WO1999033063A1

WO1999033063A1 - Method and system for making radioactive sources for interstitial brachytherapy and sources made thereby

Info

Publication number: WO1999033063A1
Application number: PCT/CA1998/001177
Authority: WO
Inventors: Robert Robertson
Original assignee: Robert Robertson
Priority date: 1997-12-19
Filing date: 1998-12-15
Publication date: 1999-07-01
Also published as: AU1745599A; CA2256189A1

Abstract

A specific embodiment provides preformed rhodium metal or rhodium alloy seeds that are directly converted to palladium-103 brachytherapy sources by irradiating them with energetic protons are disclosed together with means for manufacturing the sources in large numbers using special charged-particle accelerator target holders.

Description

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 manufacturing the small radioactive sources used in interstitial brachytherapy, and to the radioactive sources per se. Such sources are surgically implanted, either temporarily or permanently, in close proximity to diseased 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, meaning close or short).

Interstitial brachytherapy sources may be of solid, unitary construction and entirely composed of bio-compatible materials, or they may be composed of radioactive and other materials sealed inside bio-compatible capsules or coatings. Outwardly, they are usually metal cylinders with dimensions in the ranges: length 2 to 5 millimeters and diameter 0.2 to

1 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 contained by each sources can vary from 0.1 to 100 millicuries (mCi) but is usually in the range 0.5 to 10 mCi. For comprehensive information 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 different 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 manufacturing processes have correspondingly varied. Over the last few decades, most sources have been made by irradiating preformed, solid, unitary "seeds" with neutrons in nuclear reactors. (Note: finished interstitial brachytherapy sources ready for implant are often called seeds, but in this document the word seed is reserved for a preformed solid substrate which is not yet made radioactive to any de^ee, or is in the process of being made fully radioactive for purposes of making a finished brachytherapy source). This simple and economical 5 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 are generally employed as temporary implants. Although somewhat in decline because the energies of their emissions are now considered to be higher than desirable, iridium-192 o sources are still used in the largest numbers in interstitial brachytherapy.

Within the last ten years, other trends have become apparent. There are strong preferences developing in favor of permanent implant sources and radioisotopes emitting 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 5 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 diseased tissue region, as well as greatly reduced cumulative 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 o rate close to optimum with respect to therapeutic effect.

The two main low-energy sources in commercial supply, and now dominating 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 palladium- 103 (half-life 17 days) and iodine- 125 (half-life 60 days). Although 5 these sources types do possess the virtues delineated for low-energy sources in the preceding paragraph, both are far from ideal in other important aspects: a) the encapsulation material strongly attenuates 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 0 much more expensive and physically larger than the sources being displaced. These deficiencies stem largely from their designs and the constraints of their manufacturing methods.

There are two methods of making palladium- 103 preparations to serve as feed-stocks in commercial brachytherapy source manufacturing processes, where source 5 batch sizes are typically 100 to 10,000 units. The first method involves the irradiation of a palladium target with neutrons in a nuclear reactor, the target having been artificially enriched in the palladium- 102 isotope prior to the irradiation. The stable palladium- 102 nuclei capture neutrons to become radioactive palladium- 103 nuclei. The irradiation is followed by radio-chemical processing of the target. This results in a solution preparation o containing palladium- 103 with a specific activity that typically would be on the order of 100

Curies of palladium- 103 per gram of palladium, which is quite adequate for making brachytherapy sources.

The second method of producing palladium- 103 has largely supplanted the first method for commercial purposes. It involves the irradiation in high vacuum of a stationary 5 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 appropriate 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 0 milliampere 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 rhodiuml03 stable isotope atoms. Under irradiation, any 5 rhodium- 103 atom in the target and within the proton beam may capture a proton and essentially simultaneously eject one of its neutrons, thus forming a palladium- 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 palladium- 103 product within the rhodium target mass. Very little in the way of troublesome radioactive impurities are produced. 0 After the irradiation, the target is dissolved and the palladium- 103 is radio-chemically separated from the rhodium, which is usually recycled to make another target. The resulting palladium solution preparation could be essentially free of stable palladium atoms and could have a specific activity approaching the theoretical maximum value of about 75,000 Curies of palladium- 103 per gram of palladium. Usually, however, some natural palladium is deliberately added in the process, and the specific activity of the preparation is typically in the range 10 to 100 Curies per gram, similar to reactor-derived preparations.

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 summarize the technologies developed to date or formally envisioned for the commercial, large scale production of lowenergy brachytherapy sources based on palladium-103 and iodinel25. They involve sequential, labor and capital intensive processes which usually include the following steps: a) separate manufacturing of radioisotope preparations entailing irradiations and radio-chemical operations; b) loading portions of the radioisotope preparations 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 metal capsules, or 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 palladium-103 sources in large batches by a simple and economical method which avoids radio-chemical operations, encapsulations and associated costs and product problems. One embodiment is effected by irradiating a batch of preformed 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 palladium-103 production and the nuclear reaction is the same, as outlined above. The method is feasible because: a) rhodium and palladium metals are members of the platinum group of inert, bio-compatible 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 palladium-103 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 palladium-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 1 to 2 square centimeters. Because protons carry an electric charge, they do not easily penetrate 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 successful outcome in the sense of yielding finished sources having approximately equal amounts of palladium-103 radioactivity distributed in an equivalent and suitably symmetric way within each source. The protons would barely penetrate the first layer of seeds, and even in these the resulting palladium-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 0.1 to I milliampere to yield an adequate palladium-103 production rate for commercial purposes. The beam power would be expected, therefore, to be typically in the range 1-20 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. Palladium-103 has very 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, including 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 palladium-103. Protons with energies in this range penetrate rhodium metal to a depth of 0.2 to 0.7 millimeters. 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 palladium-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 palladium-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 palladium-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 palladium-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 palladium-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 palladiuml03 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 palladiuml03 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 solutions used in the present invention are provided by either a fluidized 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 treatment 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 preformed 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 treatments 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 approximately eighty stable natural elements but in practice would be chosen for its chemical 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 example of the general method is the irradiation of titanium 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 Ti48(He-4,n)Cr-51.

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 a plurality of preformed non-radioactive seeds or other small objects. The target holder can be attached to or placed inside of a charged-particle accelerator and is constructed at least in part of a material that allows transmission of a light chargedparticle beam therethrough to form a charged-particle window. The system also includes means for maintaining the seeds or 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 charged-particles through the charged-particle window.

In accordance with yet another broad aspect of the invention, there are provided preformed 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 transmutable into a radioactive element by a light charged-particle beam.

In accordance with a specific aspect, the invention contemplates irradiation of preformed rhodium metal or rhodium alloy seeds with energetic protons from a charged-particle accelerator. Different shapes and sizes of seeds and different proton energies in the 10 to 20 MeV range are used in order to optimize source production efficiency and to optimize source performance with regard to various brachytherapy applications. The nuclear reaction is Rh-103(p,n)Pd-103. The seeds are thereby directly converted to palladium-103 sources. After irradiation, the sources require no further alteration 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 separating the seed targets from the accelerator vacuum system and of otherwise coping with the technical difficulties of the irradiations. One of the target holders is a fluidized bed type which is preferred for making elongated sources meant to have low self-shielding and is preferably used in conjunction with a vertically orientated, down-turned or up-turned proton beam. The other target holder is a rotating tube type and is preferred for making spherical sources, or low-intensity sources of any shape where source self-shielding 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 commercial production of radioactive sources, e.g. un-encapsulated palladium-103 sources for interstitial brachytherapy. The benefits of the method and system relative to current technology include: lower manufacturing costs, greater source applications scope, improved source radiation isotropy, and reduced source size. BRIEF DESCRIPTION OF THE DRAWINGS

5 FIG. 1 is a cross-sectional view of an embodiment of a fluidized 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 0 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. 5 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 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 5 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. 10 is a cross-sectional view of a rhodium metal or rhodium alloy seed. A o source derived from this sort of seed is called a hollow sphere source.

FIGS. 11 is a side-sectional view of a seed formed by coating rhodium metal or rhodium alloy onto a suitable substrate in solid rod form. A source derived from this sort of seed is called a coated line source.

DESCRIPTION OF SPECIFIC EMBODIMENTS

As discussed 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. 1 and 2.

Another aspect of the invention is a preformed 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 fluidized bed target holder is shown in cross-section containing a collective rhodium seed target 1 in relation to a down-turned 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 fluidized bed conditions must be sufficient to essentially fully intercept the beam. The fluidized bed target holder is the type preferred for the irradiation of elongated seeds. It is of all metal construction and the body 3 is 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 within a source batch; b) in the cases of elongated seeds, it supports the seeds predominantly in orientations that are at least approximately end-on to the beam, thereby providing for small-angle or glancing proton incidence on the sides of the seeds while allowing relatively intense (per unit of surface area) exposure of the ends, thus positively 5 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 separating the seeds and gas stream from the beam line 8 vacuum 9 by means of a 0 cooled, thin window 10 that allows proton transmission 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. 5 Alternatively, the window may have more specialized means of dissipating the heat deposited in it by high current proton beams. For example, it may be part of an independently rotating, or otherwise moving, mechanism designed to present an ever-changing, cooled window surface to the proton beam. The proton beam current impinging upon the target and target holder is measured through an electrical contact 12 on 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 essentially fully intercept 5 the beam. The tube 23 is constructed of a heat resistant and heat conducting metal with acceptable mechanical, 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 transmission but disallows gas diffusion through it. The window section may be an integral part of the tube or it may be a o separate entity joined and vacuum-sealed to the main part of the tube. The window section is also constructed of a heat resistant and heat conducting 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 maintained 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 essentially isotropic illumination by the proton beam. There is no mechanism to orientate elongated seeds in such a way that they are preferentially 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-shielding is not an important factor.

In order to best achieve the objects of the invention, rhodium seeds of different sizes and shapes are needed to achieve optimum performance with regard to manufacturing constraints, 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 rhodium metal or rhodium alloy, or have rhodium metal coated upon a suitable substrate, and may be manufactured by any suitable process. In source production situations, a batch of seeds of appropriate 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 attached 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 millimeters and in diameter from 0.2 to 1 millimeters, but it is elongated in form with a length/diameter ratio in the 2 to 20 range. 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 orientated, this type of seed is preferentially 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 palladium-103 production is favored at the ends of the longitudinal axis, thereby compensating for the depressed radiation output that occurs at the ends of all real line sources with uniform radioactivity distributions. The design also diminishes source self-shielding by favoring small angles of proton incidence on the sides of the seed, which means that palladium 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 millimeters with a maximum dimension on the cross-section ranging from 0.2 to 1 millimeters, 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 fluidized 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 orientated, this type of seed is preferentially 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 therefore leads to improved isotropy since palladium-103 production is favored at the ends of the longitudinal axis, thereby compensating for the depressed radiation output that occurs at the ends of all real line sources with uniform radioactivity distributions. The design also diminishes source self-shielding by favoring small angles of proton incidence on the sides of the seed, which means that palladium 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 a hollow 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 fluidized bed target holder with a vertically oriented proton beam for the same reasons. It also has the same external dimension ranges and much the same behavior and properties, although mechanically it is not quite as sturdy. Sources derived from it also have much the same properties with regard to isotropy and self-shielding 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 millimeters. 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 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 millimeters and in diameter from 0.2 to 1 millimeters, but it is elongated in form with a length/diameter ratio is in the 2 to 20 range. 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 seed oscillates about a more or less vertically aligned orientation most of the time. The design of FIGS. 6a and 6b therefore diminishes source self-shielding by favoring small angles of proton incidence on the sides 61 of the seed, which means that palladium 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 palladium-103 low-energy photon radiation emerges. This wall thickness is in the range 0.025 to 0.075 millimeters. 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 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. 0 The seed itself is a solid dumb-bell with a central rod 71 of circular cross-section connecting spherical ends 72. It may range in length from 1 to 10 millimeters and in diameter from 0.2 to 1 millimeters, but it is elongated in form with a length/diameter ratio in the 3 to 20 range. Dumb-bell sources generally have better isotropy of output than real line sources. This seed is best irradiated in the fluidized bed target holder with a vertically oriented proton beam. Under gas flow in this target holder, it 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 will be preferentially irradiated on the ends 72. The design therefore leads to further improved isotropy since palladium-103 production is favored at the ends, and it is at the ends of the longitudinal 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 small angle of incidence on the average and this will favor palladium-103 production near the surface and diminish source self-shielding.

The seed shown in FIGS. 8a and 8b yields what is called here a platelet source. The seed itself is a rectangular 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 essentially isotropically illuminated by the proton beam. The dimensions can be chosen so that source self- shielding is small. Sources made 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 millimeters. 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 palladium-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 diminishes 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 hollow sphere source. The seed itself may range in diameter from 0.2 to 2 millimeters and the wall thickness from 0.025 to 0.075 millimeters. 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 palladium-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 diminishes self-shielding relative to what would be experienced in the case of normal angle (90 degrees) irradiation of a flat foil of identical thickness. The wall 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 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 millimeters and in diameter 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 112 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 orientated, this type of seed is preferentially 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 palladium-103 production is favored at the ends of the lon^tudinal axis, thereby compensating for the depressed radiation output that occurs at the ends of all real line sources with uniform radioactivity distributions. The design also diminishes source self-shielding by favoring small angles of proton incidence on the sides of the seed, which means that palladium 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 fluidized bed target holder, such as that shown in FIG. 1, is attached to a down-turned, vertical, evacuated, external, 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 maintain the seeds vertically orientated, for helium gas to cool the target holder window, and an electrical connection to measure proton beam current. Also, a scalable channel through the body to the target cavity allows seed delivery through a tube by air pressure and source removal later by suction without dismantling the target holder.

A batch of e.g. 2000 rhodium seeds of the type called X-beam seeds, see FIGS. 4a and 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 determined. The cyclotron is started and the proton beam circulating within the cyclotron tank is developed to 0.5 milliamperes of current. The stripping foil of the cyclotron is engaged 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 penetrating the target holder window. This results in protons of about 14 MeV being incident on the rhodium seeds. This is just above the approximately 12 MeV peak of the

Rh-103(p,n) Pd-103 excitation function, at which energy palladium-103 production would be at a maximum right at the surfaces of the seeds. However, at 14 MeV, the palladium-103 production rate is higher than at 12 MeV. Therefore a proton energy of 14 MeV is chosen as a compromise with regard to the palladium-103 content of the sources and source self-shielding in order to optimize source radiation output. Using 14 MeV protons on target, the palladium-103 production rate is about 200 millicuries per miUiampere hour. In 100 hours of irradiation the overall production of palladium-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) has elapsed to allow short-lived radioisotopes to decay, the palladium-103 sources are removed from the target holder to suitable facilities for quality assurance tests, assay, packaging and distribution to medical centers.

Rhodium seeds of other shapes and construction and meant for conversion to palladium-103 sources by direct proton irradiation are contemplated by the present invention, including 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 transparent to desired radioactive emissions. One such substance is titanium in elemental, compound or alloy form.

While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modification, and variations as fall within the spirit and broad scope of the appended claims.

Claims

What is claimed is:

1. A method of making radioactive sources comprising of: inserting a plurality of preformed non-radioactive seeds or other small objects into a target holder, said seeds or small objects being formed at least in part of a non-radioactive element transmutable into a

5 radioactive element by means of a beam of energetic light charged-particles; and irradiating the seeds or other small objects with a beam of energetic light charged-particles, said light charged-particles being either protons, or deuterons, or helium-3 nuclei, or helium-4 nuclei.

2. The method of claim 1 wherein said radioactive sources are meant for use in interstitial brachytherapy, said light charged-particles are protons, said non-radioactive o element is pure rhodium, and said radioactive element is palladium- 103.

3. The method of claim 2 wherein said pure rhodium is alloyed with at least one element or compound.

4. The method of claim 1 wherein a charged-particle accelerator generates said beam of light charged-particles.

5 5. The method of claims 2 and 3 wherein a charged-particle accelerator generates said beam of protons.

6. The method of claims 2 and 3 wherein each one of said radioactive sources is: from 1 millimeters to 10 millimeters in length and from 0.2 millimeters to 1 millimeter in maximum cross sectional dimension in the case of an elongated source; from 0.2 o millimeters to 1 millimeter in diameter in the case of a spherical source; from 1 millimeter to

10 millimeters in length, from 0.1 millimeters to 10 millimeters in width, and from 0.02 millimeters to 0.2 millimeters in thickness in the case of a rectangular platelet source; and has a rhodium or rhodium alloy coating ranging in thickness from 0.01 millimeters to 0.2 millimeters in the case of a rhodium coated source. 5 7. The method of claims 2 and 3 wherein each one of said radioactive sources contains an amount of palladium-103 radioactivity in the range from 0.1 millicuries to 100 millicuries.

8. A system for making radioactive sources comprising: a target holder for holding a plurality of preformed nonradioactive seeds or other small objects, said target 0 holder being constructed at least in part of a material that transmits a beam of energetic light charged-particles therethrough to form a charged-particle window; said seeds or other small objects being formed at least in part of a non-radioactive element transmutable into a radioactive element by a light charged-particle beam; said light charged-particles being either protons, or deuterons, or helium-3 nuclei, or helium-4 nuclei; means for maintaining the seeds or other small objects in the target holder in a dispersed and cooled state; and means for directing the beam of energetic light charged particles through the target holder window to irradiate the dispersed seeds or other small objects and transmute the non- radioactive element therein into a radioactive element and thereby convert the seeds or other small objects into radioactive sources.

9. The system of claim 8 wherein said target holder is of the fluidized bed type.

10. The system of claim 8 wherein said target holder is of the rotating tube type.

11. The system of claim 8 wherein said radioactive sources are meant for use in interstitial brachytherapy, said light charged-particles are protons, said non-radioactive element is rhodium, and said radioactive element is palladium-103.

12. The system of claim 8 wherein a charged-particle accelerator generates said beam of energetic light charged particles.

13. The system of claim 11 wherein each one of said radioactive sources is: from 1 millimeters to 10 millimeters in length and from 0.2 millimeters to 1 millimeter in maximum cross sectional dimension in the case of an elongated source; from 0.2 millimeters to 1 millimeter in diameter in the case of a spherical source; and from 1 millimeter to 10 millimeters in length, from 0.1 millimeters to 10 millimeters in width, and from 0.02 millimeters to 0.2 millimeters in thickness in the case of a rectangular platelet source; and has a rhodium or rhodium alloy coating ranging in thickness from 0.01 millimeters to 0.2 millimeters in the case of a rhodium coated source.

14. The system of claim 11 wherein each one of said radioactive sources contains an amount of palladium-103 radioactivity in the range from 0.1 millicuries to 100 millicuries.

15. A preformed stable seed consisting essentially of rhodium or an alloy containing rhodium where the rhodium component is transmutable into palladium-103 by a proton beam to directly yield a radioactive source containing a therapeutic amount of palladium-103 radioactivity ready for implantation for application in interstitial brachytherapy.

16. The method of claim 1 wherein the seeds are nonradioactive.

17. A method of making radioactive sources for use in interstitial brachytherapy comprising the steps of: inserting a plurality of preformed stable seeds in a chamber constructed at least in part of a material that transmits a beam of energetic light charged-particles therethrough to form a window for said beam; said sources being formed at least in part of a stable element transmutable into a radioactive element by said beam; and maintaining said sources in said chamber in a dispersed state while said beam is directed through said window to irradiate the dispersed sources and transmute the stable element in each source into a radioactive element.

18. The method of claim 1 wherein said stable element is rhodium and said radioactive element is palladium- 103.

19. A system for making radioactive sources for use in interstitial brachytherapy comprising: a chamber for holding a plurality of preformed stable sources, said chamber being constructed at least in part of a material that transmits a beam of energetic light charged particles therethrough to form a window for said beam, said sources being formed at least in part of a stable element transmutable into a radioactive element by said beam; means for maintaining said sources in said chamber in a dispersed state; and means for directing said beam through said window to irradiate the dispersed sources and transmute the stable element in each source into a radioactive element.