Note: Descriptions are shown in the official language in which they were submitted.
CA 022',6189 1998-12-1',
METHOD AND SYSTEM FOR MAKING RADIOACTIVE
SOURCES FOR INTERSTITIAL BRACHYTHERAPY
AND SOURCES MADE THEREBY
BACKGROUND OF THE INVENTION
The invention relates to brachytherapy, which is a specialty within the medical field
of radiation oncology. More particularly, it relates to a method and system for
m~nllf~c~lring the small radioactive sources used in interstitial brachytherapy, and to the
radioactive sources per se. Such sources are surgically implanted, either temporarily or
pelmallell~ly, in close proximity to (lice~ed tissue about to undergo treatment by the
radiation emissions from the sources. ~Note: the prefix brachy in the word brachytherapy is
from the Greek word brachys, ~ g close or short).
Interstitial brachytherapy sources may be of solid, unitary construction and entirely
composed of bio-colllpalil)le materials, or they may be composed of radioactive and other
materials sealed inside bio-compatible capsules or coatings. Outwardly, they are usually
2 o metal cylinders with dimensions in the ranges: length 2 to 5 millimetPrs and diameter 0.2 to
I millimeters. The sources rely for their effectiveness upon the photon radiations, i.e. Xrays
and gamma-rays, emitted by certain radioisotopes. The amount of radioactivity colll~ined
by each sources can vary from 0.1 to 1 00 millicuries (mCi) but is usually in the range 0. 5 to
10 mCi. For coll"Jlehensi~7e i~oll~la~ion on interstitial brachytherapy source types and their
applications, the reader is referred to the textbook: Interstitial Brachytherapy - Physical,
Biological and Clinical Considerations", Interstitial Collaborative Working Group, Raven
Press, New York (1990), ISBN 0-88167-581-4.
Brachytherapy has been practiced since early this century, starting shortly after the
discovery of radium by the Curies in 1898. Many di~erenl source types have been
developed over the intervening years. These have been based upon radioisotopes widely
ranging in their half-lives and emission energies, and m~mlf~ctllring processes have
correspondingly varied. Over the last few dec~de~, most sources have been made by
irradiating preformed, solid, unitary "seeds" with neutrons in nuclear reactors. (Note:
CA 022~6l89 l998- l2- l~
finished interstitial brachytherapy sources ready for implant are often called seeds, but in
this document the word seed is reserved for a plerolllled solid substrate which is not yet
made radioactive to any degree, or is in the process of being made fully radioactive for
purposes of making a finished brachytherapy source). This simple and economical
approach yields suitably radioactive sources in batch sizes on the order of 10,000 units
ready for use without further processing. The most prevalent of this type have been
iridium-192 sources, which are made from iridium-platinum alloy seeds. These aregenerally employed as temporary implants. Although somewhat in decline because the
energies of their emissions are now considered to be higher than desirable, iridium-192
sources are still used in the largest numbers in interstitial brachytherapy.
Within the last ten years, other trends have become appal~ . There are strong
plerelellces developing in favor of permanent implant sources and radioisotopes ~milting
only low-energy photon radiations and having half-lives in the 10 to 100 day range. The
main reasons for the change in outlook are: a) permanent implants involve only a single
surgical procedure and result in lower hospital costs because of short patient stays with no
delays or returns for implant removals; b) low photon energies mean less penetrating
power, leading to less radiation exposure of healthy tissue surrounding the (li~e~ced tissue
region, as well as greatly reduced cllm~ tive radiation doses to hospital personnel; and c)
half-lives in the 10 to 100 day range allow the right amount of radiation to be delivered at a
2 o rate close to optimum with respect to therapeutic effect.
The two main low-energy sources in col.lme -,ial supply, and now do~ g the
overall brachytherapy source market in monetary terms, are encapsulated types with
radioactive contents sealed inside welded titanium capsules. They are based on the
radioisotopes p~ m-103 (half-life 17 days) and iodine-125 (half-life 60 days). Although
these sources types do possess the virtues d~line~ted for low-energy sources in the
preceding paragraph, both are far from ideal in other illlpOI l~l aspects: a) the
encapsulation material strongly ~ttem'~tes the low-energy radiation output; b) because they
are quasi line sources they have poor isotropy (equality in all directions) of their radiation
distributions, which negatively effects treatment planning and outcome; and c) both are
much more expensive and physically larger than the sources being displaced. These
CA 022~6l89 l998- l2- l~
deficiencies stem largely from their designs and the con~ of their m~mlf~hlring
methods.
There are two methods of making p~ m-103 prep~lions to serve as
feed-stocks in commercial brachytherapy source m~mlf~ctllring processes, where source
batch sizes are typically 100 to 10,000 units. The first method involves the irradiation of a
p~ linm target with neutrons in a nuclear reactor, the target having been artificially
enriched in the p~ inm-102 isotope prior to the irradiation. The stable p~ illm-102
nuclei capture neutrons to become radioactive p~ lm-103 nuclei. The irradiation is
followed by radio-chemical processing of the target. This results in a solution pl~pal~lion
containing p~ lm- 103 with a specific activity that typically would be on the order of 100
Curies of p~ (lillm 103 per gram of p~ rlillm, which is quite adequate for making
brachytherapy sources.
The second method of producing p~ll~(lillm-103 has largely supplanted the first
method for commercial purposes. It involves the irradiation in high vacuum of a stationary
rhodium metal target with a beam of energetic protons. The protons are produced in a
charged-particle accelerator that is usually of the type called a cyclotron. The protons
typically have energies incident on the target in the 15 to 20 MeV (million electronvolt)
range, which is applop.iate because the peak of the excitation function of the desired
nuclear reaction is at about 12 MeV. The beam current is usually on the order of 1
milli~mpere and irradiation periods are typically 10 to 100 hours. The rhodium target,
which may be internal or external to the cyclotron, is in the form of a single mass of
high-purity rhodium metal electro-plated on a water-cooled metal backing. In this case,
there is no artificial enrichment of the target atoms because natural rhodium is 100%
composed of the desired rhodiumlO3 stable isotope atoms. Under irradiation, any
rhodium-103 atom in the target and within the proton beam may capture a proton and
ec~.nti~lly ~imnlt~neously eject one of its neutrons, thus forming a p~ linm-103 nucleus.
This nuclear reaction is written as Rh-103(p,n)Pd-103. It occurs repeatedly during the
irradiation and builds up the desired radioactive p~ (lillm-103 product within the rhodium
target mass. Very little in the way of troublesome radioactive impurities are produced.
A~er the irradiation, the target is dissolved and the p~ lillm-103 is radio-chemically
CA 022~6189 1998-12-1~
separated from the rhodium, which is usually recycled to make another target. The
resulting p~ lm solution p-~pa,~ion could be e~nti~lly free of stable p~ m atomsand could have a specific activity approaching the theoretical maximum value of about
75,000 Curies of p~ m-103 per gram of p~ m Usually, however, some natural
pAl~ lm iS deliberately added in the process, and the specific activity ofthe plep~lion is
typically in the range 10 to 100 Curies per gram, similar to reactor-derived plepa~lions.
The sequestering and encapsulation of radioactive materials in small containers for
brachytherapy purposes are described in U.S. Patent Nos. 1,753,287; 3,351,049;
4,323,055; 4,702,228; 4,891,165; 4,994,013; 5,342,283; and 5,405,309. With the
exception of U.S. Patent No. 1,753,287, these descriptions taken together sun~l.a ~e the
technologies developed to date or formally envisioned for the commercial, large scale
production of lowenergy brachytherapy sources based on p~ (lillm 103 and iodinel25.
They involve sequential, labor and capital intensive processes which usually include the
following steps: a) separate m~nllf~chlring of radioisotope p.epa.~lions ~.nt~iling
irradiations and radio-chemical operations; b) loading portions of the radioisotope
p~pa~Lions onto substrates by chemical, physical or mechanical means, followed by
further operations if necessary, such as drying; and c) sealing the loaded substrates in bio-
compatible welded met~ capsules, c~ alternatively, coating the substrates with one or more
sealing materials, the outer of which must be a bio-compatible material.
SUMMARY OF THE INVENTION
In principle, and in contrast, the present invention makes un-encapsulated
p~ lm-103 sources in large batches by a simple and economical method which avoids
2 5 radio-chemical operations, encapsulations and associated costs and product problems. One
embodiment is effected by irradiating a batch of pler~,-l--ed rhodium metal seeds with
protons from a chargedparticle accelerator to directly yield sources ready for implantation.
The proton beam energy and current are similar to those used in conventional
p~ lm 103 production and the nuclear reaction is the same, as outlined above. The
3 0 method is feasible because: a) rhodium and p~ lm metals are members of the platinum
CA 022~6189 1998-12-1~
group of inert, bio-colllpalible metals which are not attacked by and do not react with body
tissues and fluids in any way, are not physiologically toxic or otherwise harmful, and
therefore do not need encapsulation before implantation; and b) proton bombardment of
rhodium to make p~llatlillm-lO3 in good yield results in low and tolerable levels of
undesirable radioactive by-products which might otherwise be troublesome from a
radiological protection viewpoint.
There are, however, three formidable problems in making p~ dillm 103 sources
employing this direct approach. The first problem is connected with the characteristics of
proton beams and the ways in which protons interact with matter. A proton beam is
produced and sustained under vacuum in a charged-particle accelerator and is highly
directional. Typically, the proton current is unevenly distributed over a beam
cross-sectional area of l to 2 square c~.ntimeters. Because protons carry an electric charge,
they do not easily pe~ e matter and quickly lose energy as they do so. Since yields of
nuclear reaction products induced by proton beams in target materials depend strongly on
proton energy, these yields also depend upon depth of penetration of the protons into the
target materials. Therefore, a stationary and multi-layered mass of hundreds or thousands
of rhodium seeds could not be irradiated with a proton beam with s~lcce~fill outcome in
the sense of yielding finished sources having apploxilll~lely equal ~mou~tc of p~ (lium-lO3
radioactivity distributed in an equivalent and suitably symmetric way within each source.
2 o The protons would barely penetrate the first layer of seeds, and even in these the resulting
p~ lm 103 would not be evenly and suitably distributed.
The second problem is connected with target heating. Each proton in the proton
beam in the situation contemplated would carry 10 to 20 MeV of kinetic energy. The beam
current would be expected to be in the range O.l to I milli~ pele to yield an adequ~te
p~ tlillm-103 production rate for commercial purposes. The beam power would be
expected, therefore, to be typically in the range l-20 kilowatts and this power would be
deposited in the collective rhodium seed target as heat. A stationary, uncooled mass of
rhodium seeds in a vacuum could sustain such rates of heat deposition for only seconds
without some melting and evaporation occurring.
The third problem is connected with source self-shielding. P~ tlillm-103 has very
CA 022~6l89 l998- l2- l~
low-energy photon emissions which are in the 20 to 25 keV (thousand electron-volts)
range. These photons are easily stopped by very thin layers of solid materials, incl~ltling
rhodium itself. The energy of the protons incident upon a rhodium seed is preferred to be in
the range 10 to 20 MeV in order to obtain a good production rate of p~ll~(lillm-103
Protons with energies in this range penetrate rhodium metal to a depth of 0.2 to 0.7
millimet~rs. With a source made by means of normal (90 degree angle) or near normal
incidence of the protons on a rhodium, seed, too great a fraction of the p~ m-103
produced would lie at depths below the surface of the seed such that nearly all of the
low-energy photon radiation emitted by that p~ (lillm 103 would be absorbed by the
source itself This radiation would be ineffective therapeutically.
Resolution of the above problems requires judicious selections of proton energies
and currents, and shapes and sizes of rhodium seeds, in order to balance p~ (lillm 103
production ratel source self-shielding, and brachytherapy considerations. It also requires
charged-particle accelerator target technology in order to present a target batch of rhodium
seeds to a proton beam with the seeds in a desired orientation and in such a way that all of
the seeds are equally, symmetrically and otherwise suitably irradiated, and that the heat
generated by the beam in the collective rhodium seed target is removed.
The first object of the invention is to economically provide safe, effective,
un-encapsulated p~ lillm 103 brachytherapy sources by directly irradiating preformed
rhodium metal or rhodium alloy seeds with energetic protons from a cyclotron or other
charged-particle accelerator.
Another object of the invention is to provide p~ lillm-103 sources in various
dimensions, shapes, radiation output distributions and radioactivity levels that address
various brachytherapy applications.
Another object of the invention is to provide a p~ lmlO3 source type having
superior isotropy of radiation distribution relative to the low-energy source types currently
commercially available.
Another object of the invention is to provide a p~ illmlO3 source type that is
smaller than the low-energy source types currently commercially available.
In accordance with an aspect of the present invention, the target technology
CA 022~6189 1998-12-1~
solutions used in the present invention are provided by either a fl.lidi7ed bed target holder
or a rotating tube target holder. Fluidized bed technology, whereby particulate material is
mixed while suspended or partially suspended against gravity on an upward flow of gas,
and rotating tube technology, whereby particulate material in a tube is mixed by tumbling,
are well known in fossil fuel combustion, powder ~ and particle coating
applications.
In accordance with a broad aspect of the present invention, there is provided a
general method of making radioactive sources by irradiating plt;rol-..ed seeds or other small
objects with a beam of light charged-particles. The said other small objects could include
encapsulated or coated objects, multi-layered objects, and small medical stents (such as
those described in U.S. Patent No. 5,176,617) which are made radioactive for medical
~.e~ related to duct and blood vessel patency. Any sources so made, if they are not
suitable for direct use, could be encapsulated (or further encapsulated) or coated after they
are made, depending on the nature of each source and its application. The nuclear reaction
utilized would depend upon the target element in the seeds or other small objects and upon
the type of irradiating particle employed. The target element in principle could be any one
of applox,.-lalely eighty stable natural elements but in practice would be chosen for its
chellLc.~l and physical properties to be amenable to the making of sources suitable for
particular purposes. The light charged-particles could be protons, deuterons or helium
nuclei. An t;~an~le of the general method is the irradiation of tit~ni~lm metal seeds with
helium-4 nuclei (commonly known as alpha particles) to make chromium-51 (halflife 28
days) sources via the nuclear reaction written as Ti4~(He-4,n)Cr-5 1.
In accordance with another broad aspect of the present invention, there is provided
a system for making radioactive sources. The system comprises a target holder for holding
2 5 a plurality of preformed non-radioactive seeds or other small objects. The target holder can
be ~ ç~ed to or placed inside of a charged-particle accelerator and is constructed at least
in part of a material that allows ~liln~ xion of a light chal~edp~ ~icle beam therethrough to
form a charged-particle window. The system also includes means for ~ g the seedsor other small objects in the target holder in a suitably dispersed state and means for cooling
the target holder, seeds or other small objects while receiving the beam of energetic
CA 022~6l89 l998- l2- l~
charged-particles through the charged-particle window.
In accordance with yet another broad aspect of the invention, there are providedpl~ro-l--ed non-radioactive seeds for use in making radioactive sources; which seeds
comprise at least in part a non-radioactive element or an alloy containing the element that is
tr~n~mllt~hle into a radioactive element by a light charged-particle beam.
In accordance with a specific aspect, the invention contemplates irradiation of
pr~roll..ed rhodium metal or rhodium alloy seeds with energetic protons from a
charged-particle accelerator. Different shapes and sizes of seeds and ~ le-l proton
energies in the 10 to 20 MeV range are used in order to optimize source production
efficiency and to oplil.. ~e source pe~ru-l-lallce with regard to various brachytherapy
applications. The nuclear reaction is Rh-103(p,n)Pd-103. The seeds are thereby directly
converted to p~ lm-103 sources. A~er irradiation, the sources require no furtheralteration before end-use.
The rhodium seeds are irradiated in batches of up to 10,000 units in one of two
types of target holder. Both types have means of sepa ~Ling the seed targets from the
accelerator vacuum system and of otherwise coping with the te~llnic.~l difficulties of the
irradiations. One ofthe target holders is a fllli~li7ed bed type which is preferred for making
elongated sources meant to have low self-shielding and is plt;rel~bly used in conjunction
with a vertically orientated, down-turned or up-turned proton beam. The other target
2 o holder is a rotating tube type and is preferred for making spherical sources, or low-intensity
sources of any shape where source self-~L-'1ing is not important. The rotating tube holder
may be used in conjunction with a proton beam of any directional orientation.
Thus the invention provides a new method and system for the large-batch
col.ll.-elcial production of radioactive sources, e.g. un-encapsulated p~ (lillm-103 sources
for interstitial brachytherapy. The benefits of the method and system relative to current
technology include: lower m~mlf~ctllring costs, greater source applications scope,
improved source radiation isotropy, and reduced source size.
CA 022~6189 1998-12-1~
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a cross-sectional view of an embodiment of a fl~ 7ed bed
charged-particle accelerator target holder in accordance with the present invention.
FIG. 2 is a cross-sectional view of an embodiment of a rotating tube
charged-particle accelerator target holder in accordance with the present invention.
FIGS. 3a and 3b are side-sectional and end-sectional views respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed is called a
solid line source.
FIGS. 4a and 4b are side-sectional and end-sectional views respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed is called an
X-beam source.
FIGS. 5a and 5b are side-sectional and end-sectional views respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed is called a
hollow line source.
FIGS. 6a and 6b are side-sectional and end-sectional views respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed may be
2 o described as an open tube source.
FIGS. 7a and 7b are side-sectional and end-sectional views respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed may is called
a dumb-bell source.
FIGS. 8a and 8b are a plan view and an edge elevation view respectively of a
rhodium metal or rhodium alloy seed. A source derived from this sort of seed is called a
platelet source.
FIG. 9 is a cross-sectional view of a rhodium metal or rhodium alloy seed. A
source derived from this sort of seed is called a solid sphere source.
FIG. l0 is a cross-sectional view of a rhodium metal or rhodium alloy seed. A
3 o source derived from this sort of seed is called a hollow sphere source.FIGS. l l is a side-sectional view of a seed formed by coating rhodium metal or
CA 022~6189 1998-12-1
rhodium alloy onto a suitable substrate in solid rod fomm. A source derived from this sort
of seed is called a coated line source.
DESCRIPTION OF SPECIFIC EMBODIMENTS
As ~i~cussed above, one aspect of the invention is an accelerator target holder
means for irradiating batches of seeds with light charged-particles of selected energy. This
energy is in the 10-20 MeV range when the charged particles are protons and the target
element in the seeds is rhodium. Two target holder embodiments are disclosed herein
below with reference to FIGS. I and 2.
Another aspect ofthe invention is a pl~rolllled seed, and in a preferred embodiment
the seed consists of rhodium metal. The seed can be in various shapes and designs such as
those shown in FIGS. 3 to 11 to meet various production and application requirements.
With reference to FIG. 1, a flllitli7ed bed target holder is shown in cross-section
containing a collective rhodium seed target 1 in relation to a down-tumed vertical beam of
protons 2. In order to make efficient use of the proton beam, the number of seeds in the
target and the packing density under operating fllli-li7ecl bed conditions must be sufficient to
e~f nti~lly fully intercept the beam. The fluidized bed target holder is the type pler~lled for
the irradiation of elongated seeds. It is of all metal construction and the body 3 is
2 o water-cooled 4 and made of a metal that is a good conductor of heat such as copper. The
seeds are inserted into and removed from the target cavity 5 through a channel 6 which is
plugged during the irradiation process. The insertion and removal of seeds is effected by
means of air pressure and suction respectively through a separate tube inserted into the
channel when needed. The target cavity may be plated with a suitable material such as
rhodium metal on those surfaces in contact with the seeds. The seeds are suspended
against gravity, in dynamic equilibrium on an upward flowing stream of inert gas 7 such as
helium or argon. The gas stream has the following functions: a) it continuously circulates
and occasionally inverts by turbulence the seeds within the target holder, on time scales that
are short relative to irradiation periods, so that all seeds are equally and symmetrically
exposed to the proton beam, thus providing consistency of radioactive characteristics
CA 022~6l89 l998- l2- l~
within a source batch; b) in the cases of elongated seeds, it supports the seedspredominantly in orientations that are at least approximately end-on to the beam, thereby
providing for small-angle or gl~nçing proton incidence on the sides of the seeds while
allowing relatively intense (per unit of surface area) exposure of the ends, thus positively
addressing the self-shielding and isotropic characteristics of the sources; and c) together
with the water-cooled metal body of the target holder, it removes the heat generated in the
seeds by the stopping of the proton beam, thus allowing for long irradiations without
source damage caused by over-heating of the seeds. This target holder also has provision
for sep~Lillg the seeds and gas stream from the beam line 8 vacuum 9 by means of a
cooled, thin window 10 that allows proton ~ n~ ion but disallows gas diffusion. The
window is composed of a mechanically strong, heat resistant and otherwise suitable
material such as rhodium metal foil or havar alloy foil. The window in the embodiment is a
double pane window that has inert gas such as helium or argon 11 flowing between the
panes for cooling and that is directly mounted on the target holder, as depicted in FIG. 1.
Alternatively, the window may have more spe~i~li7Pd means of rlic~ip~ting the heat
deposited in it by high current proton beams. For ~ ple, it may be part of an
independently rotating, or otherwise moving, meçh~ni~m dec,igned to present an
ever-rh~nging, cooled window surface to the proton beam. The proton beam currentin.pil~ g upon the target and target holder is measured through an electrical contact 12 on
2 o the target holder body.
A rotating tube target holder is shown in cross-section in FIG. 2 containing a
rhodium seed target 21 and in relation to a vertical, down-turned proton beam line 22. In
order to make efficient use of the proton beam, the number of seeds in the target and the
packing density under operating conditions must be sufficient to ecsP.nti~lly fully intercept
the beam. The tube 23 is constructed of a heat resistant and heat contlllcting metal with
acceptable meçh~nical, physical and chemical properties such as copper. It separates the
seeds from the accelerator vacuum system 24 and holds them in a thin walled section of the
tube, i.e. an annular window 25 section, that allows proton ~ n~",;~ion but disallows gas
diffusion through it. The window section may be an integral part of the tube or it may be a
3 o separate entity joined and vacuum-sealed to the main part of the tube. The window section
CA 022~6l89 l998- l2- l~
is also constructed of a heat resistant and heat con~ cting material with acceptable
mechanical, physical and chemical properties such as rhodium metal or havar alloy. A
continuous flow of inert gas 26 such as helium or argon is ~ ;"~ ed through the tube
during irradiations to carry away the heat deposited in the window section and in the target
seeds by the proton beam 27. The window in the embodiment is a single pane window that
is cooled by the same inert gas stream that cools the main body of the tube and the target
seeds. Alternatively, it may be double pane window and have an independent flow of inert
gas such as helium or argon between the panes for cooling. The tube is rotated so that the
seeds are efficiently mixed and tumbled to ensure equal and symmetric exposure to the
beam, and so that a freshly cooled window surface is continuously presented to the beam.
All seed types irradiated in the rotating tube holder receive çss~nti~lly isotropic illllmin~tion
by the proton beam. There is no me(~.h~ni~m to orientate elongated seeds in such a way that
they are pl er~ ially irradiated on the ends and at small angles of incidence on the sides.
The rotating tube holder is best suited to the irradiation of spherical seeds, or seeds of any
shape where source self-~lLel1ing is not an important factor.
In order to best achieve the objects of the invention, rhodium seeds of ~ elell~sizes and shapes are needed to achieve optimum pelrollllance with regard to m~mlf~ctllring
con~LI~ , source output intensity, source radiation distribution and brachytherapy
applications. Nine rhodium seed designs having a range of dimensions and shapes are
shown in FIGS. 3 to 11. These seeds of these embodiments are composed of rhodiummetal or rhodium alloy, or have rhodium metal coated upon a suitable substrate, and may
be m~mlf~ctllred by any suitable process. In source production situations, a batch of seeds
of applop.iate number, shape and size would be selected depending on requirements. This
batch comprises the target and is placed inside one of the target holders of FIGS. I and 2
2 5 ~tt~ched to an accelerator for proton irradiation.
The seed shown in FIGS. 3a and 3b yields a quasi line source (as opposed to a
theoretical line source, which has length but no thickness) that for present purposes is called
a solid line source. The seed itself is a solid rod of circular cross-section with hemispherical
ends. It may range in length from 1 to 10 millim~,t~rs and in rli~m~tlor from 0.2 to 1
millimP,tçrs, but it is elongated in form with a length/di~met~r ratio in the 2 to 20 range.
CA 022~6189 1998-12-1~
This seed is best irradiated in the fll~idi7ed bed target holder with a vertically oriented
proton beam. Under gas flow in this target holder, the suspended seed oscillates about a
more or less vertically aligned orientation most of the time. Since the proton beam is also
vertically orientated, this type of seed is pl~r~lel~ially irradiated on the ends 31, and the
protons striking the sides 32 do so at a small angle of incidence on the average. The design
therefore leads to improved isotropy since p~ ]m-103 production is favored at the ends
of the lon~itll~lin~l axis, thereby comp~n~ting for the depressed radiation output that
occurs at the ends of all real line sources with uniform radioactivity distributions. The
design also rliminiches source self-shielding by favoring small angles of proton incidence on
the sides of the seed, which means that pall~ m production close to the surface is favored.
The seed shown in FIGS. 4a and 4b also yields a quasi line source that is called here an
X-beam source. The seed itself is a solid rod with an X-shaped cross-section. It may range
in length from I to 10 millimP.t~rs with a maximum dimension on the cross-section ranging
from 0.2 to 1 millimPters, but it is elongated in form with a length/cross-section ratio in the
2 to 20 range. This seed is best irradiated in the fllli(1i~.ed bed target holder with a vertically
oriented proton beam. Under gas flow in this target holder, the seed oscillates about a
more or less vertically aligned orientation most of the time. Since the proton beam is also
vertically oriP.nt~te l, this type of seed is p~ ially irradiated on the ends 41, and the
protons striking the sides 42 do so at a small angle of incidence on the average. The design
thel~role leads to improved isotropy since p~ m-103 production is favored at the ends
of the longihlt1in~l axis, thereby compP.ns~ting for the depressed radiation output that
occurs at the ends of all real line sources with uniform radioactivity distributions. The
design also .1;",;~ hp~s source self-shielding by favoring small angles of proton incidence on
the sides ofthe seed, which means that p~ (lillm production close to the surface is favored.
The shape of this seed also allows for better cooling and for easier lowenergy photon
emergence, i.e. reduced source self-shielding.
The seed shown in FIGS. 5a and 5b yields another quasi line source called here ahollow line source. The seed itself is a hollow, thin-walled version of the seed shown in
FIGS. 3a and 3b and is best irradiated in the flllidi7ed bed target holder with a vertically
3 o oriented proton beam for the same reasons. It also has the same external dimension ranges
CA 022~6l89 l998- l2- l~
and much the same behavior and properties, although mef~h~nically it is not quite as sturdy.
Sources derived from it also have much the same properties with regard to isotropy and
self-slL~'1ing as the sources derived from the seed of FIGS. 3a and 3b because they are
similarly irradiated on the ends 51 and the sides 52. The wall 53 thickness is chosen to be a
depth in rhodium metal beyond which an unacceptably small fraction of the induced
palladium-103 low-energy photon radiation emerges. This wall thickness is in the range
0.025 to 0.075 millimet~rs. The seed is decigned for proton economy, since 10 to 20 MeV
protons pen~Ll~le rhodium metal to depths of 0.2 to 0.7 millim.?tlo.rs and ll~ler~ on the
average may interact with many of these hollow seeds as opposed to a much smaller
number of solid seeds of similar size and shape. The design of FIGS. 5a and 5b also has the
virtue of rhodium economy, rhodium being a rare and expensive metal.
The seed shown in FIGS. 6a and 6b yields another quasi line source called here an
open tube source. The seed itself is a thin-walled cylinder open at the ends. It may range in
length from 1 to 10 millimetf rs and in diameter from 0.2 to 1 millimçters, but it is Pl~ng~ted
in form with a length/(li~m~t~.r ratio is in the 2 to 20 range. This seed is best irradiated in
the fl~ 1i7~d bed target holder with a vertically oriented proton beam. Under gas flow in
this target holder, the seed oscillates about a more or less vertically aligned orientation most
of the time. The design of FIGS. 6a and 6b th~l~rul~ heS source self-shielding by
favoring small angles of proton incidence on the sides 61 of the seed, which means that
p~ (lillm production close to the surface will be favored. Isotropy of radiation output is
aided by more intense irradiation on the ends 62 and by photon radiation escaping from the
interior through the open ends. The wall thickness is chosen to be a depth in rhodium metal
beyond which an unacceptably small fraction of the induced p~ dillm-103 low-energy
photon radiation ~ ,es. This wall thickness is in the range 0.025 to 0.075 millimeters.
2 5 The seed is de~i~ned for proton economy, since 10 to 20 MeV protons penetrate rhodium
metal to depths of 0.2 to 0.7 millimeters and therefore on the average may interact with
many of these hollow seeds as opposed to a much smaller number of solid seeds of similar
external shape and dimensions. It also has the virtue of rhodium economy.
The seed shown in FIGS. 7a and 7b yields what is called here a dumb-bell source.The seed itself is a solid dumb-bell with a central rod 71 of circular cross-section
CA 022~6189 1998-12-1~
cormecting spherical ends 72. It may range in length from 1 to 10 millimet~rs and in
diameter from 0.2 to 1 millimlo.t~.rs, but it is elongated in form with a length/(li~m~.t~.r ratio in
the 3 to 20 range. Dumb-bell sources generaUy have better isotropy of output than real line
sources. This seed is best irradiated in the flllidi7çd bed target holder with a verticaUy
oriented proton beam. Under gas flow in this target holder, it osciUates about a more or
less verticaUy aligned orientation most of the time. Since the proton beam is also vertically
orientated, this type of seed wiU be p.~e~ iaUy irradiated on the ends 72. The design
the~ leads to further improved isotropy since p~ lm-103 production is favored atthe ends, and it is at the ends of the longit~1din~1 axis that radiation output is somewhat
depressed in a dumb-bell shaped source with uniform radioactivity distribution. Also, the
protons striking the rod section 71 will do so at a smaU angle of incidence on the average
and this will favor p~ 1illm 103 production near the surface and ~limini~h source
self-shielding.
The seed shown in FIGS. 8a and 8b yields what is caUed here a platelet source.
The seed itself is a rect~n~ r flat plate. Its dimensions may range as follows: length 1 to
10 millimeters, width 0.1 to 10 millimeters, and thickness 0.02 to 0.2 millimeters. It is
equally well irradiated using either a fluidized bed or a rotating tube target holder. Under
irradiation, both sides of the seed will be çc~f.nti~lly isotropically illllmin~ted by the proton
beam. The dimensions can be chosen so that source self- shielding is small. Sources made
2 o from such seeds may be used in groups to assemble larger sources of special properties or
for special applications.
The seed shown in FIG. 9 is a solid sphere and yields what is called here a solid
sphere source. The seed itself may range in diameter from 0.2 to 2 millimetP,rs. It is equally
well irradiated using either a flllidi7ecl bed or rotating tube target holder. Under irradiation,
it receives the same exposure to protons at all points on its surface. The induced
p~ illm-103 is symmetrically distributed and the low-energy photon radiation output is
almost perfectly isotropic. The curved surface favors small angles of proton incidence to
some extent which in turn (limini~hes self-shielding relative to what would be experienced in
the case of normal angle (90 degrees) irradiation of a flat thick target.
The seed shown in FIG. 10 is a hollow sphere and yields what is called here a
CA 022',6l89 l998-l2-l',
hollow sphere source. The seed itself may range in diameter from 0.2 to 2 millim~,t~,rs and
the wall thickness from 0,025 to 0,075 millim~t~.rs. It is equally well irradiated using either
a fluidized bed or rotating tube target holder. Under irradiation, it receives the same
exposure to protons at all points on its surface. The induced p~ m 103 is
symmetrically distributed and the low-energy photon radiation output is almost perfectly
isotropic, The curved surface favors small angles of proton incidence to some extent which
in turn ~ es self-shielding relative to what would be experienced in the case of normal
angle (90 degrees) irradiation of a fiat foil of id~.n~ic~l thickness, The wall thickness is
chosen to be a depth in rhodium metal beyond which an unacceptably small fraction of the
induced p~ rlillm-103 low-energy photon radiation will emerges. The seed is designed for
proton economy, since 10 to 20 MeV protons penetrate rhodium metal to depths of 0.2 to
0,7 millimeters and therefore on the average may interact with many of these hollow seeds
as opposed to a much smaller number of the solid spherical seeds. It also has the virtue of
rhodium economy.
The seed shown in FIG. 11 yields a quasi line source that for present purposes is
called a coated line source. The seed itself is a solid rod of circular cross-section with
hemispherical ends. It may range in length from 1 to 10 millim~.ters and in (li~metf~r from
0.2 to 1 millimeters, but it is elongated in form with a length/diameter ratio in the 2 to 20
range, The seed of FIG, 11 has a rhodium layer 111 coated upon a suitable substrate 1 12
such as titanium or one of the platinum group metals, the coating being done by
electroplating, chemical vapor deposition, physical vapor deposition or other suitable
means, The rhodium coating thickness lies in the range 0.01 millimeters to 0,2 millimeters,
This seed is best irradiated in the fluidized bed target holder with a vertically oriented
proton beam. Under gas flow in this target holder, the suspended seed oscillates about a
more or less vertically aligned orientation most of the time. Since the proton beam is also
vertically ori~.nt~te-l, this type of seed is pl~relell~ially irradiated on the ends 113, and the
protons striking the sides 114 do so at a small angle of incidence on the average, The
design therefore leads to improved isotropy since p~ (lillm-103 production is favored at
the ends of the longit~l~lin~l axis, thereby comp~n~ting for the depressed radiation output
that occurs at the ends of all real line sources with uniform radioactivity distributions, The
CA 022~6l89 l998- l2- l~
17
design also ~ ";~ l,es source self-shielding by favoring small angles of proton in~i(lence on
the sides ofthe seed, which means that p~ ]m production close to the surface is favored.
The design also favors rhodium economy and, depending on the substrate material, may
also be easier to fabricate than seeds which are of rhodium metal or alloy throughout.
EXAMPLE
A flllitli7ed bed target holder, such as that shown in FIG. 1, is ~ h~cl to a
down-tumed, vertical, evacl1~te(1, extemal, proton beam line of a cyclotron. The target
holder has connections to it: for cooling water to the body, for helium gas to start and
sustain the fluidized bed and to lll~ ;-l the seeds vertically orientated, for helium gas to
cool the target holder window, and an electrical connection to measure proton beam
current. Also, a sealable channel through the body to the target cavity allows seed delivery
through a tube by air pressure and source removal later by suction without (li~",~ g the
target holder.
A batch of e.g. 2000 rhodium seeds of the type called X-beam seeds, see FIGS. 4aand 4b, are delivered to the target seed cavity of the target holder. The cooling water and
the two helium flows are started at effective rates previously dele~ ed. The cyclotron is
started and the proton beam circulating within the cyclotron tank is developed to 0.5
milli~mperes of current. The stripping foil of the cyclotron is ~n~ged and the steering
magnets are adjusted to direct the beam down the beam-line and onto the target. The beam
is kept on target for 100 hours.
The energy of the protons in the beam line is 15 MeV. About 1 MeV is lost in
pen~Ll~ling the target holder window. This results in protons of about 14 MeV being
2 5 incident on the rhodium seeds. This is just above the apploxi.llaLely 12 MeV peak of the
Rh-103(p,n) Pd-103 excitation function, at which energy p~ m-103 production would
be at a maximum right at the surfaces of the seeds. However, at 14 MeV, the
p~ lm-l03 production rate is higher than at 12 MeV. Therefore a proton energy of 14
MeV is chosen as a colllp~ se with regard to the p~ (1illm-103 content of the sources
3 o and source self-shielding in order to optimize source radiation output.
CA 022~6l89 l998- l2- l~
18
Using 14 MeV protons on target, the p~ lm-103 production rate is about 200
millicuries per milli~mpere hour. In 100 hours of irradiation the overall production of
p~ m-103 is 200 x 0.5 x 100 = 10,000 millicuries. This would be equally divided
between 2000 sources, resulting in 5 millicuries per source. Because of self-shielding, the
effective output per source would be reduced to between 1 and 2 millicuries, which is a
very useful source strength range for brachytherapy applications.
After the irradiation is finished and a suitable period (less than 24 hours) haselapsed to allow short-lived radioisotopes to decay, the p~ lm-103 sources are removed
from the target holder to suitable facilities for quality assurance tests, assay, p~clr~ging and
distribution to medical centers.
Rhodium seeds of other shapes and construction and meant for conversion to
pAll~(lium-103 sources by direct proton irradiation are contemplated by the present
invention, in~luding ones that are made by coating or plating rhodium metal or rhodium
alloy on other materials, and ones that could be made as aggregates of smaller ones.
An aspect of the present invention also contemplates encapsulating the seed or
source with a human-tissue compatible substance that is at least substantially llanspal~-ll to
desired radioactive emissions. One such substance is titanium in f~l~m~nt~l, compound or
alloy form.
While the invention has been described in conjunction with specific embodiments
2 0 thereof, it is evident that many alternatives, modifications, and variations will be appa~ to
those skilled in the art in light of the foregoing description. Accordingly, it is int~n(led to
embrace all such alternatives, modification, and variations as fall within the spirit and broad
scope of the appended claims.
