

13. A double-walled tubular precursor device adapted to be transmuted into a brachytherapy device, said double-walled tubular precursor device comprising:
an inner tubular element having an inner surface, an outer surface, two open ends and a lumen therethrough, said lumen being continuous with said open ends;
a layer of an isotope on said outer surface of said inner tubular element;
wherein said isotope is selected from the group consisting of: gold-197, iridium-191, palladium-102, phosphorus-31 and yttrium-89;
wherein said inner tubular element is disposed coaxially relative to said outer tubular element and spaced apart therefrom; and an outer tubular element sealingly encasing said isotope so as to yield a sealeddouble-walled tubular precursor device.

14. A method for converting a double-walled tubular precursor device of claim 13, into a double-walled tubular brachytherapy device, said method comprising:
irradiating said sealed double-walled tubular precursor device with neutrons so as to transmute said isotope to a radiation-emitting isotope, said neutrons being applied to said double-walled tubular precursor device by a nuclear reactor, or a cyclotron.

15. A method of using a double-walled brachytherapy device having a lumen therethrough, said method comprising:
threadedly inserting through a lumen of a double-walled tubular brachytherapy device a member selected from the group consisting of surgical wire and surgical plastic filament;
fixedly attaching said double-walled tubular brachytherapy device upon said member;
inserting a catheter into a patient at a site where brachytherapy is desired to be delivered by threadedly inserting said catheter through a vessel or by surgically inserting said catheter; and inserting said double-walled tubular brachytherapy device into said catheter by means of said member.

16. The method of claim 15, additionally comprising:
positioning a plurality of double-walled tubular brachytherapy devices, each having a lumen therethrough, on said member by threadedly inserting said member through said lumen of each of said double-walled tubular brachytherapy devices;
whereby said plurality of double-walled tubular brachytherapy devices is inserted into said catheter by means of said member.

17. A method of fixedly-locating during surgery a double-walled tubular brachytherapy device having a lumen therethrough, said method comprising:
threadedly inserting a surgical fixative through a lumen of a double-walled brachytherapy device;
wherein said surgical fixative is suture material or a rigid surgical fixative rod;
selecting a location where brachytherapy is desired to be delivered, said location being relative to the tumor to be treated, relative to the treatment volume to be irradiated, or relative to other brachytherapy devices;
surgically attaching said hollow-tube brachytherapy device in a patient at said location by means of said surgical fixative;
whereby said double-walled tubular brachytherapy device may be fixedly located relative to a tumor, relative to a volume to be irradiated or relative to other brachytherapy devices.

18. The method of claim 17, additionally comprising:
positioning a plurality of double-walled tubular brachytherapy devices, each having a lumen therethrough, on said surgical fixative by threadedly inserting said surgical fixative through said lumen of each of said double-walled tubular brachytherapy devices;

whereby said plurality of double-walled tubular brachytherapy devices is inserted fixedly located relative to a tumor, relative to a volume to be irradiated or relative to other brachytherapy devices.

19. A method of making a double-walled tubular brachytherapy device having a lumen therethrough for interstitial implantation of radiation-emitting material within a living body, said method comprising:
depositing a layer of radiation-emitting material on an external surface of an inner tubular element, said inner tubular element having a first open end, a second open end, and a lumen continuous with said first open end and said second open end;
positioning said inner tubular element within an outer tubular element, said outer tubular element having a first open end, a second open end, and a lumen continuous with said first open end and said second open end, said inner tubular element being of substantially equal length to said outer tubular element, wherein said inner tubular element.
is disposed substantially centrally within said outer tubular element and spaced apart therefrom;
sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element.

20. The method of claim 19, wherein said inner tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium and zirconium.

21. The method of claim 20, wherein said radiation-emitting material comprises amaterial selected from the group consisting of: palladium-103, iridium-192, iodine-125, gold-1953, yttrium-90 and phosphorus-32.

22. The method of claim 21, wherein said radiation-emitting material is a quantity of radiation-emitting material having an activity of between 0.1 and 10,000 millicurie.

23. The method of claim 22, wherein said radiation-emitting material is disposed as an essentially uniform layer of radiation-emitting material.

24. The method of claim 23, wherein said outer tubular element comprises a material essentially transparent to the radiations emitted by said radiation-emitting material.

25. The method of claim 24, wherein said outer tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium, zirconium, titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, and zirconium nitride.

26. The method of claim 22, wherein sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element comprises swaging said ends together, and further sealingly joining said ends by laser welding, so as to form a sealed device.

27. The method of claim 22, wherein said depositing a layer of radioactive material is achieved by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

28. The method of claim 22, additionally comprising:
depositing a radiographically detectable band on a portion of said external surface of said inner tubular element by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

29. A method of making a double-walled tubular brachytherapy device having a lumen therethrough for interstitial implantation of radiation-emitting material within a living body, said method comprising:
fabricating an inner tubular element, said inner tubular element being fabricated to have an external surface, a lumenal surface, a first open end, a second open end, and a lumen continuous with said first open end and said second open end;
fabricating an outer tubular element, said outer tubular element being fabricated to have a first open end, a second open end, and a lumen continuous with said first open end and said second open end, said tubular element also being fabricated to be of substantially equal length to said tubular support and of a diameter sufficient to permit said tubular support to be positioned within said lumen of said tubular element;
depositing a layer of radiation-emitting material on said external surface of said inner tubular element;

positioning said inner tubular element within said outer tubular element so that said inner tubular element is disposed coaxially and substantially centrally within said outer tubular element and spaced apart therefrom;
sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element.

30. The method of claim 29, wherein said inner tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium and zirconium.

31. The method of claim 30, wherein said radiation-emitting material comprises amaterial selected from the group consisting of: palladium-103, iridium-192, iodine-125, gold-1953, yttrium-90 and phosphorus-32.

32. The method of claim 31, wherein said radiation-emitting material is a quantity of radiation-emitting material having an activity of between 45.1 and 10,000 millicurie.

33. The method of claim 32, wherein said radiation-emitting material is an essentially uniform layer of radiation-emitting material.

34. The method of claim 29, wherein said outer tubular element comprises a material essentially transparent to the radiations emitted by said radiation-emitting material.

35. The method of claim 34, wherein said outer tubular element comprises a material selected from the group consisting of titanium, carbon, stainless-steel, tantalum, hafnium, zirconium, titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, and zirconium nitride.

36. The method of claim 35, wherein said first ends are sealingly joined and said second ends are sealingly joined by swaging said ends together and said ends are further joined by laser welding so as to form a sealed device.

37. The method of claim 29, wherein said depositing a layer of radioactive material is achieved by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

38. The method of claim 29, additionally comprising:
depositing a radiographically detectable band on a portion of said external surface of said inner tubular element by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

39. A method of making a double-walled tubular precursor device adapted to be transmuted into a brachytherapy device and having a lumen therethrough for interstitial inplantation of radiation-emitting material within a living body, said method comprising:
depositing a layer of isotope on an external surface of an inner tubular element, said inner tubular element having a first open end, a second open end, and a lumen continuous with said first open end and said second open end:
positioning said inner tubular element within an outer tubular element, said outer tubular element having a first open end, a second open end, and a lumen continuous with said first open end and said second open end, said inner tubular element being of substantially equal length to said outer tubular element, wherein said inner tubular element.
is disposed substantially centrally within said outer tubular element and spaced apart therefrom;
sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element.

40. The method of claim 39, wherein said inner tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium and zirconium.

41. The method of claim 40, wherein said isotope comprises a material selected from the group consisting of: palladium-102, iridium-191, gold-197, yttrium-539 and phosphorus-31.

42. The method of claim 41, wherein said isotope is disposed as an essentially uniform layer of isotope.

43. The method of claim 38, wherein said outer tubular element comprises a material essentially transparent to radiations emitted by said isotope after neutron irradiation of said double-walled tubular precursor device.

44. The method of claim 43, wherein said outer tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium, zirconium, titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, and zirconium nitride.

45. The method of claim 44, wherein sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element comprises swaging said ends together, and further sealingly joining said ends by laser welding, so as to form a sealed device.

46. The method of claim 38, wherein said depositing a layer of isotope is achieved by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

47. The method of claim 38, additionally comprising:
depositing a radiographically detectable band on a portion of said external surface of said inner tubular element by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

48. A method of making a double-walled tubular precursor device adapted to be transmuted into a brachytherapy device having a lumen therethrough for interstitial implantation of radiation-emitting material within a living body, said method comprising:
fabricating an inner tubular element, said inner tubular element being fabricated to have an external surface, a lumenal surface, a first open end, a second open end, and a lumen continuous with said first open end and said second open end;
fabricating an outer tubular element, said outer tubular element being fabricated to have a first open end, a second open end, and a lumen continuous with said first open end and said second open end, said tubular element also being fabricated to be of substantially equal length to said tubular support and of a diameter sufficient to permit said tubular support to be positioned within said lumen of said tubular element;

depositing a layer of isotope on said external surface of said inner tubular element;
positioning said inner tubular element within said outer tubular element so that said inner tubular element is disposed coaxially and substantially centrally within said outer tubular element and spaced apart therefrom;
sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element; and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element.

49. The method of claim 48, wherein said inner tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium and zirconium.

50. The method of claim 49, wherein said isotope comprises a material selected from the group consisting of: palladium-102, iridium-191, gold-197, yttrium-89 and phosphorus-31.

51. The method of claim 50, wherein said isotope is disposed as an essentially uniform layer of isotope.

52. The method of claim 47, wherein said outer tubular element comprises a material essentially transparent to radiations emitted by said isotope after neutron irradiation of said double-walled tubular precursor device.

53. The method of claim 52, wherein said outer tubular element comprises a material selected from the group consisting of: titanium, carbon, stainless-steel, tantalum, hafnium, zirconium, titanium carbide, titanium nitride, titanium carbonitride, hafnium nitride, and zirconium nitride.

54. The method of claim 53, wherein sealingly joining said first open end of said inner tubular element and said first open end of said outer tubular element, and sealingly joining said second open end of said inner tubular element and said second open end of said outer tubular element comprises swaging said ends together, and further sealingly joining said ends by laser welding, so as to form a sealed device.

55. The method of claim 48, wherein said depositing a layer of isotope is achieved by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

56. The method of claim 38, additionally comprising:
depositing a radiographically detectable band on a portion of said external surface of said inner tubular element by a process selected from the group consisting of chemoactivation, sputtering, vapor deposition plating, chemical-vapor deposition plating, electroplating and electroless plating.

57. A method of positioning during surgery, a double-walled tubular brachytherapy device having a lumen therethrough, said method comprising:
selecting a location where brachytherapy is desired to be delivered, said location being relative to the tumor to be treated, relative to the treatment volume to be irradiated, or relative to previously-applied brachytherapy devices;
inserting a double-walled tubular brachytherapy device in the vicinity of said location with a surgical needle; and positioning said double-walled tubular brachytherapy device at said location with said surgical needle;
whereby said double-walled tubular brachytherapy device may be located relative to a tumor, relative to a volume to be irradiated or relative to other brachytherapy devices.

58. The method of claim 57, wherein:
a plurality of double-walled tubular brachytherapy devices are inserted at said vicinity of said location with said surgical needle;
whereby said plurality of double-walled tubular brachytherapy devices may be located relative to a tumor, relative to a volume to be irradiated or relative to other brachytherapy devices.