U.S. patent application number 10/818207 was filed with the patent office on 2004-09-30 for radiation delivery devices and methods for their manufacture.
Invention is credited to Brauckman, Richard A., Dill, Glenn A., Moody, Michael R., White, Jack C..
Application Number | 20040192998 10/818207 |
Document ID | / |
Family ID | 22760754 |
Filed Date | 2004-09-30 |
United States Patent
Application |
20040192998 |
Kind Code |
A1 |
Brauckman, Richard A. ; et
al. |
September 30, 2004 |
Radiation delivery devices and methods for their manufacture
Abstract
Radiation delivery devices useful in brachytherapy which employ
radioactive palladium-103 as the radiation source material are
disclosed. Certain embodiments of the disclosed radiation delivery
devices have the advantages that they can be fabricated with the
desired specific activity, that the self-shielding effects of the
devices are minimized, that the radioactive source material is
bonded to a substrate in a manner which substantially prevents it
from becoming detached, and that a variety of customizable
radiation delivery devices can be made using the concepts of the
invention. Also disclosed are processes for bonding radiation
source material to various substrates using electroless plating,
chemical vapor deposition and polymer matrices. These processes
have the advantage that they can be applied to bond the radiation
source material to a wide variety of substrates including different
substrate materials and differently shaped substrates, thereby
providing the ability to tailor the radiation delivery devices to
the specific requirements of a particular brachytherapy
treatment.
Inventors: |
Brauckman, Richard A.;
(Cumming, GA) ; White, Jack C.; (Alpharetta,
GA) ; Dill, Glenn A.; (Fayetteville, GA) ;
Moody, Michael R.; (Marietta, GA) |
Correspondence
Address: |
KNOBLE & YOSHIDA, LLC
Eight Penn Center
Suite 1350
1628 John F. Kennedy Blvd.
Philadelphia
PA
19103
US
|
Family ID: |
22760754 |
Appl. No.: |
10/818207 |
Filed: |
April 5, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10818207 |
Apr 5, 2004 |
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09858816 |
May 16, 2001 |
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6749553 |
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60205090 |
May 18, 2000 |
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Current U.S.
Class: |
600/3 ; 604/19;
606/194 |
Current CPC
Class: |
A61N 2005/1025 20130101;
A61N 5/1027 20130101; A61N 2005/1023 20130101 |
Class at
Publication: |
600/003 ;
604/019; 606/194 |
International
Class: |
A61N 005/00; A61N
001/30; A61M 029/00 |
Claims
1. A radiation delivery device, which comprises: a flexible
substrate selected from the group consisting of flexible fiber and
flexible film formed from a radiation compatible material and which
is sufficiently flexible to deform under its own weight, and a
sufficient amount of radioactive palladium-103 bonded to the outer
surface of the substrate to provide an apparent activity of the
radiation delivery device, as measured adjacent to the surface of
the substrate, of from about 0.5 .mu.Ci to about 300 Ci/device, and
wherein the radioactive palladium-103 forms at least a portion of
the outer surface of the radiation delivery device such that the
radioactive palladium-103 can be positioned closely adjacent to, or
in direct contact with, a location to be treated with
radiation.
2. A radiation delivery device as claimed in claim 1, wherein the
radioactive palladium-103 is bonded to the outer surface of the
substrate by a deposition process selected from the group
consisting of electroless plating, electroplating, sputtering, ion
implantation, physical vapor deposition and chemical vapor
deposition.
3. A radiation delivery device as claimed in claim 1, wherein the
radioactive palladium-103 is dispersed in an outermost portion of
the substrate.
4. A radiation delivery device as claimed in claim 1, wherein the
radioactive palladium-103 is dispersed in a layer of material
located on the outermost surface of the substrate.
5. A radiation delivery device as claimed in claim 1, wherein the
radioactive palladium-103 is substantially homogeneously dispersed
over the entire outer surface of the substrate to thereby provide a
substantially uniform distribution of radiation from the radiation
delivery device.
6. A radiation delivery device as claimed in claim 1, wherein the
radioactive palladium-103 is non-uniformly dispersed over the outer
surface or within the outer surface of the substrate to thereby
provide a directional distribution of radiation from the radiation
delivery device.
7. A radiation delivery device as claimed in claim 1, wherein the
substrate comprises at least one material selected from the group
consisting of: polymeric materials, ceramic materials, hydrogels,
metals, graphite and ion exchange resins.
8. A radiation delivery device as claimed in claim 1, wherein the
substrate comprises a flexible material selected from the group
consisting of elastomers, gels and foams.
9. A radiation delivery device as claimed in claim 1, further
comprising a protective coating layer located on the outside of the
radioactive layer.
10. A radiation delivery device as claimed in claim 1, having an
apparent activity of from about 0.5 mCi to about 30 Ci per
device.
12. A radiation delivery device which comprises: a non-conductive
substrate; and a sufficient amount of radioactive palladium-103
bonded to the substrate to provide an apparent activity of the
radiation delivery device, as measured adjacent to the surface of
the substrate, of from about 0.5.mu. to about 300 Ci/device, and
wherein the radioactive palladium-103 comprises carrier-free
palladium-103.
13. A radiation delivery device as claimed in claim 12, wherein the
radioactive palladium-103 is bonded to the outer surface of the
substrate by a deposition process selected from the group
consisting of electroless plating, electroplating, sputtering, ion
implantation, physical vapor deposition and chemical vapor
deposition.
13. A deformable radiation delivery device which comprises: a
deformable substrate, and a sufficient amount of radioactive
palladium-103 bonded to the substrate to provide an apparent
activity of the radiation delivery device, as measured adjacent to
the surface of the substrate, of from about 0.5 .mu.Ci to about 300
Ci/device, and wherein the radioactive palladium-103 is bonded to
the deformable substrate in a manner whereby substantially no
radioactive palladium-103 detaches from the deformable substrate
under normal use conditions.
14. A deformable radiation delivery device as claimed in claim 13,
wherein the radioactive palladium-103 comprises carrier-free
palladium-103.
15. A deformable radiation delivery device as claimed in claim 13,
wherein the deformable substrate comprises an elastomer, gel or
foam.
16. A deformable radiation delivery device as claimed in claim 13,
further comprises a deformable coating of a biocompatible material
on the outer surface of the radiation delivery device.
17. A process for bonding a material selected from the group
consisting of palladium-102, palladium-104, radioactive
palladium-103, carrier-free palladium-103, naturally occurring
palladium, palladium enriched in palladium-102, palladium-104
enriched palladium and mixtures thereof, onto a substrate which
comprises the steps of: treating the surface of the substrate by
treating the substrate with a material selected from the group
consisting of a tin salt, a platinum salt and a palladium salt;
activating the treated substrate surface by contacting the treated
substrate surface with a compound selected from the group
consisting of palladium salts and platinum salts, and mixtures
thereof; and contacting the activated substrate surface with a
solution of a radiation source material selected from the group
consisting of palladium-102, palladium-104, radioactive
palladium-103, carrier-free palladium-103, naturally occurring
palladium, palladium enriched in palladium-102 or palladium-104 and
mixtures thereof, in a suitable solvent for a sufficient time to
bond a sufficient of amount of the radiation source material to the
substrate to provide a radiation delivery device with an apparent
activity of the radiation delivery device, as measured adjacent to
the surface of the substrate, of from about 0.5 .mu.Ci to about 300
Ci/device.
18. A process in accordance with claim 17, wherein the radiation
source material comprises carrier-free palladium-103.
19. A process in accordance with claim 18, wherein the substrate
comprises a non-conductive material.
20. A radiation delivery device produced by the process of claim
17.
21. A directional radiation delivery device which comprises: a
substrate; a radiation source material including at least some
radioactive palladium-103; and a shielding material which
substantially reduces the radiation emitted by the radiation source
material in at least one direction relative to the radiation
delivery device.
22. A radiation delivery device which comprises: a biocompatible
material in the form of an object selected from the group
consisting of a housing, a strand, a fibrous material, a mesh, a
flexible hollow tube and a matrix; and a plurality of radiation
emitting sources associated with said biocompatible material;
wherein said radiation emitting sources each comprise: a substrate;
and a radiation source selected from the group consisting of
pellets and microspheres and including at least some radioactive
palladium-103 bonded to the substrate.
23. A radiation delivery device as claimed in claim 22, wherein the
radiation source material is bonded to the outer surface of the
pellets or microspheres.
24. A radiation delivery device as claimed in claim 22, wherein the
radiation emitting sources comprise pellets or microspheres and the
radiation source material is dispersed in the substrate which forms
the pellets or microspheres.
25. A radiation delivery device as claimed in claim 24, wherein the
radiation source material is dispersed only in an outermost portion
of the microspheres.
26. A radiation delivery device as claimed in claim 22, wherein the
substrate is in the form of a fiber strand and the radioactive
material is coated on an outer portion of the fiber strand.
27. A radiation delivery device as claimed in claim 22, wherein the
substrate is in the form of a flexible hollow tube.
28. A radiation delivery device as claimed in claim 27, wherein the
radioactive material is located on the inner surface of the
flexible hollow tube.:
29. A radiation delivery device which comprises: a flexible hollow
tube; and a radiation emitting source located with the flexible
hollow tube; wherein said radiation emitting source comprises: a
flexible substrate selected from the group consisting of
elastomers, foams and gels; and a radiation source material
including at least some radioactive palladium-103 dispersed or
dissolved in the substrate.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to localized radiation therapy
and devices therefore. More particularly, thee present invention is
directed to radiation delivery devices using palladium-103, and to
their methods of manufacture.
BACKGROUND OF THE INVENTION
[0002] Radioactive materials have long been used in the medical
treatment of diseased tissues. Such radioactive materials may be
implanted into a patient at the site of the diseased tissue or may
be locally applied externally through the skin. In either case, it
is desirable to have the radioactive material in a form which will
permit it to be used to irradiate the diseased tissue while
minimizing damage to nearby healthy tissue. Therefore, it is
desirable to have a radiation delivery device which will uniformly
irradiate a diseased area with a controlled dosage of radiation
while minimizing the exposure of surrounding healthy tissue to the
radiation.
[0003] Interstitial implantation of radiation delivery devices for
localized tumor treatment has long been recognized. The advantages
of interstitial implants reside in their ability to concentrate the
radiation in a localized area thereby minimizing radiation exposure
to nearby healthy tissue. Commonly used implantable radioactive
materials include iridium-192, iodine-125, gold-198 and radon-222.
However, each radiation source type has limitations. For instance,
most of these isotopes emit high energy gamma rays and the energy
of their X-ray radiation is relatively low. Also, some of these
isotopes have relatively long half-lives which make them less
desirable for brachytherapy treatments.
[0004] Several types of radioactive implants are known from U.S.
Pat. No. 5,342,283 (Good). This patent discloses radioactive
implants such as microspheres, wires and ribbons coating with
radioactive metals by, for example, sputtering. The radioactive
implants disclosed in this patent are solid, seamless elements
which may be individually implanted or combined in intercavity
applicators with fabrics and in ribbons. A variety of different
radioisotopes are disclosed.
[0005] U.S. Pat. No. 4,323,055 (Kubiatowicz) discloses a
radioactive iodine seed wherein the carrier for the radioisotope is
a rod-like member which is detectable by x-rays and occupies a
substantial portion of the space within the seed. The radioactive
iodine is distributed on the carrier body using an ion exchange
process by first halogenating the carrier body and then conducting
an ion exchange reaction with the radioactive material.
Alternatively, the radioactive iodine can, be electroplated onto
the carrier body. The carrier body is placed within a biocompatible
container such as a titanium capsule for use.
[0006] U.S. Pat. No. 5,713,828 (Coniglione) discloses a
brachytherapy device formed from a hollow tube-shaped seed
substrate which allows association of the device with suture
material to prevent migration of the device in the body. The
radioactive material is distributed on the exterior surface of the
tubular device to provide a relatively uniform radiation field
around the brachytherapy seed source. A tubular, biocompatible
outer casing is placed around the inner, radioactive tube to seal
the radioactive material within the device. A variety of
radioactive materials are disclosed for use with the device.
[0007] In addition to the above mentioned radioactive materials, it
is also known to use palladium-103 in radiation therapy. Generally,
Pd-103 does not suffer from the high energy gamma radiation
problems associated with the previously mentioned isotopes.
Consequently, irradiation treatments employing Pd-103 radiation can
be more localized than with other radioactive isotopes thereby
reducing the potential for harm to nearby healthy tissue.
[0008] U.S. Pat. No. 4,702,228 describes therapeutic seeds
containing Pd-103 prepared by increasing the Pd-102 or content
found in palladium metal, i.e., by enriching palladium metal in
Pd-102 or content and then by exposing it to a neutron flux in a
nuclear reactor so as to convert a small fraction of the Pd-102
into Pd-103. Alternatively, Pd-104 enriched palladium can be
employed in which case the Pd-104 will be exposed to proton
bombardment to produce radioactive Pd-103.
[0009] Generally, palladium-103 is produced in a nuclear reactor by
bombarding a target containing Pd-102 with neutrons
(Pd-102(n,.gamma.) Pd-103). Since all of the Pd-102 nuclei are not
converted and, since in addition, other naturally occurring
isotopes of the element palladium are typically present in small
amounts in the target, Pd-103 cannot be produced in a carrier-free
state. By carrier-free state it is meant Pd-103 containing
substantially no other palladium isotopes. Since there are small
amounts other isotopes of Pd present in the target, neutron
activation products of these isotopes are produced as well. For
example, the reaction Pd-108(n,.gamma.)Pd-109 also occurs and
therefore Pd-103 obtained from a reactor by neutron bombardment
always contains a small amount of the radioisotope Pd-109. Since
Pd-109 is the same element as Pd-103, no chemical means are known
to effect their separation. The presence of other nuclides of Pd in
the target also leads to the production of significant amounts of
certain non-Pd radioisotopes, e.g. if radioactive Pd-111 is
produced, it will decay to another radioactive isotope, Ag-111,
further complicating the radiochemical purification of the Pd-103
matrix. In contrast, Pd-103 produced in a particle accelerator,
such as a cyclotron, may be obtained in a carrier-free state, i.e.
containing substantially no palladium isotopes other than
Pd-103.
[0010] Another drawback of radiation delivery devices produced in a
nuclear reactor from Pd-102 enriched palladium is that for
practical reasons soon to be apparent, one is obliged to use
reactor grade Pd-103 at the specific activity level generated in
the reactor. This places significant limitations on the level of
dosage that can be delivered by a device which employs reactor
grade Pd-103. In contrast, cyclotron-produced carrier-free Pd-103
can be employed in a way that provides for its economical
utilization while at the same time providing for a device having a
predetermined therapeutic or apparent activity.
[0011] The specific activity of Pd-103 that can be produced in a
nuclear reactor is determined by the level of enrichment of the
Pd-102 target used, the neutron flux in the reactor and the length
of exposure of the target to the neutron flux in the reactor.
Generally, the highest enrichment of Pd-102 available (Oak Ridge
National Laboratories (ORNL)) has an isotopic purity of 77.9%
Pd-102 with the remaining 22.1% of the target being made up of the
other isotopes of Pd. The highest neutron flux available in the
world is found in the ORNL HFIR facility where the level is
approximately 2.6E15 neutrons/cm.sup.2 sec. This reactor runs in 21
day cycles with approximately 10 days between cycles. Due to the
generation of extraneous isotopes such as Ag-111, the maximum
practical irradiation time is two cycles. These factors taken
together indicate the maximum specific activity that can be derived
from a nuclear reactor target is approximately 345 Ci/g. In
contrast, the specific activity of carrier-free Pd-103 can be as
high as 75,000 Ci/g.
[0012] As such, smaller amounts of carrier-free Pd-103 can be
employed in radiation delivery devices as compared to reactor grade
Pd-103 in order to achieve the same level of activity.
Additionally, a greater degree of control over the specific
activity of a particular device can be exercised when using
carrier-free Pd-103 since the only potential error factors which
enter into this process are the measurement of the specific
activity of the carrier-free Pd-103 and the provision of the right
amount for the desired level of specific activity in the device.
Therefore, for these reasons it is often preferably to employ
carrier-free Pd-103 in radiation delivery devices.
[0013] U.S. Pat. No. 3,351,049 to Lawrence et al. suggests the use
of carrier-free palladium-103 in therapeutic seeds. U.S. Pat. No.
5,405,309 to Carden, Jr. also discloses the use of carrier-free
Pd-103 in therapeutic seeds wherein carrier-free Pd-103 is mixed
with a small amount of palladium metal, electroplated onto a pellet
of electroconductive material, and encapsulated within a
biocompatible container. By virtue of the electroplating and
encapsulating procedures, a certain degree of self-shielding was
observed which affected the efficacy and potency of the therapeutic
seeds. However, such procedures were deemed necessary for proper
containment of the radiation source material. Further, the
therapeutic seeds disclosed in these patents are somewhat limited
in use by their rigid physical dimensions.
[0014] In view of the above, there has remained a need in the art
for versatile radiation delivery devices which exhibit reduced
self-shielding properties while effectively containing the
radiation source material.
SUMMARY OF THE INVENTION
[0015] It is an object of certain embodiments of the present
invention to provide radiation delivery devices comprising a
substrate and a radiation source material adhered to the outer
surface of the substrate or incorporated into the substrate,
wherein the radiation source material comprises carrier-free
Pd-103. A variety of different types of substrates may be employed
depending primarily upon the particular application for which the
device will be employed.
[0016] It is a further object of certain embodiments of the present
invention to provide methods for deposition of a radiation source
material onto a substrate.
[0017] It is yet another object of certain embodiments of the
present invention to provide a radiation delivery device, wherein
the substrate design, and/or the radiation source material
configuration is such that the device may provide a non-uniform,
i.e. directional, radiation distribution.
[0018] It is another object of certain embodiments of the present
invention to provide a radiation delivery device comprising a
substrate and a radiation source material deposited onto, or
incorporated into the substrate, wherein the substrate is shaped to
fill a body cavity and the radiation source material comprises
palladium-103.
[0019] It is a still further object of certain embodiments of the
present invention to provide a method for filling a body cavity
with such a radiation delivery device.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIGS. 1A-1B illustrate a thin film radiation delivery
device.
[0021] FIG. 2 shows a deformable radiation delivery device which
may be implanted within a body cavity.
[0022] FIGS. 3A-3B show flexible hollow tube radiation delivery
devices with a radioactive material on either an internal or
external surface of the device.
[0023] FIG. 4 shows a flexible hollow tube radiation delivery
device which houses radioactive components.
[0024] FIG. 5 shows a long flexible strand with a radioactive
material on a surface of the strand.
[0025] FIG. 6A shows a cross-sectional view of a fabric material
with a radioactive material on a surface of the fabric
material.
[0026] FIG. 6B shows a perspective view of a mesh made from the
fabric material of FIG. 6A.
[0027] FIGS. 7A-7B illustrate cross-sectional views of a
microsphere radiation delivery device according to one embodiment
of the present invention.
[0028] FIG. 8 illustrates a radiation delivery device comprising a
fiber with multiple microspheres containing radioactive material
attached thereto.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0029] Generally stated, a radiation delivery device embodying
features of the present invention comprises at least a radiation
compatible substrate and a radiation source. The substrate and
radiation source can either serve as a radiation delivery device,
or the combination can be incorporated into a structure, which will
serve as the radiation delivery device. The radiation source
material is associated with the substrate in some way and, for
example, can be incorporated into the substrate or applied onto the
outer surface of the substrate.
Substrate
[0030] The substrate can be formed from a non-toxic metallic,
non-metallic, polymeric, or ceramic material. The substrate can be
in the form of a fiber, strand, ribbon, mesh, patch, film, suture,
staple, clip, pin, microsphere, pellet, or the like. By pellet is
meant substrates including, but not limited to, rods, cylinders and
hollow tubes of different cross-sectional configurations. Further,
the substrate can be rigid, flexible, deformable, solid, hollow,
porous, or even sufficiently porous to allow for tissue growth
therein.
[0031] In one embodiment, the substrate can be a thin film, fiber,
ribbon, mesh, patch, suture, strand or the like formed from a
biocompatible polymeric material. The polymeric material is
preferably be selected from the group consisting of polyvinyl
chloride, polysulfones, cellulose esters, nylon, Dacron.TM.,
polyesters, polyolefins, polyurethanes, polyamides, polyimides and
modified versions of one or more of these materials, as well as any
other polymeric materials known by a skilled person to be suitable
for this purpose.
[0032] Radiation can cause degradation of certain polymeric
materials, as is known in the art. Particularly preferred polymeric
materials for forming the substrate are polymeric materials which
are resistant to such degradation due to exposure to radiation,
such as the radiation stabilized polypropylene materials disclosed
in U.S. Pat. Nos. 5,122,593 and 5,140,073, the disclosures of which
patents are hereby incorporated by reference to the extent that
they relate to radiation stabilized polymeric materials suitable
for use as substrates in the present invention.
[0033] Optionally, the polymeric materials forming the substrate
can include one or more additives to enhance the adherence of the
radiation source material to the substrate. Examples of such
additives include absorbent materials such as activated carbon
powder, activated charcoal, and ion exchange resins. Suitable ion
exchange resins include sulfonated polystyrene resins,
methylene-sulfonic phenolic resins, phosphoric polystyrene resins,
polystyrene resins containing quaternary ammonium groups,
pyridinium polystyrene resins, epoxy-polyamine resins containing
tertiary and quaternary ammonium groups, acrylic resins,
iminodiacetic polystyrene resins, and polystyrene resins containing
polyamine groups, as well as other ion exchange resins known to
persons skilled in the art.
[0034] In yet another embodiment, the substrate can be formed from
a biodegradable polymeric material such as polyethylene glycol or
polyethylene glycol--polyethylene oxide block copolymer. A
particularly preferred substrate is made from a flexible or
deformable material such as an elastomer, gel, foam or other
suitable, flexible polymer material. Exemplary, but not limiting,
polymeric materials include polyurethanes, silicones and
elastomers, gels or foams of polyurethanes and silicones. Again,
the key properties for use of these materials is that they must be
suitable for implantation in the body and exhibit good radiation
stability.
[0035] In an alternative embodiment, the substrate is a metallic
material, which may be in the form of a pellet, or microsphere. The
pellets or microspheres are preferably formed from a high atomic
number metal or alloy such as aluminum, iridium, platinum, gold,
tantalum, tungsten, lead and alloys of one or more of these or
similar metals. Additionally, any lower atomic weight metal or
alloy, which is satisfactorily visualized on radiographs may be
used including molybdenum, indium, lithium, silver, copper, and
stainless steel. Alternatively, when only magnetic resonance
imaging of the delivery device is clinically desirable, the
substrate can be a non-metallic pellet or microsphere formed from,
for instance, carbon, diamond, or graphite or non-magnetic metals
such as aluminum. The pellets or microspheres can be of any desired
shape, but are preferably spherical or cylindrical. Of these
substrates, graphite in the form of cylindrical pellets or
microspheres is particularly preferred.
Radiation Source Material
[0036] The radiation source material preferably comprises
carrier-free Pd-103, reactor grade Pd-103 or a mixture thereof. In
addition, the radiation source material may optionally include a
diluent as described below. The term "specific activity" as used
herein and in the appended claims means the total activity of the
Pd-103 per gram of the radiation source material.
[0037] Reactor grade Pd-103 may be prepared in any suitable
conventional manner such as by activation of palladium metal or by
fabrication in a nuclear reactor. One disadvantage of reactor grade
Pd-103 is that it may contain trace amounts other undesirable
radioactive palladium isotopes such as Pd-109 which emit
potentially harmful types of radiation. Reactor grade Pd-103 can be
fabricated to minimize such impurities. Nevertheless, in some
applications, particularly those where irradiation will occur close
to a vital internal organ, it may be desirable to avoid use of
reactor grade Pd-103 for this reason. Moreover, the specific
activity of reactor grade Pd-103 is relatively low as compared with
other forms of radioactive palladium-103.
[0038] The term "carrier-free palladium-103" as used herein claims
means palladium-103 which is fabricated in a particle accelerator
such that it is essentially free from palladium isotopes other than
palladium-103. Carrier-free Pd-103 is typically a highly pure
material which contains essentially no undesirable radioactive
isotopes of palladium. Moreover, carrier-free Pd-103 can be made
having extremely high activities relative to reactor grade Pd-103
thereby providing greater flexibility in adjusting the specific
activity of the radiation delivery device and permitting the use of
smaller quantities of the expensive palladium material to achieve a
desired level of radiation dose. In accordance with the present
invention, carrier-free Pd-103 can preferably be prepared in a
particle accelerator in accordance with the procedure given in
Example 1 below.
[0039] In a preferred embodiment, the radiation source material
further comprises a diluent. The diluent can be added to the
radiation source material after it is eluted off the final
purification anion exchange column. Alternatively, the diluent can
be added during or prior to a purification process, if the diluent
properties so allow. Suitable diluents for radioactive Pd-103 may
include palladium metal, rhodium metal, one or more of the various
substrate materials listed above, or any other suitable material
which is compatible with the radiation released by the Pd-103. More
preferred diluents are biocompatible materials. Preferred diluents
for carrier-free palladium are rhodium and palladium metals,
usually in the form of a soluble metal salt such as PdCl.sub.2.
Because palladium metal will have the same affinity for an anion
exchange column as the Pd-103, it can be added as a diluent prior
to a purification step employing an anion exchange column and can
be co-purified along with the radioactive Pd-103.
[0040] Other preferred diluents are certain polymeric materials
which can be employed as a diluent by, for example, homogeneously
mixing the radiation source material with the polymer prior to its
application to the substrate, or even by carrying out such mixing
and using the mixture of polymeric material and radiation source
material as the substrate itself.
[0041] Although the diluent may normally be considered an
undesirable additive in a low energy emitting radiation source due
to self-shielding effects, its addition in accordance with the
present invention has been found to be advantageous in several
respects which, in some applications, may make use of such a
diluent desirable. Foremost, the added diluent can serve to promote
strong adhesion of the radiation source material to the substrate,
thereby forming a physiologically inert layer which will not allow
the radioactive Pd-103 to be mobilized into the circulation of a
patient being treated.
[0042] Secondly, the addition of diluent provides the ability to
adjust the specific activity of the Pd-103 in the radiation source
material. This adjustment can be employed to provide an accurately
determined desired level of therapeutic or apparent activity, as
well as to compensate for the self-shielding effects of the
diluent. Thirdly, if purification of the carrier-free Pd-103 is
necessary, the presence of the diluent can, in some instances,
reduce the loss of Pd-103 occurring during the purification
process.
[0043] The amount of diluent added, therefore, will vary depending
principally upon the amount of carrier-free Pd-103 available.
Preferably, from about 0.1 mg to about 100 mg of diluent per
millicurie of radioactive source material area can be used. More
preferably, from about 1 mg to about 50 mg of diluent per
millicurie of radioactive source material is employed. Such amounts
of diluent can ensure uniformity of the radioactive Pd-103 in the
radiation delivery device and can promote adherence of the
radiation source material to the substrate.
[0044] If design considerations, e.g. the desired mass or
therapeutic activity of the delivery device, so allow, nuclear
reactor produced Pd-103 can be added as a diluent to carrier-free
Pd-103 and vice versa. Such addition may be employed, for example,
to adjust the therapeutic activity of the radiation delivery device
or to reduce the overall cost.
Radiation Source Material Incorporation Processes
[0045] As mentioned previously, the radiation source material can
be applied to the outer surface of the substrate or be incorporated
into the substrate. Particularly preferred methods for applying the
radiation source material onto the surface of the substrate include
electroless plating, electroplating, sputtering, ion implantation
including ion exchange processes, physical vapor deposition or
chemical vapor deposition ("CVD"). Other processes for associating
a radioactive source material with a substrate known to persons
skilled in the art may also be employed.
[0046] Electroless plating of Pd-103 onto a substrate has the
advantage that it the process is applicable to a wide variety of
substrates and is particularly useful for applying radioactive
source material to non-conductive substrates. The process of the
invention involves a first step of cleaning the substrate surface
to which the plating will be applied. Conventional cleaning
processes can be employed such as ultrasound, rinsing with solvents
and/or water, and other known surface cleaning processes. Once
cleaned, the surface of the substrate is pretreated with, for
example, SnCl.sub.2, a platinum salt or a palladium salt such as
PdCl.sub.2.
[0047] The pretreated substrate is then treated with, for example,
a PdCl.sub.2/HCl solution. The stannous ions cause the Pd.sup.2+
ions from PdCl.sub.2 to reduce to Pd.sup.0 and to adhere to the
substrate. These Pd.sup.0 sites form a catalytic surface on the
substrate to enhance the deposition of Pd-102 enriched palladium,
Pd-104 enriched palladium or radioactive Pd-103 onto the substrate
in a subsequent plating step. Other, similar metals, such as
platinum group metals, may also be used instead of palladium.
[0048] The Pd-102 or Pd-104 enriched palladium or radioactive
Pd-103 can then be deposited on the activated substrate by
submerging the substrate in a heated solution of Pd-102 or Pd-104
enriched palladium or radioactive Pd-103. Once the deposition
reaction subsides, the substrate plated with Pd-102 or Pd-104
enriched palladium or radioactive Pd-103 is then dried and cooled.
The electroless plating process has the additional advantages that
there is very little loss of expensive palladium during the process
and that a substantially uniform coating can be applied to a
substrate in a relatively short time period. Also, the electroless
plating process can be employed to apply a conductive coating onto
a non-conductive substrate as a pretreatment of the substrate to
prepare it for a subsequent electroplating step. Processes for
electroplating palladium-103 onto various electroconductive
substrates are known to persons skilled in the art from U.S. Pat.
No. 5,405,309, the disclosure of which is incorporated by reference
for the purpose of describing the details of a suitable
electroplating process.
[0049] Alternatively, the radiation source material can be
uniformly mixed with a diluent and then coated onto the outer
surface of the substrate. Suitable diluents for this purpose
include those described above as well as the substrate materials
described above which may be used in polymer masterbatching
processes, for example. Preferred diluents are adhesives and
polymeric materials such as, for example, urethanes, acrylics,
chloroprenes, polyvinylalcohols, polyvinylchorides, nylons, or the
like. It is preferred that the palladium be in solution when a
diluent is use, for example, in the form of palladium chloride or
palladium amine complex in solution, optionally in the diluent as
the solvent.
[0050] In embodiments where the radiation source material is
incorporated directly into the substrate, this can be accomplished,
for example, using ion implantation or by physically mixing the
radiation source material with the substrate material and then
forming the substrate from the mixture. For instance, the radiation
source material can be uniformly mixed with a polymer powder and be
incorporated into the polymer matrix upon polymerization to form
the substrate. Such a process is also applicable and particularly
preferred when employing elastomer, foam or gel substrates. In a
more preferred process, the radiation source material is mixed with
a polymeric material and subsequently coated, plated or otherwise
adhered to the outer surface of the substrate to form an outer,
radioactive layer. This delivery device has the advantages that the
radiation source material is firmly held in place in the polymer
matrix, while at the same time the bulk of the radiation source
material is located close to the surface of the substrate to
thereby minimize self-shielding effects.
[0051] In certain preferred embodiments of the present invention,
the radiation source material may be applied to the outer surface
of a polymer pellets, microspheres, powders or other similar
materials and then the solid polymers containing radioactive source
material are physically mixed with a substrate material as
described above. These embodiments are similar to polymer
masterbatching techniques known to skilled persons for the purpose
of incorporating various additives into polymeric materials.
[0052] The radiation source material can be supplied to
above-described incorporation processes as a solid or in solution,
as may be appropriate for the particular incorporation process. If
supplied as a solid, the radiation source material can be
carrier-free Pd-103 powder, or a mixture of carrier-free Pd-103 and
a suitable solid diluent. Alternatively, the radiation source
material may be supplied as solid reactor grade radioactive Pd-103
or as a solid form of Pd-102 or Pd-104 enriched palladium which may
later be activated to radioactive Pd-103, in situ, after
application of the Pd-102 or Pd-104 to the substrate of the
radiation delivery device.
[0053] If supplied as a solution, the radiation source material can
be, for example, a palladium amine complex obtained directly from a
purification process. Alternatively, Pd-102 or Pd-104 enriched
palladium or Pd-103 can be dissolved in an appropriate solvent to
obtain a desired solution for a particular incorporation process.
Suitable solvents for these materials are known in the art.
Delivery Devices
[0054] As discussed above, the substrate can itself serve as the
radiation delivery device, or the substrate and radiation source
can be incorporated into a structure, which serves as the radiation
delivery device. In any event, the term, "therapeutic activity" or
"apparent activity" as used herein and in the appended claims means
the total activity of the Pd-103 as determined from measuring the
radiation intensity just outside the radiation delivery thereby
taking into account the self-shielding properties of Pd-103 and any
other materials contained in the device which may shield the
radioactivity. A particularly suitable method for measuring the
activity of a device is the Air Kerma method certified by the U.S.
National Institute of Standards.
[0055] In a preferred embodiment of the present invention, the
device the radiation source material coated onto the outermost
surface of a substrate or dispersed into the outermost layer of the
substrate. The radiation delivery devices of the present invention
can be implanted at one or more selected sites within a living body
to emit localized radiation. The selected implantation site can be
located near a target site to be treated. Alternatively, the
delivery device can be implanted directly into a body cavity to be
treated wherein the delivery device is shaped such that, when
implanted, it substantially fills the body cavity to be treated. As
is apparent to one of ordinary skill, such a body cavity can be
naturally occurring within the body, artificially created as by
surgery, or a combination thereof.
[0056] As shown in FIGS. 1A-1B, films provided with a radioactive
material can serve as radiation delivery devices either directly or
in the form of a patch. Such a radiation delivery device can, for
example, be sutured in place or an adhesive can be applied to one
surface of the device to adhere it in place. Other suitable means
known to skilled persons for attaching films, patches or bandages
to the body can also be employed to secure the film-based delivery
device in place for treatment.
[0057] As shown in FIGS. 1A-1B, a film-based radiation delivery
device 10 can be provided by securing a radiation source material
12 to a film substrate 11 by any of the processes described above
for incorporation of the radiation source material into or onto
substrate 11. In addition, radiation source material 12 can be
adhered to film substrate 11 by mechanical attachment such as an
adhesive layer 14 or any other suitable mechanical attachment known
to suitable by skilled persons. The radioactive source material 12
may be coated on the surface of the film substrate 11 or may be
incorporated directly into the film substrate 11. If the
radioactive source material is directly incorporated into the film
substrate 11, it is preferably located close to the outer surface
of the film substrate 11.
[0058] The film-based radiation delivery device 10 is particularly
suitable for treatment of areas having a flat surface or areas
where the film substrate 11 can be attached to the body by, for
example, sutures, adhesive material or other suitable attachment
means or the film can be shaped to the contour of the body tissue
in the treatment zone. In a preferred embodiment, the film
substrate 11 is absorbable so that the film-based radiation
delivery device 10 can be implanted and left in place
permanently.
[0059] Referring now to FIG. 2, another aspect of the present
invention provides a flexible or deformable delivery device 10.
Such a flexible delivery device 10 can employ a substrate such as
an elastomer, gel, foam or the like as the carrier for the
radioactive source material. Such a flexible delivery device 10 is
particularly suitable for use in customizable radioactive implants
or delivery systems. For example, any biocompatible, radiation
stable device having an internal cavity can be employed to deliver
the flexible delivery device 10 of the present invention since the
flexible material can be conformed to the shape and size of the
cavity for each use. As a result, a hospital can have a supply of
radioactive material on hand which can be employed in a variety of
different types of delivery systems for different applications and
indications.
[0060] The flexible or deformable delivery device 10 can also be
used, for example, in a method for substantially filling a body
cavity 30 with a radiation delivery device 10. Such a method
involves the step of implanting a radiation delivery device 10 into
a body cavity 30, wherein the radiation delivery device 10 is
shaped such that, when implanted, it substantially fills the body
cavity to locally emit radiation therein. The radiation delivery
device 10 employed in this embodiment preferably comprises a
deformable substrate 11c with a radiation source material 12
located on its outer surface or impregnated or absorbed in an outer
layer of the deformable substrate 11c. The deformable substrate 11c
enables the delivery device to conform to the contours of the body
cavity 30. The flexible or deformable delivery device 10 may also
be shaped to conform to a particular body structure depending upon
the treatment application.
[0061] The flexible or deformable delivery device 10 may also be
used in combination with one or more of the other embodiments of
the invention described below. For example, a flexible hollow tube
21 can be filled with an elastomer, foam or gel containing
radioactive material to provide a radiation delivery device. Other
combinations of this embodiment with other embodiments of the
invention are also possible, particularly if it is desirable to
customize the radiation dose of a particular device on site for
use.
[0062] Referring to FIGS. 3A-3B, there is shown flexible hollow
cylindrical tubular radiation delivery devices 20. The flexible
tube 21 is formed from a deformable substrate such as the polymers
mentioned above. In FIG. 3A is shown a flexible hollow tube 21
having a coating of radioactive material 22 on the outer surface
thereof. In FIG. 3B is shown a flexible hollow tube 21 having a
coating of radioactive material 22 on the inner surface of the
flexible tube 21. The radioactive material may also form part of
flexible tube 21 in which case it is preferably dispersed evenly
throughout the material of flexible tube 21 or evenly over an area
located adjacent to the outer surface of flexible tube 21.
[0063] This flexible tube 21 can be used in a variety of
applications either alone or in combination with a housing or
affixation device to house or affix the flexible tube 21 for the
treatment process. In one embodiment, the flexible tube can be
sutured in place by running sutures through the center of flexible
tube 21. In another embodiment, flexible tube 21 can be attached to
a catheter for delivery to a desired treatment zone. Preferably,
flexible tube 21 is fabricated in lengths such that it can be cut
to the desired length for a particularly treatment.
[0064] FIG. 4 shows a flexible radiation delivery device 10
including a capsule 13b filled with microspheres 10a. The capsule
13b can be fabricated to any desired length or capsule 13b can be
fabricated and then a section can be cut to the desired size for
each specific application of the radiation delivery device. The
number of microspheres 10a associated with the containment
structure can vary depending on the desired therapeutic activity as
well as the activity of each microsphere 10a. Alternatively,
pellets may be employed instead of microspheres 10a. In this
manner, customized delivery devices having a variety of shapes,
sizes and therapeutic activities can be manufactured at low cost
with little waste.
[0065] FIG. 5 depicts a radiation delivery device 30 fabricated
from a long flexible strand 31, which may be made from any of the
various polymers mentioned above. Radioactive material 32 is
preferably coated on the surface of flexible strand 31 though it
may be impregnated in or incorporated in flexible strand 31 using
any of the suitable methods described above. Flexible strand 31 can
be employed in a variety of applications but is particularly
suitable for use as a suture or for the fabrication of a mesh or
fabric material, which may be employed as a radioactive source.
Flexible strand 31 has the advantage that it can be cut to the
desired size and that it can be employed in a variety of different
configurations such as a wrap around a delivery device, woven
through a stent or porous implant or sewn or tied to a part of the
body to be treated. Flexible strand 31 may have a variety of
different flexibilities. Preferably, flexible strand 31 is
sufficiently flexible that it will bend under its own weight such
that flexible strand 31 will behave like a piece of string or a
suture or the like. Various other applications for the flexible
strand 31 will be apparent to those of skill in the art.
[0066] FIGS. 6A-6B show a fabric material 40 with a radioactive
material 41 on the surface of the fabric 40. This fabric material
40 can be employed in the same manner as the film 10 shown in FIG.
1 or it can be used in a variety of other applications. The fabric
material 40 has the advantage that it is porous and thus will allow
passage of fluids therethrough. As a result, this type of radiation
delivery device breathes which may be an advantage in helping to
prevent infection. Moreover, the fabric material 40 can be attached
to the body or other devices in any number of ways some of which
may take advantage of the weave of the fabric in order to provide a
secure attachment. The fabric material 40 may be tightly woven or
loosely woven to form a mesh material, depending on the particular
application for which it is to be used. The fabric material may
optionally be coated with an outer coating 42 on the outside of the
radioactive material 41 to isolate the radioactive material 41 from
contact with the body, if desirable. The fabric material is
preferably sufficiently flexible that it will deform under its own
weight so that it can easily conform to the desired shape.
[0067] With reference to FIGS. 7A-7B, radiation delivery devices 10
formed from individual microspheres are illustrated in
cross-section. In FIG. 7A, a hollow microsphere substrate 11a
coated with a layer of radiation source material 12 is depicted.
FIG. 7B illustrates a solid microsphere substrate 11b coated with
radiation source material 12. Pellets may also be made which are
similar to the microspheres shown in FIGS. 7A-7B.
[0068] FIG. 8 shows a radiation delivery device 10 comprising a
fiber structure 13a with microspheres 10a attached thereto. The
microspheres 10a may be formed from a hollow microsphere substrate
11a coated with a radiation source material 12 as shown in FIG. 7A
or with a solid microsphere substrate 11b as shown in FIG. 7B. The
fiber structure 13a can be employed in a manner similar to the film
of FIG. 1 or the mesh shown in FIG. 6 above.
[0069] Preferably the radiation source material is located on the
outer surface of the delivery device. Locating the radiation source
material on the outer surface of the device minimizes the extent of
self-shielding and thereby reduces the amount of radiation source
material required to achieve a desired therapeutic activity. It is
believed that such a preferred configuration is made possible due
to the unique proprieties of Pd-103 and the novel methods for
incorporating the radiation source material into the delivery
devices described herein. More particularly, the methods for
incorporating the radiation source material into the delivery
devices described herein are believed to result in sufficient
bonding strength of the Pd-103 to the substrate to adequately
prevent the migration of the radiation source material away from
the delivery device during the time period that the Pd-103 emits
potentially harmful levels of radiation. Moreover, it is considered
that Pd-103 is sufficiently biocompatible that it can be employed
in direct contact with at least some body tissue without producing
significant detrimental effects.
[0070] However, if desired for an enhanced degree of safety or for
specific applications, particularly in sensitive areas of the body,
the delivery device can optionally be coated or sealed by an inert
biocompatible material to inhibit migration or diffusion of the
radiation source material into the patient. Such biocompatible
materials can include films or coatings of polymers such as
polyolefins, acrylates, polyurethanes, polyamides, polyimides,
polyesters, polyvinyl chloride, cellulose esters, polysulfones,
cyanoacrylates, modified versions of any of these materials and
mixtures thereof. Alternatively, the biocompatible materials can be
biocompatible metals such as titanium, stainless steel, tantalum,
platinum, palladium or gold. Such biocompatible materials can be
applied to the substrate containing radioactive material using any
method known in the art. Of course, the self-shielding properties
of such materials should be taken into consideration and minimized
or at least equalized over the entire substrate, where
possible.
[0071] The amount of radiation source material incorporated into
the delivery device depends primarily upon the therapeutic
radiation dosage required and the activity of the particular
radioactive Pd-103, which is employed. For instance, a specific
activity of at least 2.5 Ci/g is usually desirable for therapeutic
brachytherapy applications. The total radiation level emitted by
the delivery device, i.e., the therapeutic activity, is more
accurately expressed as an apparent value in mCi measured just
outside the radiation delivery device which takes into account any
self-shielding within the device which may occur, however minimal.
By adjusting the specific activity of the radiation source material
and the amount of the radiation source material incorporated into
the delivery device, the therapeutic activity level of the delivery
device can be adjusted to preferred apparent activity levels of
from about 0.5 .mu.Ci to about 300 Ci per device and more
preferably from about 0.5 mCi to about 30 Ci per device is
employed.
Directional Devices
[0072] In another embodiment of the present invention, the
radiation delivery devices can be fabricated to provide a
directional radiation distribution. More specifically, if a
particular treatment demands that radiation need only be directed
towards a particular location, it may be advantageous to fabricate
a directional radiation delivery device which can be employed to
selectively irradiate neighboring tissue without irradiating other
neighboring tissue.
[0073] Directional devices can be made in at least two ways,
selectively shielding a part of the device or controlling the
location of the radiation source material relative to the
substrate. In the first alternative, the device may be selectively
shielded at predetermined locations to provide for non-uniform,
i.e., directional, radiation distribution. Such selective shielding
can be accomplished by the incorporation of a shielding component
into the delivery device at one or more predetermined locations or
by fabricating all or a portion of the substrate from a shielding
material. Shielding components can include radiation absorbing
materials such as tin, silver, platinum, gold, tungsten, stainless
steel, lead, brass, copper, or alloys thereof. More preferably,
biocompatible shielding components are employed. The various
embodiments of the flexible or deformable radiation delivery
devices described herein can be directly adhered or attached to a
shielding substrate in any suitable manner in order to provide a
directional device.
[0074] Alternatively, directional radiation distributions can be
accomplished by controlling the location of the radiation source
material in or on the substrate and/or the location of the
substrate in the overall delivery device. For example, the
radiation source material may be applied to only one side of a
substrate. This can be effectuated by providing some type of
shielding material as the substrate, incorporating a shielding
material into the substrate or even by provide a relatively large
substrate such that radiation from the radiation source material
has to travel a larger distance in one direction than another
direction to impact body tissue. Since the effect of the radiation
from palladium-103 is inversely proportional to the distance
traveled by the radiation, a significant decrease in the exposure
level of adjacent body tissue can be achieved merely by requiring
the radiation to traverse such a distance or vary the attenuation
on the surface of the device by providing a variation in the
relative amounts of shielding. Alternatively, the depth at which
the radioactive material is located within the substrate can be
varied in order to vary the attenuation of the radiation and
thereby give the desired directional effect to the device..
[0075] Optionally, the radiation delivery devices of the present
invention can further include a marker to enhance imaging of the
delivery devices once inside the body. The marker is generally
comprised of a high atomic number element which, as a result of its
high atomic number, is X-ray opaque. Suitable examples of such
elements are known to persons skilled in the art and include lead,
barium, gold, tungsten, cobalt, platinum and rhodium. The marker
can also be fabricated in a way that the orientation of the device,
if significant, can be determined from the orientation of the
marker in an x-ray, i.e. by providing a non-symmetrical marker
having a known orientation relative to the radiation delivery
device. This type of marker is particularly useful for the
directional radiation delivery devices of the present
invention.
[0076] The following examples are included to further illustrate
the invention.
EXAMPLE 1
[0077] A target for use in the charged particle accelerator is
prepared by depositing rhodium metal onto a suitable substrate such
as a copper or a silver substrate. The rhodium target thus prepared
is then placed in a charged particle accelerator such as a
cyclotron and bombarded with protons or deuterons. The energy of
the impacting particles is chosen so substantially the only
radioactive material created on the rhodium target is Pd-103, that
is, the Pd-103 is carrier-free.
[0078] The rhodium metal containing the carrier-free Pd-103 is then
placed in a hot cell wherein the rhodium metal is removed from the
substrate by, for example, etching away with HNO.sub.3. This
removal is preferably accomplished by mechanically disrupting the
continuity of the rhodium layer on the substrate as by perforating
the surface with a sharply pointed impact tool. The exposed
substrate surface is covered to protect it and the perforated
target is immersed in a HNO.sub.3 bath. A solution containing
rhodium flakes results, which is filtered to recover the solid
rhodium flakes containing Pd-103. The recovered rhodium flakes are
rinsed on the filter and the flakes together with the filter are
placed in a crucible and heated to decompose the filter leaving the
rhodium metal flakes containing the Pd-103.
[0079] The rhodium metal flakes thus obtained are then partially
dissolved in molten NaHSO.sub.4 and the resulting
NaHSO.sub.4/rhodium flake mixture is dissolved in dilute HCl which
provides soluble rhodium salts dissolved in dilute HCl. This
procedure is normally repeated several times so as to dissolve any
remaining rhodium metal containing carrier-free Pd-103.
EXAMPLE 2
[0080] This procedure demonstrates a procedure for the electroless
plating of carrier-free Pd-103 onto a graphite substrate.
[0081] Initially, the graphite substrate was cleaned by ultra-sound
or sonication using deionized water.
[0082] Once cleaned, the graphite substrate was pretreated with
SnCl.sub.2. The stannous ions produced in this step attract
palladium ions later in the activation process.
[0083] The pretreated graphite substrate was then activated with a
PdCl.sub.2/HCl solution.
[0084] The stannous ions from the previous step cause the Pd.sup.2+
ions from PdCl.sub.2 to reduce to Pd.sup.0 and to adhere to the
substrate. These Pd.sup.0 sites form a catalytic surface on the
pellets which enhances the deposition of radioactive Pd-103 onto
the substrate in the subsequent plating step.
[0085] Carrier-free Pd-103 was then deposited on the activated
graphite substrate by submerging the substrate in a heated solution
of carrier-free Pd-103. Once the deposition reaction subsided, the
graphite substrate plated with carrier-free Pd-103 was then dried
and cooled to provide a radiation delivery device in accordance
with the present invention.
EXAMPLE 3
[0086] The procedure of Example 2 was followed except that a
polyurethane material was employed as the substrate to provide a
flexible substrate. A flexible radiation delivery device was
obtained.
EXAMPLE 4
[0087] A flexible film including a radioactive material was
fabricated in accordance with the process of Example 3. The film
was then adhered to a gold shield thin enough to be flexible. The
gold shield provided significant attenuation of the radiation and
as a result a flexible, directional radiation device was
obtained.
[0088] The foregoing examples have been provided for the purpose of
illustration and description only and are not to be considered as
limiting the scope of the invention in any way. The scope of the
invention is to be determined from the claims appended hereto.
* * * * *